1-aklil, 1 alkenyl or 1-alkynylaryl-2-amino-1,3 - propandiol or their optical isomers, or pharmaceutically acceptable salts and method of production thereof

 

(57) Abstract:

Usage: as medicines for the treatment of memory disorders. Essence: 1-alkyl, 1-alkenyl or 1-alkynylaryl-2-amino-1,3-propandiol receive, for example, the interaction of halogenpoeten with fenilalanina in the acid acceptor and in the presence dichloride bis(triphenylphosphine) palladium/copper iodide at 0 - 75oC. 2 C. p. F.-ly, 4 Il., 7 table.

The invention relates to 1-alkyl, 1-alkenyl, and 1-alkynylaryl-2-amino-1,3-propandiol formula 1:

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where R is

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< / BR>
R5represents a group of the formula:

CH3(CH2)mCC, CH3(CH2)mCH CH-,

CH3(CH2)mCH2-CH2-,

,

m is from 3 to 15 and n is from 0 to 12.

R1is hydrogen or where R6hydrogen, lower alkyl, lower alkoxy, or R2is hydrogen or lower alkyl, R3is hydrogen, lower alkyl, or where R6defined above,

R4is , where R7hydrogen, lower alkyl, or CH2OR6where R6hydrogen or , where R6defined above,

R1and R8taken together with the oxygen atom to which they are attached, form a group of the formula:

The present invention relates also to the optical isomers of these compounds or their pharmaceutically acceptable salts, and the use of these compounds for the treatment of inflammatory conditions /because they have the ability to inhibition of protein kinase C/; for the treatment of psoriasis and other skin diseases; for the treatment of cancer /because these compounds are capable of inhibiting the growth of tumor cells/; for the treatment of memory disorders, such as Alzheimer's disease, as well as antifungal and antibacterial agents that can be used both separately and in combination with adjuvantly.

Preferred 2-amino-1,3-propandiol of the present invention are compounds in which R is , R1, R2and R3are hydrogen and R5is CH3/CH2/mCH2CH2or CH2/CH2/nCH2CH2. Preferred are compounds where R is a ; R1and R2the hydrogen ; and R5CH3/CH2/m.

Compounds of the present invention, in which there is no element of symmetry exist in Kasich racemic forms by standard optical separation, including, for example, separation diastereomeric salts of the compounds, which are characterized by the presence of the basic amino group and an optically active acid; or compounds which are characterized by the presence of carboxylic acid group and an optically active base, or by synthesis of their optically active precursors.

The present invention includes all optical isomers, racemic forms, and geometric isomers, which will be disclosed in the description to the claims. Formulas of the compounds presented in the present description, show that they include all possible geometrical and optical isomers.

Compounds of the present invention, having contiguous chiral centers are present as diastereoisomers and vary as Erythro - and treasurery. Erythro-diastereomers are such compounds that can be mesoporous, that is optically inactive form due to the fact that they have an element of symmetry in one of the possible conformations, if one of the different substituents substituted for one another. Tradestream are such compounds that remain enantiomer, i.e., optically active isometrically to be replaced by another. For example, the substitution of amino Erythro-2-amino-1,3-propane diol 9a of the present invention hydroxyl group forms a meso-1,2,3 - propantriol 9b, having a plane of symmetry passing through the carbon skeleton of the molecule, as shown below:

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and the substitution of the amino threo-2-amino-1,3-propane diol 9c of the present invention hydroxyl group forms an enantiomer 9d, in which the symmetry element in all conformations, one of which is represented by the formula 9d.

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New 1-alkyl-, 1-alkenyl - or 1-quinil-aryl-2-amino-1,3 - propandiol General formula I can be obtained by reaction of the compound of formula 4A

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where R" is

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R11and R12lower alkyl, Y is halogen, with Alcina formula or

CH3(CH2)mCCH

where m and n are defined above, to obtain the compounds of formula I, where R is defined above, where R5group or

CH3(CH2)mCC

R1and R2hydrogen, R3the group COR6where R6lower alkyl, and R4group CO2R7where R7lower alkyl, with or subsequent allocation of the target product, or b) not necessarily recover the alkali metal borohydride to obtain the connection forms of the R3the group COR6where R6lower alkyl, and R4is a group CH2OH, or C) the optional hydrogenation of the compounds of formula I, obtained in stage a) or b), in order to obtain the compounds of formula I, where R is defined above, where R5is CH3(CH)2mCH2-CH2or , CH2-CH2, R1and R2are hydrogen, R3is COR6where R6lower alkyl and R4is the CO2R7where R7lower alkyl, or R4is CH2OH, or d) optionally recovering the compounds of formula I, where R is defined above, where R5is CH3(CH2)mCH2-CH2or

< / BR>
CH-CH2, R1and R2are hydrogen, R3is COR6where R6lower alkyl, and R4is the CO2R7where R7lower alkyl, with the use of alkaline borohydride in order to obtain the compounds of formula I, where R, R5, R1and R2defined above, and R4is CH2OH, or

e) the optional hydrogenation of the compounds of formula I in which R is defined above, where R5is or-CH3(CH2)mCC R1and R2are hydrogen, R3is I, where R, R1, R2, R3and R4defined above and R5is CH3(CH2)mCH CH or CH CH or f) optional hydrolysis of the compounds of formula I, where R is defined above, R1and R2is hydrogen, R3is COR6where R6lower alkyl and R4is CH2OH in order to obtain the compounds of formula I, where R, R5, R1and R4defined above, and R3is hydrogen, or

g) optional interaction of the compounds of formula I, where R is defined above, R1, R2and R3are hydrogen, and R4is CH2OH, with a lower aldehyde in the presence of a reducing agent to obtain compounds of the formula I, where R and R5defined above, R2is hydrogen, R4is CH2OH and R2and R3are lower alkyl, or

h) optional interaction of the compounds of formula I, where R is defined above, R1, R2and R3are hydrogen and R4is-CH2OH with N-benzyloxycarbonyloxy-succinimido formula 20:

< / BR>
in order to obtain the compounds of formula I, where R and R5defined above, R1and R2are benzyloxycarbonyl, R2- bodoro what Finance the compounds of formula I, where R is defined above, R1and R2are hydrogen, R3is COR6where R6lower alkyl, and R4is CH2OH in order to obtain the compounds of formula I, where R, R5, R1, R2and R3defined above, and R4is CH2OCOR6where R6lower alkyl, or

l) optional interaction of the compounds of formula I, where R is defined above, R1and R2are hydrogen, R3is COR6where R6lower alkyl, and R4is CH2OH with 2,2-dimethoxypropane, in order to obtain the compounds of formula I, where R, R2and R3defined above, R4CH2OR8and R1and R8taken together form a group of the formula:

< / BR>
A common way to obtain a new 1-alkyl-, 1-alkenyl, and 1-alkynylaryl-2-amino-1,3-propanediols of the present invention may be derived are illustrated by the Reaction schemes a, b and C (Fig.1-3) for a number of pyridines having aracelio side chain. These transformations can be used to obtain compounds of the present invention, in which aryl group, among others, is substituted and unsubstituted phenyl, furyl, thienyl, isoxazolyl, isothiazolin, and pyrrolyl, t is s 1-alkylpyridinium-2-amino-1,3-propane diol 7, where W and X are hydrogen, alkyl, alkoxy, halogen or trifluoromethyl, pyridinecarboxamide 2, in which W and X are defined above and Y is halogen, condense complex ether of aminomalonate acid 3, where R11and R12are alkyl, in order to obtain pyridinylamino 4, where R11and R12X and Y are defined above, which alkynylaryl to obtain alkylpyridine 5, where R11, R12, W, and X are defined above, n 3 15, which in turn reduced to the pyridinyl-1,3-propane diol 6, where R12and X is defined above, and then hydrolyzing to compound 7.

Condensation carboxaldehyde 2 and malonate 3 is conducted in an ether solvent in the presence of a tertiary amine. Examples of such solvents may be diethyl ether; 1,2-dimethoxyethane, 2-methoxyethylamine ether, dioxane, and tetrahydrofuran. Examples of the tertiary amines can be pyridine /pyridine, picoline, lutidine and kallidin/ and trialkylamine /trimethylamine, triethylamine, Tripropylamine/. The preferred solvent is tetrahydrofuran, and the preferred tertiary amine is triethylamine. Since the condensing temperature is not critical, the reaction is preferably Osumi low temperatures near 0 25oC/, and at elevated temperature from about 25oC to the boiling point of the reaction mixture/.

The reaction alkilirovanija carried out by processing halogenpoeten 4 Alcina 13:

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where W and n are defined above in the acid acceptor, for example, di - or trialkylamine, such as dietician, dipropylamine, trimethylamine, or Tripropylamine, and in the presence dichloride bis/triphenylphosphine/palladium/copper iodide at a temperature of about 0 75oC. the Preferred acid acceptor is triethylamine. The preferred temperature of the alkylation temperature is about 50 to 60oC. there may be used ether solvent. Such ethereal solvents are diethyl ether, 1,2-dimethoxyethane, 2-methoxyethylamine ether, dioxane, and tetrahydrofuran. The preferred solvent is tetrahydrofuran.

Response recovery alkylarylsulphonate 5 in propandiol 6 is carried out using alkaline borohydride in an ether solvent at a temperature recovery in the range of about 0 50oC. Such borohydride alkali metals are borohydride calcium, borohydride lithium, borohydride potassium and borohydride sodium. As examples of the ether dissolve titelnoj is a recovery of lithium borohydride or calcium borohydride in tetrahydrofuran at a temperature of about 0 25oC.

Hydrolysis carboxamide 6 in aminodiol 7 can be implemented using standard hydrolysis technique. For example, carboxamid 6 can be gidrolizirovanny using a hydroxide of an alkali metal, e.g. lithium hydroxide, sodium or potassium, in an aqueous alkanol, such as methanol, ethanol or 1 - or 2-propanol, at a temperature of hydrolysis of about 0 100oC.

In order to obtain 1-alkylpyridinium-2-amino-1,3-propane diol 9, where W, X and m are defined above, 1-alkylpyridinium-2-amino-1,3 - propandiol 6, hydrogenizing obtaining 1-alkylpyridinium-2 - amido-1,3-propane diol 8, which is converted into 1-alkylpyridinium-2 - amino-1,3-propandiol 9.

The hydrogenation is carried out by treatment of alkyne 6 hydrogen at atmospheric pressure of approximately 60 psi /to 413.6 kPa/, and preferably about 40 pounds/square inch /275,7 kPa/ in the presence of a metal catalyst, e.g. platinum, palladium, rhodium or ruthenium catalyst without substrate or deposited on a substrate made of carbon or calcium carbonate, is preferred is palladium carbon, and in the presence of alkanol, for example, methanol, ethanol, or 1 - or 2-propanol, preferably ethanol, at americamiddle 8 pyridinylmethyl 9, that is, hydrazines 8, is carried out with the use of hydrazine in free or hydrated form, in alkanol, for example, such as methanol, ethanol or 1 - or 2-propanol, at a temperature of from about 25oC to the temperature of the distillation of the reaction mixture. The preferred solvent is ethanol. Temperature hydrazinolysis preferably is a distillation temperature of the reaction mixture.

Alternatively, the receiving systems 1-quinil - and 1-alkylpyridinium-2-amino-1,3-propane diol, that is, systems of formulas 7 and 9, respectively, where W, X and n are defined above, can be achieved by alkilirovanija of pyridinecarboxamide 2, where W, X and Y are defined above, in alkylphenolethoxylate 10, where W, X and m are defined above, followed by conversion of pyridinecarboxamide 10 pyridinylamino 5, where R11, R12, W, X and m are defined above, and hydrogenation of alkylpyridine 5, where R11, R12, W, X and m are defined above in connection 11, where R11, R12, W, X and m are defined above. Reaction alkilirovanija, conversion and hydrogenation, that is, the transformation of 2 to 5 and 11 through 10, provide means basically the same as the corresponding transformations of 4 to 5, 2 to 4 and 6 to 8.

-alkyl pyridinylmethyl 8 way, basically, the same method used for recovery of alkylarylsulphonate 5 in propandiol 6.

A number of 1-alkylpyridinium-2-amino-1,3-propane diol, that is, a series of compounds represented by formulae 5, 6 and 7 can also be achieved by restoring alkylarylsulphonate 4, where R11, R12, W, X and Y are defined above, in pyridinylmethyl 12, and alkilirovanija thus obtained peridiniidae 12 in alkylpyridinium 6. As mentioned above, aminopropanol 6 turn in aminopropanol 7 by hydrolysis. Similarly, the recovery of 4 in 12 and alkilirovanie 12 6 do basically the same way as the one that was used for the conversion of 5 and 6, and 4 to 5.

Derivative alkylpyridinium-2-amino-1,3-diol 7 is obtained from aminopropanol 6 by acylation of 6, where R12, W, X and m are defined above, in aminodeacetoxy 15, where R12, R13, R14W and m are defined above, using, for example, anhydride alanovoy acid, such as acetic anhydride, in the presence of triethylamine and 4-dimethylaminopyridine and dioxanonane 6 in aminodeoxy 14, where R12, R15, R16, W, X and m are defined above, using the W conversion of 6 to 7/ receive aminopropanol 7. Aminodeacetoxy 15 is subjected to selective hydrolysis with getting aminodiphenylamine 20, for example, by using a carbonate of an alkali metal such as lithium carbonate, sodium or potassium, in alkanol, such as methanol, ethanol or 2-propanol. The preferred medium for hydrolysis is potassium carbonate in methanol. Hydrolysis process usually proceeds at room temperature. You can also use and elevated temperature up to the temperature of the distillation of the hydrolysis mixture.

Allowee derivatives aminopropanol 12, where R12X and Y are defined above, are obtained by processing 12 anhydride alanovoy acid under the same conditions described for the conversion of 6 to 15.

In order to obtain 1-alkenyl-2-amino-1,3-propane diol 17, where W, X and m are defined above, 1-quinil-2-amino-1,3-propandiol 6, where R12, W, X and m are defined above, hydrogenizing to obtain 1-alkenyl-2-amino-1,3-propane diol 16, where R12, W, X and m are defined above, and the configuration of hydrogen atoms in the double bond carbon-carbon is a CIS-configuration, which, in turn, hydrolyzing 17, where W, X and m are defined above.

To obtain N,0,0 tribenzylamine-2-amino-1,3 - propane 18, where R15I tertiary amine, for example, triethylamine in ether solvent such as tetrahydrofuran, at about room temperature.

For the synthesis of 2-amino-1,3-propane diol 19, 1,3-decyloxy-2 - propylacetamide 13 hydrolyzing using hydrazine hydrate is added in the presence of ethanol according to the procedure described for the conversion of 8 to 9.

Typically, the final 1-alkylaryl-2-amino-1,3-propandiol of the present invention is obtained from 1-alkenylcarbazoles. Cm. The reaction scheme for the conversion of 10 9 the pyridine series. In isoxazolone the series, the final 1-acilitator-2-amino-1,3-PROPANEDIOL can be obtained, for example, from 5-/1-alkyl/-3-isoxazolecarboxylic 21, where R5dodecyl.

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3-isoxazolecarboxylic 21, where R5is dodecyl, in turn, synthesize, for example, by condensation of 1-nitratireducens 0-trimethylsilylpropyne in the presence of phenylisocyanate and triethylamine, and then tetrabutylammonium fluoride, resulting in a gain isoxazolidine 22

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where R5is dodecyl, which can be oxidized to 21 with oxalicacid: dimethyl sulfoxide.

To obtain 2-alkoxycarbonyl-1,3-propane diol, e.g shall kinil-2-amino-1,3-propandiol 7 acelerou with di-t-BUTYLCARBAMATE in the presence of a base, such as sodium bicarbonate in halogenougljovodonika a solvent such as chloroform, at a high temperature of about 60oC.

To obtain 2-dialkylamino-1,3-propane diol, for example, 1 alkenyl-2-dimethylamino-1,3-propane diol 23, 1 alkenyl-2-amino - 1,3-propandiol 17 is subjected to reductive alkylation with formaldehyde, such as formalin, in the presence of a reducing agent, such as cyanoborohydride sodium in a solvent such as acetonitrile, at room temperature.

1 alkenyl-2-amino-1,3-propandiol, for example, 1-alkenylphenol-2-amino-1,3-propandiol 17, obtained by reduction reaction of 1-alkylpyridinium-2-acylamino-1,3 - propane diol 6 through 1 alkenyl-2-acylamino-1,3-propane diol 16 /see Reaction scheme/. Alternative 1 alkenyl-2-amino-1,3-propandiol, for example, 1-alkenylacyl-2-amino-1,3-propandiol 27 can be obtained by condensation of halogenlithiumcarbenoid 25, where X is bromine, with tri-n-butyl-1-alkenylsilanes 24 in the presence of 2,6-di-t-butyl-4-methyl-phenol and tetrakis /triphenylphosphine/ palladium /O/ in an aromatic solvent such as toluene, at room temperature to obtain 1-alkenylhydroperoxides 26 (see Fig.4/, the cat is x And, B and C.

Target tri-n-butyl-1-alkenylsilanes 24 is obtained by reductive condensation of alkyne 28 with tri-n-butylaldehyde in the presence of azobisisobutyronitrile.

1-Alkyl, 1-alkenyl, and 1-alkynylaryl-3-amino-1,3-propandiol of the present invention can be used as medicines for the treatment of memory disorders, particularly disorders associated with reduced cholinergic activity, which for example occurs in Alzheimer's disease. Activity to the weakening of memory disorders compounds of the present invention was investigated with a test for the avoidance of darkness, carried out on mice in order to determine the reducing action of the considered compounds with scopolamine-induced memory disorders associated with reduced levels of acetogenin in the brain. In this test, there were used three groups of 15 mice CFW /males/, namely: control group "filler/filler" group "scopolamine/filler", and group "scopolamine/drug". 30 minutes before training, the control group "filler/filler" was subcutaneously injected normal saline and groups "scopolamine/filler" and "scopolamin the five minutes before the start of training, the control group "filler/filler" and the group "scopolamine/filler" was administered distilled water, and the group "scopolamine/medicine" was administered the test compound in distilled water.

Device for training/testing contained chamber made of plexiglass, approximately 48 cm in length, 30 cm in height, which has a conical shape, pointed downwards /width of 26 cm at the top and up to 3 cm in the lower part/. Inside this chamber is divided by vertical partitions into two separate compartments, bright Department /illuminated mirror lamp 25 watt, suspended at a height of 30 cm from the floor/ in a dark office /covered/. In the lower part of the walls has a hole with a width of 2.5 cm and a height of 6 cm and a door-trap, which can drop to prevent the animal to pass in the next compartment. A device for inducing shock in small animals /Coulbourn Intrument/ was connected with two metal plates that can move along the length of the device, and in the dark compartment at a distance of 7.5 cm from the vertical partitions and 2 cm from the floor was placed a photocell. The behavior of the animals was monitored using 11/34 minicomputer with software-managed processes light Department directly under a fixed light source, and so the animals were turned down from the door leading into the dark compartment. The device is then closed and the system was brought into effect. If a mouse ran across the wall in a dark office and flags beam photocell within 180 s, the door fell, blocking the exit light Department, and mice were exposed to electric current intensity of 0.4 mA for three seconds. Then the animals immediately removed from the dark compartment and placed in their cells. If the animal failed to interrupt the beam of photocell within 180 with, these animals were eliminated from testing. For each mouse was recorded latency time in seconds.

After 24 hours, animals were again tested in the same device for testing, except that the mice did not enter the injections and they were not subjected to a shock. For each mouse was recorded latent time in seconds for the day of the test, after which animals were removed.

Specialists are well aware that one type of passive avoidance behavior when the test has a high degree of variability depending on the time of year, the conditions of detention and care). To account for this factor, for each in Addition, it was found that 5 to 7% in mice control.newgroup "scopolamine/filler" was insensitive to the dose of scopolamine 3 mg/kg, sc. Thus, WITH value defined as the second highest latent period in the control group to more accurately reflect 1/15 expected target responses in each test group. Experiments with a variety of standards, which were repeated under different environmental conditions, has allowed the development of the following criteria: for the considered test-values should be less than 120 seconds, the control group "filler/filler" should have at least 5/15 animals with latent periods in excess of WITH. For connection of the considered activity group "scopolamine/connection must have at least 3/15 hidden periods in excess of WITH.

The test results for the avoidance of darkness was expressed as number of animals per group in which scopolamine-induced memory loss is blocked, measured by the increase of the latent period. Activity recovery memory disorders characterized by compounds of the present compounds are presented in table 1.

Restoration of scopolamine-induced the Sam the compounds in the body with the specified disorder oral, parenterale or intravenous dose of from 0.01 to 100 mg/kg body per day. Particularly effective is the quantity of 25 mg/kg body per day. However, it is obvious that for each case can be set to a specific mode in accordance with the individual characteristics of the organism and the method of administration specified connection. Needless to say, the above doses are illustrative, and in no case do not limit the scope of the present invention.

1-alkyl, 1-alkenyl, and 1-alkynylaryl-2-amino-1,3-propandiol of the present invention can be also used as anti-inflammatory drugs due to their sposobnosti reduction of inflammatory processes in mammals. Testing anti-inflammatory activity of compounds was carried out using a test on TPA-induced ear oedema test and ear oedema induced by arachidonic acid, see J. V. Joung and other Journal Investigitive Dermatology 80, 48 (1983).

In the above analysis on TPA-induced ear oedema, TPA (12-o-tetradecanoylphorbol-13-acetate) was dissolved in a mixture of propylene glycol and ethanol (30:70) and the solution was applied to the right ear of the mice group consisting of 6 mice (females) Swiss Webster that 1 week before using them were placed the m 20 MK so, to the inner and outer surfaces of the ear had a total of 10 μg TPA. The test compound was dissolved in the filler and put it on the right ear (internal and external surfaces) in a volume of 20 μl, so that the ear as a whole passes 10 µg connection. After about 5 hours the animals were omertvlenie and from each ear were removed liner dia. 4 mm and weighed. Then determined the difference between the weight of the right and left ear of each animal. Anti-inflammatory activity of the test compounds were expressed as mean change in weight percentage of the ear gel treated animals compared with the average change in weight bearing control animals. The results of determining the anti-inflammatory activity of typical compounds of the present invention are presented in table 2.

In the analysis on ear oedema induced by arachidonic acid, the test compound was dissolved in a mixture of propylene glycol and ethanol (30:70) and were applied to both ears of mice group consisting of 6 female mice of Swiss Webster that 1 week prior to their use were kept together in a cage under standard conditions with food and water upon request, the processing of data was performed with a volume of 20 μl to nakagoe ear (everyone ear was treated with the same amount of filler (20 µl). After 30 minutes on the right ear of each group was applied arachidonic acid number of 4 mg/ear. And on the left ear of each mouse of each group was applied to the filler in the amount of 20 μl/ear. Again an hour later, the animals were killed and from each ear were removed liner with a diameter of 4 mm and weighed. For each animal was determined by the difference between the weights of the inserts right and left ear. Anti-inflammatory activity was defined as the average percentage change in weight of the ear gel treated animals as compared to the average percentage change in weight of the ear pad of the control group. Anti-inflammatory activity characteristics of the compounds of the present invention according to the analysis results presented in table 3.

Attenuation of the inflammatory process is achieved with the introduction of 1-alkylen, 1 alkenyl, and 1-alkynylaryl-2-amino-1,3-propandiol externally, for example by ophthalmic introduction as of the effective dose for external application from 0.001 to 100 mg/kg body per day. Especially effective amount is a dose of about 25 mg/kg of body weight per day. However, it is obvious that for each individual specialist can be installed in a specific implementation scheme depending no way limit the scope of the present invention.

1-alkyl, 1-alkenyl, or 1-quinil-2-aminopropanol of the present invention can be used as inhibitors of the growth of the tumor or malignant cells due to their ability to decrease cell proliferation, as can be shown by analysis of the protein kinase C (see U. Kikkawa and other Biochemical and Biophysical Research Comminications 135, 636 (1986) and R. M. Bell, and other "Methods in Enxylalagy, Hormone Achon", Part J, R. M. Conn. Ed. Academic Press, Inc. New York, NY 1986, page 353).

The extract of protein kinase C were obtained from the brain of Wistar rats (males) weighing 180 to 200 g, and was purified by the method of U. Kikkawa, etc. 636 ibid. The purified extract was stored at -80oC and aliquots were used in the analysis for protein kinase C, which was performed in accordance with modifikaciyami R. M. Bell and other al ibid 354.

For analysis used duplicate aliquots of duplicate samples. Each analysis involved the basal or nonactivated protein kinase C, phosphatidylserine/diacylglycerol-activated protein kinase C, and the test samples. To each tube containing the sample of non-activated protein kinase, chilled with ice, added extract protein kinases (1 5 g protein; 10 μl), 8 μl of a solution of N-2-hydroxyethylpiperazine-N'-2-ethylsulfanyl acids is 1 (12 mg, 8 μl), and calcium chloride (11 mm, 8 mm). To each test tube with the sample activated protein kinase, cooled with ice, was added phosphatidylserine/diacylglycerol (4 mg, 8 µl). Then the test tubes with samples cooled with ice, was added the test compound (10-410-12M 4 ál dimethyl sulfoxide). After this volume of all subjects tubes brought up to 72 μl of distilled water (18 μl for activated samples; 26 ál for unactivated samples without 8 mm phosphatidylserine/diacylglycerol). Subjects tubes were heated to 25oC and to each tube was added 8 μl of a mixture of adenosine 5-triphosphate (100 μm) and32P-ATP (1-2x105counts per minute) to obtain a final volume of 80 ál to each tube. After 2 minutes the reaction was completed with the inclusion of phosphorus in the histone type 111 by applying the reaction mixture to phosphocellulose paper. Spots printed on paper, cut out and the radioactivity of each spot (the number of counts per minute) was determined in a scintillation counter. Activity to inhibition of protein kinase C, i.e., the percentage of inhibition introduction32phosphorus from32P-ATP into histone type 111, was calculated as follows:

Activity and to test connection causing 50% inhibition of the absorption of phosphorus (IC50), are presented in table 4.

Inhibition of protein kinases is achieved with the introduction of the body requiring such treatment, 1-alkyl, 1-alkenyl, and 1-alkynylaryl-2-amino-1,3-propanediols of the present invention or related compounds orally, parenterally, intravenously or topically effective amount of from 0.001 or 0.01 to 100 mg/kg body per day. Especially effective amount is a dose of 25 mg/kg body per day. However, it should be noted that for each organism can be set to a specific receiving mode depending on the state of the individual and the method of administration of the medicinal product. Therefore, it is obvious that the above doses are illustrative, and in no case should not limit the scope of the present invention.

1-alkyl, 1-alkenyl, and 1-alkynylaryl-2-amino-1,3-propandiol of the present invention can also be used as antifungal and antibacterial agents blagodarya ability to inhibition of bacterial and fungal growth in mammals. Antibacterial and antifungal activity was illustrated using standard analysis Antibac aerobic bacteria was performed using the test using dilutions in agar Mueller-Hinton. Cups were inoculable using multipoint inoculator, which was introduced 5 x 104CFU/spot stationary, sugarsweetened cultures examined strains. The minimum inhibitory concentration MIC took the lowest concentration at which there is visible growth after 24 hours at 37oC.

Anaerobic analysis, i.e. the analysis on sensitivity to obligate gram-positive and gram-negative anaerobes, was performed using dilutions in agar Wilkins Chalgren. As inoculum used night cultures of the respective strains tested, diluted 1:10 in fresh thioglycollate environment. After the Cup was inoculable for 48 hours at 37oC anemostat, determined the MIC of antibiotics.

Antibacterial activity of typical compounds of the present invention defined in the above analysis, presented in tables 5 and 6.

Analysis of antifungal activity was performed using a technique micrometrology (u-shaped tablet 96 wells) at which the test compound (10 mg) was dissolved in an appropriate solvent (10 ml of distilled water or 1 ml of the organization. solvent + 9 ml distil. in/strain) 50 ál of neopath-dextrose broth (12-channel pipette). In addition, 1 row/strain were covered with 50 µl of a mixture of yeast nitrogen base per well for yeast and moulds. Then to each well of the first row was added 50 μl of a solution of the compounds were mixed and diluted with another 50 μl, respectively, in the ratio of 1:2. Then all wells were inoculable with 150 μl of titrated suspension of organisms yeast; 1 x 103organism/ml suspension; dermatomitsety and fungi; 1.6 x 105organism/ml suspension; total volume was 200 μl per well.

Have also used a control sample: increase (insulinopenia, without the introduction of drugs), the solvent (inoculated, without the introduction of drugs containing solvent instead of medicines in the respective rows), and negative control sample (not inoculated, without the introduction of drugs).

Incubation was performed for 5 days at 30oWith, and then carried out a photometric evaluation. The obtained measurements were examined visually, microscopically and microscopically and, if necessary, carried out the proper correction.

Criteria for the evaluation of antifungal activity

A. Photometric measurement matrix m is crocop, INCR. 64 x).

Antifungal activity of typical compounds of the present invention defined in the result of analysis by the method of micrometrology presented in table 7.

Inhibition of growth of bacteria and fungi can be achieved by the introduction of 1-alkyl, 1-alkenyl, and 1-alkynylaryl-2-amino-1,3 - propandiol or related compounds of the present invention in the body, requiring appropriate treatment, orally, parenterally, intravenously or topically, for example, by ophthalmic introduction, in the amount of from 0.01 to 100 mg/kg body per day. Especially effective dose is 25 mg/kg body per day. However, it should be noted that for each individual organism can be set to a specific mode of use of the medicinal product, depending on the condition of the body and way of doing the above connection. Therefore, it is obvious that these doses are illustrative, and in no case do not limit the scope of the present invention.

The compounds of the present invention are:

A. Erythro-2-amino-1-(5-decyl-2-furyl)-1,3-dihydroxypropane,

b. Erythro-2-amino-1-(5-decyl-3-isothiazole)-1,3 - dihydroxypropane,

C. Threo-2-amino-1-[5-decyl-3-(2-ocsober the REO-2-amino-1-[6-decyl-2-(4-methoxypyridine)] -1,3 - dihydroxypropane,

f. Erythro-2-amino-1-[6-decyl-2-(5-chloropyridinyl)] -1,3 - dihydroxypropane,

g. Tres-2-amino-1-[6-decyl-2-(4-triftoruranmetilidina)-1,3 - dihydroxypropane,

h. Erythro-3-amino-1-[6-(5-phenylmethyl-2-pyridinyl)] -1,3 - dihydroxypropane,

i. Erythro-2-amino-1-(2-decyl-4-thiazolyl)-1,3-hydroxypropan,

j. Erythro-2-amino-1-(2-decyl-4-oxazolyl)-1,3 - dihydroxypropane,

k. Erythro-3-methylamino-1-(5-decyl-2-thienyl)-1,3 - dihydroxypropane,

l. Erythro-2-dimethylamino-(3-decyl)phenyl-1,3 - dihydroxypropane,

m. Erythro-2-(1,1-dimethylmethoxy)carbylamine-1-(2-dodecenyl - 6-pyridinyl)-1,3-dihydroxypropane,

n. Erythro-2-amino-1-(3-(1-decenyl)phenyl)-1,3 - dihydroxypropane,

C. Ethyl Erythro-2-methoxycarbonylamino-3-(2-dodecyl-6 - pyridinyl)-3-hydroxypropionate,

R. Erythro-2-amino-1-(3-(1-decenyl)phenyl)-1,3 - dihydroxypropane,

q. Erythro-2-amino-1-(3-(1-undecenyl)phenyl)-1,3 - dihydroxypropane,

r. Erythro-2-amino-1-(4-(1-nonyl)-2-thienyl)-1,3 - dihydroxypropane,

s. Erythro-2-amino-1-(4-(1-dodecenyl)-2-thienyl)-1,3 - dihydroxypropane,

t. Erythro-2-amino-1-(4-(1-decyl)-2-thienyl)-1,3 - dihydroxypropane,

u. Erythro-2-amino-1-(5-nonyl-2-thienyl)-1,3-dihydroxypropane,

v. Erythro-2-amino-1-(3-dodecyl-5-isoxazolyl)-1,3 - dihydroxypropane,

w. Erythro-2-amino-1-(3-decyl-5-and the y. Erythro-2-amino-1-(3-phenyl-1-hexenyl)phenyl)-1,3 - dihydroxypropane, and

z. Erythro-2-amino-1-(5-(6-phenylhexa)-2-thienyl)-1,3 - dihydroxypropane.

Effective amounts of the present invention can be introduced into the body by external application in the form of sterile solutions, suspensions, ointments, creams or suspensions, 1-alkyl, 1-alkenyl, and 1-alkynylaryl-2-amino-1,3-propandiol of the present invention, which are themselves effective, can be introduced in the form of their pharmaceutically acceptable acidic or basic additive salts for purposes of stability, convenience of crystallization, increased solubility, etc.

Preferred pharmaceutically acceptable acid additive salts of the compounds of the present invention are salts of mineral acids such as hydrochloric acid, sulfuric acid, etc., salts of monobasic carboxylic acids such as acetic acid, propionic acid, etc., salts of dibasic carboxylic acids such as maleic, fumaric and other acids, and salts trekhosnovnykh carboxylic acids, for example, carboxyterminal acid, citric acid, etc. are Preferred pharmaceutically acceptable basic additive salts of the compounds nastoyashimi, calcium or magnesium; or complex salts such as ammonium salts or substituted ammonium, for example, salts of mono-, di-, or trialkylamine or salts of mono-, di-, or trihydroxystilbene.

For local use of the active compounds of the present invention can be introduced into solutions, suspensions, creams, gels, ointments or sprays. These preparations may contain at least 0.1% of active compound, however, the number of the specified active compounds can vary from 0.05 to about 20% of the mass. The number of active compound in these compositions should be such that it matches the desired dose. Preferred preparations for external use containing from 0.1 to 10% of active compound.

Compositions for topical application can include the following components: water, fixed oils, polyethylene glycols, glycerine, oil, stearic acid, beeswax, other synthetic solvents and mixtures thereof; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as tocopherol acetate; hepatoblastoma agents, such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates; among is whether talc. Drugs for external use mouthbut be contained in tubes, bottles or cans made of metal, glass or plastic.

Active compounds of the present invention can also be administered orally, for example, in combination with an inert diluent or edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For oral administration, the above compounds may be used in combination with inert fillers in the form of standard dosage forms, such as tablets, lozenges, capsules, elixirs, suspensions, syrups, wafers, chewing gum, etc., These preparations may contain at least 0.5% of active compound, but the number can vary depending on its specific type in the range from about 4% to about 75% by weight of a single dose. A number of compounds of the present invention in such compositions should correspond to the desired dose. Preferred compositions and preparations of the present invention are such drugs, in which a single dose for oral administration contains 1.0 to 300 mg of active compound.

Tablets, pills, lozenges, capsules, etc. Latin; inert filler, such as starch or lactose; disintegrity agent, such as alginic acid, primogel, corn starch, etc., a lubricant such as magnesium stearate or sterate; videostwo promoting sliding,such as colloidal silicon dioxide; and a sweetening agent, such as sucrose or saccharin or a flavoring substance, such as peppermint, methyl salicylate or orange flavoring. If disposable dosage form is a capsule, in addition to the above substances, it may also contain a liquid carrier such as fatty oil. Other dosage forms may also contain other substances that are designed to modify the appearance of the dosage form, such as coating. Tablets or pills may be coated with sugar, shellac or other intersolubility coating. A syrup may contain, in addition to the active compounds sweetening agent, for example, sucrose, and certain preservatives, dyes and fragrances. All substances used in the manufacture of various compositions, described above, should be pharmaceutically pure and non-toxic.

For parenteral administration, actively to contain, at least 0.1% of active compound, however, can vary from about 0.5 to about 50 wt%. The number of active compounds in such compositions should correspond to the required dose. Preferred compositions and preparations of the present invention, intended for parenteral administration, the compositions are, the single dosage form which contains from 0.5 to 100 mg of active compound.

Solutions and suspensions for oral administration may also contain the following components: a sterile diluent such as water for injection, saline solution, fixed oil, polyethylene glycol, piperin, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfate; hepatoblastoma agents, such as ethylenediaminetetraacetic acid; buffers such as acetates; citrates or phosphates and toning agents, such as sodium chloride or dextrose. The preparation for parenteral administration may be made in the form of capsules and can be contained in disposable syringes or containers for multiple doses, the, however, in no case do not restrict its nature and scope.

Example 1

6-(1-dodecenyl)-2-pyridinecarboxamide

To a solution of 6-bromo-2-pyridinecarboxamide (3.0 g) in tetrahydrofuran (10 ml) was added sequentially chloride bis(triphenylphosphine)palladium (II) (0,178 g), copper iodide (I) (0,024 g), 1-dodecen (of 3.25 ml), and triethylamine (2,12 ml). The solution is stirred overnight at 40oC. Then the reaction mixture was cooled to room temperature, was again loaded chloride bis(triphenylphosphine)palladium (II) (0,024 g), copper iodide (I) (0,024 g), and triethylamine (2,12 ml) and 1-dodecanol (of 3.25 ml), and tetrahydrofuran (5.0 ml), and heated at 40oC for 5 hours. Media reaction mixture is again cooled and again loaded, as described above, and heated at 40oC for 24 hours. The cooled mixture was concentrated, diluted with ethyl acetate (100 ml), washed with water and saturated sodium chloride solution, dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was dissolved in ethyl acetate (100 ml) and filtered. The filtrate was combined with the product from a similar reaction party 1,43 g carboxaldehyde and appropriate proportional amounts of catalyst, 1-Modesto eluents 1.5% mixture of ethyl acetate and hexane, and then 1% of a mixture of acetate and hexane. The appropriate fractions were collected and concentrated, resulting in a received 2.24 g (29%) of product as an oily substance.

Analysis: C18H25NO;

Calculated: 79,66% C, 9.28 are% H, N 5,16%

Found: 79,54% C, 9,29% H, N 4.98% OF

Example 2

Erythro-N-{ 1-[6-(1-decenyl)-2-pyridinyl]-1,3-dihydroxy-2 - propanyl}ndimethylacetamide

Ethyl Erythro-2-acetamido-3-[6-(1-decenyl)-2-pyridinyl]-3 - hydroxypropionate (5,71 g) in dry tetrahydrofuran (75 ml) was slowly added 4 2.0 M of lithium borohydride and tetrahydrofuran (7,6 ml) at 0oC in nitrogen atmosphere, and the mixture is stirred over night at room temperature. The reaction mixture was cooled and slowly added a mixture of methanol and water (1:1), (50 ml) followed by the addition of explicilty (0.5 ml) up until the pH is about 6.5. Then the reaction mixture was concentrated, and the residue was doing azeotrope with methanol (4 x 40 ml). The residue is suspended in 7.5% sodium bicarbonate solution (15 ml, pH 8.5), was extracted with 3:1 - trichlormethane:isopropanol and concentrated. The appropriate fractions were collected and concentrated. The residue was purified using flash chromatography on silica gel, elwira a mixture of ethyl acetate and methanol (49:1). Corresponding to the Analysis for C20H30N2O3< / BR>
Calculated: C 69,33, H 8,73, N 8.09

Found: C 69,44, H 8,84, N 8,07

Example 3

Erythro-N-{1-[6-(1-decenyl)-2-pyridinyl]-1,3-deacetylase-2 - propanyl}ndimethylacetamide

N-{ 1-[6-(1-Decenyl)-2-pyridinyl] -1,3-dihydroxy-2-propanyl} ndimethylacetamide (4.35 g), acetic acid (7,45 ml), triethylamine (16 ml) and 4-dimethylaminopyridine (0.24 g) in dry tetrahydrofuran (80 ml) stirred at room temperature for 3 days. The reaction mixture is evaporated and the residue was heated with methanol for 20 minutes, then evaporated, and the residue was doing azeotrope with toluene. The residue was dissolved in trichloromethane, then added 7.5% sodium bicarbonate solution up until the pH is not equal to 8.5. The mixture was extracted with trichloromethane, was dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was combined with the residue(1.0 g) from another reaction (0,829 g ndimethylacetamide) and was purified using flash chromatography on silica gel, elwira with a mixture of hexane and ethyl acetate (1:1). The appropriate fractions were collected, concentrated and received in the result of 1.61 g (25%) of the product.

Analysis for C24H34N2O5: (%)

Calculated: C 66,95, H of 7.96, N 6,51

Found: 66,65, N 8,04, N 6,36

Example 1,3-dihydroxy-2-propanyl} ndimethylacetamide (4.35 g), acetic acid (7,45 ml), triethylamine (16 ml) and 4-dimethylaminopyridine (0.24 g) in anhydrous tetrahydrofuran (80 ml) stirred at room temperature for 3 days. The reaction mixture is evaporated and the residue was heated with methanol for 20 min, then evaporated and did azeotrope using toluene. The residue was dissolved in trichloromethane, and to bring the pH to 8.5 was added 7.5% sodium bicarbonate solution. The mixture was extracted with trichloromethane, was dried with anhydrous magnesium sulfate, filtered and concentrated. The residue was combined with 10 g of the residue from other reactions (0,929 g ndimethylacetamide) and was purified using flash chromatography on silica gel, elwira with a mixture of hexane and ethyl acetate (1:1), resulting in a received 1,02 g (15,9%) of product, so pl. 59 61oC.

Analysis for C24H34N2O5: (%)

Calculated: C 66,95, H of 7.96, N 6,51

Found: C 66,21, H 7,83, N Of 5.92.

Example 5

Ethyl Erythro-2-acetamido-3-[6-(1-decenyl)-2-pyridinyl]-3 - hydroxypropionate

Erythro: threo-mixture (2:1) ethyl 2-acetamido-3-(6-bromo-2 - pyridinyl)-3-hydroxypropionate (10.0 g), 1-decina (5,01 g), bis(triphenylphosphine)pallidiflora (0,42 g) and copper iodide (0.06 g) in triethylamine (50 ml) was heated for 2.5 h at 50 60oC in the atmosphere is added to water, and were extracted with ethyl acetate. The organic extract was purified using flash chromatography on silica gel, elwira with a mixture of hexane and ethyl acetate (1:1), and appropriate fractions were collected. The obtained fractions evaporated. After recrystallization from acetic acid ethyl ester was obtained 7.8 g (66%) of product, so pl. 97 99oC.

Analysis of C22H32N2O4: (%)

Calculated: C 68,01, 8,30 H, N 7,21

Found: C 68,23, H of 8.28, N 7,22

Example 6

Ethyl, threo-2-acetamido-3-[6-(1-decenyl-2-pyridinyl]-3 - hydroxypropionate

A mixture of ethyl 2-acetamido-3-(6-bromo-2-pyridinyl)-3 - hydroxypropionate (17.3 g, 97% Erythro), 1-decina (8,67 g) chloride bis(triphenylphosphine)palladium (0.73 g), copper iodide (0.10 g), and triethylamine (13,2 g) in tetrahydrofuran (90 ml)was heated overnight at 50 55oC in nitrogen atmosphere. The reaction mixture was evaporated, added water and the resulting mixture was extracted with ethyl acetate and concentrated. The residue was purified using flash chromatography on silica gel, elwira with a mixture of hexane and ethyl acetate (1:1). The appropriate fractions were collected and evaporated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1:2) was received of 14.7 g of a mixture of Erythro-threo (19:1) compounds, and from the mother solution of 4.66 g of a mixture of Erythro-threo (8:3) with what MESU of hexane and ethyl acetate (1:1), received 0.39 g (3,4%) of product, so pl. 97 to 99.5oC.

Analysis for C22H32N2O4: (%)

Calculated: C 68,01, 8,30 H, N 7,21

Found: C 67,89, H compared to 8.26, N 7,10

Example 7

Erythro-N-{ 4-[6-(1-Decenyl)-2-pyridinyl] -2,2-dimethyl-1,3 - dioxane-5-yl} ndimethylacetamide

N-{ 1-[6-(1-Decenyl)-2-pyridinyl] -1,3-dihydroxy-2-propanyl} ndimethylacetamide (6,1 g of a mixture of Erythro: threo (3: 1), p-toluensulfonate acid (3.7 g), and 2,2-dimethoxypropane (43 ml) in dichloromethane (115 ml) was stirred overnight at room temperature in a nitrogen atmosphere. Then the reaction mixture was extracted with 0.5 M sodium bicarbonate solution and water, dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The residue was chromatographically on silica gel, buyrates of hexane and ethyl acetate (2:1), and was obtained 2.4 g (35%) of product in the form of butter.

Analysis: C23H34N2O3(%):

Calculated: C 71,47, H 8,87, N 7,25

Found: C 71,14, H 9,12, N 7,13.

Example 8

Threo-N-{4-[6-(1-Decenyl)-2-pyridinyl]-2,2-dimethyl-1,3 - dioxane-5-yl}ndimethylacetamide

N-{ 1-[6-(1-Decenyl)-2-pyridinyl] -1,3-dihydroxy-2-propanyl} ndimethylacetamide (6,1 g, a mixture of Erythro-threo 3:1), p-toluensulfonate acid (3.7 g) and 2,2-dimethoxypropane (43 ml) in dichloromethane (115 ml) was stirred for n is that of sodium and water, was dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was chromatographically twice on silica gel, elwira with a mixture of hexane and ethyl acetate in a gradient (2: 1 1:1), and resulted 0,76 g (11%) of product as an oily substance.

Analysis of C23H34N2O3< / BR>
Calculated: C 71,47, H 8,87, N 7,25

Found: C 71,15, H 8,91, N 7,06

Example 9

Ethyl Erythro-2-acetamido-3-[6-(1-dodecenyl)-2-pyridinyl]-3 - hydroxypropionate

A solution of 6-(1-dodecenyl)-2-pyridinecarboxamide (5,51 g), complex monoethylene ether acetamidomalonate acid(of 3.78 g), and triethylamine (2.8 ml) in dry tetrahydrofuran (30 ml) stirred at room temperature and under nitrogen atmosphere over night. Then the reaction mixture is evaporated and the residue was purified on a column of silica gel, elwira with a mixture of hexane and ethyl acetate (1: 1), resulting in a received 7,46 g (89,6%) of the product (10:1 Erythro-threo-mix). The product was combined from 7.40 g of another reactionary party in the same scale, and the resulting combined product was recrystallized from a mixture of ethyl acetate and hexane (2:1), resulting in a received 9,72 g (57,7%) of analytically pure product, so pl. 86 87,5oC.

Analysis for C24H36N2is IDO-3-[6-(1-hexenyl)-2-pyridinyl] -3 - hydroxypropionate

Erythro-threo (11:1) mixture of ethyl 2-acetamido-3-(6-bromo-2 - pyridinyl)-3-hydroxypropionate (24,9 g), 1-hexyne (7,39 g), triethylamine (19,0 g) chloride bis(triphenylphosphine)palladium (1,05 g) and copper iodide (0.14 g) in anhydrous tetrahydrofuran (1000 ml) was heated for 6 hours at 55oC in nitrogen atmosphere. Then at room temperature was added 6.2 g of 1-hexyne, 7.6 g of triethylamine, of 0.53 g of chloride bis(triphenylphosphine)palladium, and 0.07 g idoido copper, and the resulting reaction mixture was heated for another 5.5 hours. After which the mixture is evaporated, added water and ekstragirovaniem. The extract was chromatographically on silica gel, elwira with a mixture of hexane and ethyl acetate (1:1). The appropriate fractions were collected and evaporated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1:1) was obtained 3.8 g (15%) of the product, so pl. 87 88oC.

Analysis for C18H24N2O4: (%)

Calculated: C 65,04, H 7,28, N 8,43

Found: C 65,19, H 7,31, N OF 8.37

Example 11

Erythro-N-{1,3-deacetylase-1-[6-(1-hexenyl)-2-pyridinyl]- propenyl}ndimethylacetamide

To acelerado-2-acetamido-3-[6-(1-hexenyl)-2-pyridinyl] -3 - hydroxypropionate (16.0 g) in anhydrous tetrahydrofuran (140 ml) was added 2.0 M of borohydride lithium: tetrahydrofuran (24 ml) at 0oC, re is espesially during the night. Then the mixture was cooled and slowly added a mixture of water and ethanol (1:1) followed by the addition of acetic acid (2.8 ml) in order to bring the pH to 6.8. The resulting mixture was stirred for 1 hour and evaporated. The residue is repeatedly subjected azeotrope methanol. Then to the residue was added 7.5% sodium bicarbonate solution to obtain a pH of 8.5, and the mixture was extracted with a mixture of trichloromethane and isopropanol (3:1), and concentrated. The residue was subjected to flash chromatography, elwira 1% methanol-ethyl acetate, and was received with 13.2 g (94%) of Erythro-N-{1-[6-(1-hexyl)-2-pyridinyl]-1,3 - dihydroxy-2-propanyl}ndimethylacetamide.

Erythro-N-{ 1-[6-(1-hexenyl)-2-pyridinyl] -1,3-dihydroxy-2 - propanyl} ndimethylacetamide (10.3 g), acetic anhydride (21.8 g), triethylamine (32,4 g) and 4-dimethylaminopyridine (0,44 g) in tetrahydrofuran (150 ml) stirred at room temperature overnight. The reaction mixture was evaporated, to the residue was added methanol, and the resulting solution was heated for 15 minutes at 50oC. the Mixture is evaporated. The residue was dissolved in chloroform and added with 7.5% sodium bicarbonate solution to obtain a pH of 8. Then the mixture was extracted with chloroform. The extract was dried with anhydrous magnesium sulfate was filtered, and the filtrate koncentrira of 7.3 g of 55% of the product, so pl. 97 99oC.

Analysis for C20H26N2O5(%):

Calculated: C 64,16, H 7,00, N OF 7.48

Found: C 64,17, H 7,00, N 7,44

Example 12

Erythro-N-{1-[6-(1-Hexenyl)-2-pyridinyl]-1,3-dihydroxy-2 - propanyl}ndimethylacetamide

Erythro-N-{ 1,3-deacetylase-1-[6-(1-hexenyl)-2-pyridinyl] -2 - propanyl} ndimethylacetamide (6.7 g) and potassium carbonate (3.3 g) in methanol (100 ml) stirred for 40 minutes. The precipitate was collected, and the filtrate evaporated. To bring the pH to 8.5 was added 7.5% sodium bicarbonate solution, and the resulting mixture was extracted with a mixture of trichloromethane and 2-propanol (3:1), dried with anhydrous magnesium sulfate, and the filtrate evaporated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1:1) was obtained 4.6 g (88%) of product,so pl. 75 77oC.

Analysis for C16H22N2O5(%):

Calculated: C 66,19, H of 7.64, N 9,65

Found: C 65,99, H of 7.55, N 9,65

Example 13

Ethyl Erythro-2-acetamido-3-hydroxy-3-[6-(1-octenyl)-2 - pyridinyl]propionate

A mixture of (Erythro: threo (11:1) ethyl 2-acetamido-3-(6-bromo-2 - pyrimidyl)-3-hydroxypropionate (24,9 g), 1-octene (9,9 g), triethylamine (19,0 g) chloride bis(triphenylphosphine)palladium (1,05 g), and copper iodide (0.14 g) in anhydrous tetrahydrofuran (100 ml) was heated for 6 hours at 55oC the IP triphenylphosphine palladium, and 0.07 g of copper iodide, and the reaction mixture was heated for another 4 hours. After which the mixture is evaporated, added water, and the mixture was extracted with ethyl acetate. The solution was subjected to flash chromatography on silica gel, elwira hexane and ethyl acetate (1: 1). Fractions enriched Erythro-isomer, evaporated, and the residue was recrystallized from a mixture of isopropanol and water (1:1), which was obtained 3.2 g (12%) of product, so pl. 81 83oC.

Analysis for C20H28N2O4< / BR>
Calculated: C 66,64, H 7,83, N TO 7.77

Found: C 66,62, H to 7.77, N 7,75

Example 14

Erythro-N-{1,3-Dihydro-1-[6-(1-octenyl)-2-pyridinyl]-2 - propanyl}ndimethylacetamide

To ethyl Erythro-2-acetamido-3-hydroxy-3-[6-(1-octenyl)-2 - pyridinyl] propionate (9,02 g) in anhydrous tetrahydrofuran (80 ml) was added slowly 2.0 M of borohydride lithium/tetrahydrofuran (12.5 ml) at 0oC in nitrogen atmosphere. The mixture is stirred over night at room temperature, then cooled and slowly added methanol and water (1:1) followed by the addition of glacial acetic acid 1.5 ml in a mixture of methanol water (1:1, 15 ml) to obtain a pH of 6.8. The resulting solution was stirred at room temperature for 1.5 hours, and the residue was subjected to azeotropy with methanol (4 x 40 ml). The remainder of suspend and a mixture of trichloromethane and 2-propanol (3: 1), and concentrated. The residue was subjected to flash chromatography on silica gel, elwira a mixture of ethyl acetate and 0.5% methanol. The appropriate fractions were collected and evaporated. The residue was recrystallized 3 times from ethyl acetate and was received as a result of 1.24 g (15,6%) of product, so pl. 81 83oC.

Analysis of C18H26N2O3(%):

Calculated: C 67,90, H 8,23, N 8,80

Found: C 68,03, H of 7.97, N 8,70

Example 15

Ethyl Erythro-2-acetamido-3-[6-(1-hexadecynyl)-2-pyridinyl] - 3-hydroxypropionate

A solution of 6-(1-hexadecynyl)-2-pyridinecarboxamide a (17.4 g), monoethylene of ester acetamidomalonate acid (10.6 g), and triethylamine (5.4 ml) in anhydrous tetrahydrofuran (85 ml) was stirred for 3 hours at room temperature in a nitrogen atmosphere. Then the reaction mixture is evaporated, and the residue was dissolved in ethyl acetate. The solution was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was purified flash chromatography on silica gel, elwira with a mixture of hexane and ethyl acetate in a gradient (2:1 1:1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethanol and then from 85% ethanol, and was obtained 12.8 g (50,9%) products is
Found: C 70,86, N 9,18, N OF 5.82

Example 16

Erythro-N-{ 1-[6-(1-dodecenyl)-2-pyridinyl] -1,3-dihydroxy-2 - propanyl} ndimethylacetamide

To a solution of ethyl Erythro-2-acetamido-3-[6-(1-dodecyl)- pyridinyl]-3-hydroxypropionate (20,3 g) in anhydrous tetrahydrofuran (250 ml) was added a 2.0 M lithium borohydride/tetrahydrofuran (30 ml) at 0oC, in nitrogen atmosphere. The reaction mixture is stirred over night at room temperature. The mixture was cooled and slowly added methanol and water(1:1) followed by the addition of glacial acetic acid (3.5 ml) in a mixture of methanol and water (1:1, 50 ml) to obtain a pH of 6.5. The solution is stirred for 2 hours at room temperature, then the solvents evaporated, and the residue was subjected to azeotropy with methanol (5 x 100 ml). Then the residue is suspended in 7.5% sodium bicarbonate solution (65 ml, pH 8.5), was extracted with a 3:1 mixture of chloroform and 2-propanol, and then concentrated. The residue was subjected to flash chromatography on silica gel, elwira mixture of 0.5% methanol and ethyl acetate. The appropriate fractions were collected and evaporated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1: 1), was obtained 15.5 g (85,0%) of product, so pl. 86 - 88oC.

Analysis of C22H34N2O3(%):

Calculated: C is oxypropane

Ethyl Erythro-2-acetamido-3-[6-(1-decenyl)-3 - hydroxypropionate] (2.7 g) in ethanol (65 ml) was reconstructed using 5% palladium carbon (0.7 g) in hydrogenator Parra at hydrogen pressure of 40 pounds per square inch (275,76 kPa). After 2.5 hours, the catalyst was collected, the filtrate evaporated, and the residue was recrystallized from ethyl acetate, resulting in a received 2,11 g (77,6%) of product, so pl. 67 68,5oC.

Analysis of C22H36N2O4: (%)

Calculated: C 67,32, H 9,24, N 7,14

Found: C 66,96, H 9,13, N 7,08

Example 18

Erythro-N-{1-[6-Decyl-2-pyridinyl)-1,3-dihydroxy-2 - propanyl}ndimethylacetamide

Erythro-N-{ 1-[(6-decenyl)-2-pyridinyl]-1,3-dihydroxy-2 - propanyl}ndimethylacetamide (4.0 g) in ethanol (100 ml) was reconstructed using 5% palladium carbon (0.1 g) in hydrogenator Parra at hydrogen pressure of 40 pounds per square inch (275,76 kPa). After 2 hours the catalyst was collected, the solvent evaporated, and the residue was precrystallization of ethyl acetate, resulting in received of 3.69 g (91%) of product, so pl. 94 96oC.

Analysis of C20H34N2O3(%):

Calculated: C 68,54, H 9,78, N 7,99

Found: C 68,36, H 9,72, N 7,94

Example 19

Threo-2-amino-1-(6-decyl-2-pyridinyl)-1,3-dihydroxypropane

Threo-N-{ 1-[6-(1-Decyl)-2-feast of the cell carbon (0.06 g) in hydrogenator Parra at hydrogen pressure of 40 pounds per square inch (275,76 kPa). After two hours, the catalyst was collected, and the solvent is evaporated, resulting in a received 0.95 g (94%) threo-N-[3-(6-decyl-2-pyridinyl)-1,3-deacetylase-2-propenyl] ndimethylacetamide.

The ndimethylacetamide (0.95 g), hydrazinehydrate (40 ml), and ethanol (20 ml) was heated in a flask under reflux in nitrogen atmosphere for 25 hours. The reaction mixture was cooled was added water (30 ml) and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, and the filtrate evaporated. The residue was chromatographically on silica gel, elwira in the gradient 980:20:2 970:30:2. The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate, washed polysystem solution of sodium chloride, dried, filtered and after evaporation of the filtrate was obtained 0.50 g (72%) of product, so pl. 76 78oC.

Analysis of C18H32N2O2(%):

Calculated: C 70,09, H 10,46, N 9.08

Found: C 70,02, H 10,63, N cent to 8.85

Example 20

Erythro-2-amino-1-(6-decyl-2-pyridinyl)-1,3-dihydroxypropane.

Erythro-N-[1-(6-decyl-2-pyridinyl)-1,3-dihydroiso-2 - propenyl] ndimethylacetamide (6.0 g), hydrazinehydrate (60 ml), and ethanol (15 ml) was heated in a vessel under reflux in PR what dilatatum. An ethyl acetate layers were washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was combined with the 1.44 guise of the other two experiments, and the combined product was chromatographically on silica gel, elwira mixture of trichloromethane, methanol and 2n ammonium hydroxide in the gradient 950:50:3 900:100:5. The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate (150 ml) and the solution was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, and the filtrate is evaporated, resulting in a received ceiling of 5.60 g (79%) of product, so pl. 52 55oC.

Analysis of C18H32N2O2(%):

Calculated: C 70,09, H 10,46, N REMAINING 9.08

Found: C 69,63, H 10,29, N 8,87

Example 21

Ethyl Erythro-2-acetamido-3-(6-dodecyl-2-pyridinyl)-3 - hydroxypropionate

Ethyl Erythro-2-acetamido-3-[6-(1-dodecenyl)-2-pyridinyl] -3 - hydroxypropionate (2.0 g) in ethanol (80 ml) containing 5% palladium carbon (0.06 g) was restored in hydrogenator Parra at hydrogen pressure of 40 pounds per square inch (275,76 kPa). After two hours the catalyst was filtered, the filtrate evaporated, the residue was recrystallized in ethyl acetate, and received 1.42 g (70,3%) of product, so pl. 71 73o N 6,69

Example 22

Erythro-N-[1-(6-dodecyl-2-pyridinyl)-1,3-dihydroxy - 2-propanyl]ndimethylacetamide

Erythro-N-{ 1-[6-(1-dodecenyl)-2-pyridinyl] -1,3-dihydroxy - 2-propanyl} ndimethylacetamide (6,05 g) in ethanol (120 ml) containing 5% palladium charcoal (0.15 g) was restored in hydrogenator Parra at hydrogen pressure of 30 pounds per square inch (206,82 kPa). After two hours the catalyst was filtered, the filtrate evaporated, and the residue was recrystallized from ethyl acetate, resulting in a received 5,90 g (96,4%) of product, so pl. 99 to 100.5oC.

Analysis of C22H38N2O3(%):

Calculated: C 69,80, H 10,12, N 7,40

Found: C 69,71, H 10,37, N 7,34

Example 23

Erythro-2-amino-1-(6-dodecyl-2-pyridinyl)-1,3-propandiol.

Erythro-N-[1-(6-dodecyl-2-pyridinyl)-1,3-dihydroxy-2 - propanyl]ndimethylacetamide (3.8 g), hydrazinehydrate (35 ml), and ethanol (20 ml) was heated in a vessel under reflux in the presence of nitrogen within 24 hours. The reaction mixture was cooled, added to water (50 ml) and the resulting mixture was extracted with chloroform (3 × 65 ml). The extracts were washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The residue was chromatographically on silica gel, elwira mixture of chloroform, methanol and orida sodium,and dried with anhydrous magnesium sulfate, was filtered, and the filtrate is evaporated, resulting in a received 2,10 g (62%) of product, so pl. 61 64oC.

Analysis of C20H36N2O2< / BR>
Calculated: C 71,38, H 10,78, N 8,32

Found: C 71,04, H 10,95, N 8,07

Example 24

Erythro-N-[1-(6-hexyl-2-pyridinyl)-1,3-dihydroxy-2 - propanyl]ndimethylacetamide

Erythro-N-{1-[6-(1-hexenyl)-2-pyridinyl]-1,3-dihydroxy-2 - propanyl}ndimethylacetamide (5,80 g) in ethanol (125 ml) was hydrogenosomal using 0.15 g of 5% palladium angle in the system Parra at a pressure of 40 pounds per square inch 275,76 kPa. After 2.5 hours, the catalyst was collected, the filtrate evaporated, and the residue was recrystallized from ethyl acetate, which was received with 5.2 g (88,6%) of product, so pl. 75 76,5oC.

Analysis of C16H26N2O3(%):

Calculated: C 68,28, H 8,90, N 9,52

Found: C 68,18, H 8,78, N 9,50

Example 25

N, O, O-Tribenzylamine-Erythro-2-amino-1-(6-decyl-2 - pyridinyl)-1,3-propandiol

Erythro-2-amino-1-(6-decyl-2-pyridinyl)-1,3-propandiol (1.50 g) N-benzyloxycarbonylglycine (4,00 g) and triethylamine (2,23 ml) in anhydrous tetrahydrofuran (60 ml) stirred at room temperature under nitrogen atmosphere for 9 days. Then was added N-benzyloxycarbonylglycine (4,00 g) and continued lane is washed with a saturated solution of sodium chloride, was dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was purified using flash chromatography on silica gel, elwira with a mixture of hexane and ethyl acetate (9:1). The appropriate fractions were collected and evaporated, resulting in received of 1.87 g (54%) of product.

Analysis of C42H50N2O8(%):

Calculated: C 70,96, H 7,09, N 3,94

Found: C 71,00, H 6,92, N OF 3.77

Example 26

Ethyl Erythro-2-acetamido-3-hydroxy-3-[3-(1-undecenyl)phenyl] propionate

To a solution of 3-bromobenzaldehyde (30,3 g) and 1-undecene (29.5 g) in triethylamine (120 ml) was added chloride bis triphenylphosphine palladium 11 (1.9 grams), and then copper iodide 1 (0.25 g). The mixture is stirred in the dark for 6 h at 55oC and under nitrogen atmosphere. After cooling to room temperature the reaction mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water and a saturated solution of sodium was dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated, which was received with 45.8 g of 3-(1-undecenyl)benzaldehyde in the form of an oily substance.

A solution of 3-(1-undecenyl)benzaldehyde (23,0 g), monoethylene of ester acetamidomalonate acid (15.1 g) and triethylamine (11.2 ml) in anhydrous then it is carbonated(7.6 g) of monoethylene of ester acetamidomalonate acid (5.6 ml) of triethylamine, and continued to stir for 72 hours. The reaction mixture is evaporated and the residue was purified on a column of silica gel, elwira with a mixture of hexane and ethyl acetate (2: 1), resulting in a received 13,0 g (41%) of product. The obtained product was dissolved in a warm mixture of water and ethanol 3:2. The precipitate was collected. The filtrate was concentrated, and the residue is recrystallized from cyclohexane, resulting in the received analytical sample, so pl. 69 - 71oC.

Analysis of C24H35NO4(%):

Calculated: C 71,79, H 8,79, N 3,49

Found: C 71,81, H 8,72, N 3,51

Example 27

Ethyl Erythro-2-acetamido-3-3-(1-dodecenyl)phenyl-3 - hydroxypropionate

To a solution of 3-bromobenzaldehyde (26.5 g) and 1-dodecyne (25,0 g) in triethylamine (105 ml) was added chloride bis(triphenylphosphine) palladium (II) (1.9 grams), and then copper iodide (I) (1.9 grams), and then copper iodide (I) (1.9 grams). The mixture is stirred in the dark at 55oC and under nitrogen atmosphere for 7 hours. After cooling to room temperature the reaction mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water and saturated sodium chloride solution, dried with anhydrous magnesium sulfate, filtered, and concentrated, resulting in received of 37.7 g of 3-(1-dodecenyl)benzaldehyde. The filtrate receive the second broadcast acetamidomalonate acid (5.1 g), triethylamine (3.8 ml) in anhydrous tetrahydrofuran, 35 ml stirred at room temperature and under nitrogen atmosphere for 48 hours. Then was added (2.6 g) of monoethylene ether acetamidomalonate acid (1.9 ml) of triethylamine, and the mixture is stirred for 72 hours. The mixture is evaporated and the residue was purified on a column of silica gel, elwira with a mixture of hexane and ethyl acetate (2:1, and was obtained 4.8 g (43%) of product. The product was dissolved in a warm mixture of ethanol and water (3:2), and then cooled. The precipitate was collected. The filtrate was concentrated, and the residue was recrystallized from a mixture of ethyl acetate and hexane (1:2), resulting in the received analytical sample, so pl. 80 82oC.

Analysis of C25H37NO4(%):

Calculated: C 72,26, H 8,97, N 3,37

Found: C 72,34, H, a total of 8.74, N 3,38

Example 28

CIS-Erythro-N-{ 1-[6-(1-dodecenyl)-2-pyridinyl] -1,3 - dihydroxy-2-propanyl}ndimethylacetamide

Erythro-N-{1-[6-(1-dodecenyl)-2-pyridinyl]-1,3-dihydroxy-2 - propanyl}ndimethylacetamide (2,05 g) in ethanol (55 ml), 5% palladium barium sulfate (0.02 g) and 0.04 g of quinoline were hydrogenosomal at atmospheric pressure until, until absorbed 1 EQ. hydrogen (approx. 123 ml). The catalyst was filtered, the filtrate evaporated and the residue (2.1 g) was combined with the residue (3.5 g) the acetate in a gradient of 1:2 to 1:4, and received 1,58 g (28%) of product, so pl. 96 98oC.

Analysis of C22H36N2O3(%):

Calculated: C 70,18, H for 9.64, N 7,44

Found: C 70,17, H 9,67, N 7,43

Example 29

5-(1-dodecenyl)-2-thiophenecarboxaldehyde

A solution of 1-dodecene (28,7 g), 5-bromo-2 - thiophenecarboxaldehyde (300 g) and triethylamine (47,7 g) in anhydrous tetrahydrofuran (75 ml) was degirolami and stirred at room temperature and under nitrogen atmosphere. Then to the mixture was added chloride bis(triphenylphosphine)palladium (II) 2 M followed by the addition of copper iodide (I) (1 M). The mixture was degirolami and was stirred for 3 hours at room temperature and under nitrogen atmosphere. The precipitate was collected and washed with ethyl acetate and the filtrate evaporated. The residue was distilled in a furnace (the furnace temperature 175 C/0.1 mm RT.CT.) and received 27,1 g (62%) of product as oil. Part of this product was purified using flash chromatography on silica gel, elwira mixture of hexane and dichloromethane (7:3) and was dried for 3 hours at 50oC in vacuum, resulting in the received analytical sample.

Analysis of C17H24OS (%):

Calculated: C 73,86, H 8,75

Found: C 73,86, H 8,72

Example 30

Ethyl Erythro-2-acetamido-3-[5-(1-dodecenyl)-2-thienyl]-3 - hydroxypropionate

s (21,7 g), and anhydrous tetrahydrofuran (150 ml) was degirolami and was cooled to 0oC. Then was added triethylamine (5% excess), the solution was degirolami, and the reaction mixture stirred for 2 days at room temperature and under nitrogen atmosphere. Then was added (21,7 g) of monoethylene of ester acetamidomalonate acid and 5% excess of triethylamine, and the reaction mixture stirred at room temperature for 5 days under nitrogen atmosphere. The mixture is evaporated and the residue was purified using flash chromatography on Krasnosel, elwira a mixture of ethyl acetate and hexane (1: 1). The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane and got to 29.5 g (61%) of product, so pl. 81 83oC>

Analysis of C23H35NO4S

Calculated: C 65,53, H of 8.37, N 3,32

Found: C 65,36, H 8,25, N 3,30

Example 31

Erythro-N-{1-[5-(1-dodecenyl)-2-thienyl]-1,3-dihydroxy-2 - propanyl}ndimethylacetamide

A solution of ethyl Erythro-2-acetamido-3-[5-1-dodecenyl)-2-thienyl]- 3-hydroxypropionate (15.0 g) in anhydrous tetrahydrofuran (150 ml) stirred at 0oC in nitrogen atmosphere, with drop adding 2M borohydride lithium in tetrahydrofuran (22,3 ml). The reaction mixture is stirred for 3 days at room temple. The residue was diluted with water (100 ml) and was extracted with ethyl acetate. The combined organic extracts were dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was purified flash chromatography on silica, elwira 1 5% methanol-ethyl acetate. The residue was recrystallized from ethyl acetate-hexane and was obtained 9.6 g (71%) of product, so pl. 83 85oC.

Analysis of C21H33NO3S:

Calculated: C 66,45, H 8,76, N 3,69

Found: C 66,47, H 8,53, N 3,75

Example 32

Erythro-2-amino-1-[5-(1-dodecenyl)-2-thienyl]-1,3-propandiol

A solution of Erythro-N-{1-[5-(1-dodecenyl)-2-thienyl]-1,3 - dihydroxy-2-propanyl} ndimethylacetamide (3.00 g), 2n sodium hydroxide (100 ml) and 95% ethanol is stirred overnight at 65oC. After cooling to room temperature, the mixture is evaporated and the residue was diluted with sodium bicarbonate solution (250 ml). The mixture was extracted with a mixture of chloroform and isopropanol (3:1) and the organic layers were combined, dried with anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was purified using flash chromatography on silica gel, elwira a mixture of dichloromethane, methanol and ammonium hydroxide (90:9:1). The appropriate fractions were combined and evaporated. The residue was led from ETHYLACETYLENE: C 67,61, H 9,26, N 4,15

Found: C 67,61, H 8,63, N 4,16

Example 33

Erythro-N-{1-[5-(1-dodecyl)-2-thienyl]-1,3-dihydroxy-2 - propane}ndimethylacetamide

A mixture of Erythro-N-{ 1-[5-(1-dodecyl)-2-thienyl] -1,3-dihydroxy-2 - propyl} ndimethylacetamide (8.00 g), 5% palladium carbon (400 mg), and absolute ethanol (500 ml) was vigorously stirred, shaking in hydrogenator Parra for 3 hours under hydrogen pressure of 50 psi (344,7 kPa). The catalyst was collected. To the filtrate was added fresh catalyst (400 mg) and the mixture is again vigorously stirred, shaking at the same time, during the night when the hydrogen pressure 50 psi (344,7 kPa). After which the mixture was filtered through a layer of celite, and the filter cake washed with ethanol. The filtrate is evaporated, and the residue was recrystallized from ethyl acetate, resulting in received (7,3 g) 90% of the product, so pl. 104 106oC.

Calculated for C21H37NO3S: C 65,75, H 9,72, N 3,65

Found: C 65,45, H 9,58, N 3,67

Example 34

Erythro-2-amino-1-[5-(1-dodecyl)-2-thienyl]-1,3-propandiol

A solution of Erythro-N-[3-[5-(1-dodecyl)-2-thienyl] -1,3-dihydroxy - 2-propyl] ndimethylacetamide (3.00 g), hydrazinoacetate (35 ml) and absolute ethanol (25 ml) stirred at 70oC and under nitrogen atmosphere for 48 hours. Then the reaction mixture ohla the Wali chloroform. The combined organic layers were dried with anhydrous sodium sulfate, and the filtrate evaporated. The residue was purified flash chromatography on silica (dichloromethane: methanol: ammonium hydroxide 90:9:1). The appropriate fractions were combined and evaporated. The residue was recrystallized from ethyl acetate: hexane and was obtained 1.4 g (52%) of product, so pl. 89 90oC.

Analysis of C19H35NO2S

Calculated: C 66,81, H 10,33, N 4,10

Found: C 66,48, H 10,37, N 4,11

Example 35

Ethyl Erythro-2-acetamido-3-(3-dodecyl-5-isoxazolyl)-3 - hydroxypropionate

A mixture of 3-dodecyl-5-isoxazolecarboxylic (5,72 g) and monoethylene of ester acetamidomalonate acid (4,06 g) in anhydrous tetrahydrofuran (75 ml) was cooled to 0oC, while stirring, was added triethylamine (to 2.29 g). The solution is evaporated and the residue was purified flash chromatography (silica gel, ethyl acetate:hexane 2:1). The appropriate fractions were collected and evaporated. After recrystallization of the residue from ethyl acetate/hexane received 4,65 g 52.6% of the product,so pl. 87 89oC.

Analysis of C22H38N2O5(%):

Calculated: C 64,36, H 8,33, N 6,82

Found: C 64,55, H remaining 9.08, N 6,76

Example 36

Erythro-N-[1-[3-(1-dodecyl)-5-isoxazolyl]-1,3-dihydroxy-the-dimethyl sulfide in dry tetrahydrofuran (70 ml) solution was added acelerado-2-acetamido-3-(3-dodecyl-5-isoxazolyl)-3-hydroxypropionate (2.4 g) in anhydrous tetrahydrofuran 20 ml). The reaction mixture was stirred at room temperature for 3 hours. The reaction was suppressed by adding a mixture of water, methanol and acetic acid (90:10:5), and was extracted with chloroform. The solution is evaporated and the residue was recrystallized twice from ethyl acetate/hexane, resulting in received of 1.23 g (57,1%) of product, so pl. 88 90oC.

Analysis: C20H36N2O4< / BR>
Calculated: C 65,19, H 9,85, N 7,60

Found: C age of 65.17, H 9,60, N 7,60

Example 37

Ethyl Erythro-2-acetamido-3-(6-bromo-2-pyridinyl)-3 - hydroksypropionat

A solution of 6-bromo-2-pyridinecarboxamide (5.6 g),complex monoethylene ether acetamidomalonate acid (5,67 g) and triethylamine (4,2 ml) in anhydrous tetrahydrofuran (40 ml) stirred at room temperature and under nitrogen atmosphere over night. The reaction mixture was evaporated and purified on a column of silica gel, elwira with a mixture of hexane and ethyl acetate (1:1), resulting received (7.9 g) 80% of the product in the form of a mixture of diastereoisomers. After recrystallization from toluene and then from ethyl acetate received 2.15 g (21,6%) of Erythro-product, so pl. 98 100oC.

Analysis of C12H15BrN2O4< / BR>
Calculated: C 43,52, H of 4.57, N 8,46

Found: C 43,56, H 4,53, N 8,42

Example 38

E. the bromo-2 - pyridinyl)-3-hydroxypropionate 11.4 g in anhydrous tetrahydrofuran (60 ml) was slowly added at 0oC and under nitrogen atmosphere 2,0 M borohydride lithium/tetrahydrofuran (20,6 ml) and the resulting mixture is stirred at room temperature overnight. Then the mixture was cooled and slowly added methanol and water (1:1), (100 ml) (100 ml), and then to bring the pH to 6.5) was added glacial acetic acid (2 ml). The mixture is evaporated, and the residue was subjected to azeotropy methanol (6 x 50 ml). The residue is suspended in 7.5% sodium bicarbonate solution (40 ml) (pH 8.5), were extracted with trichloromethane/isopropanol 3:1, was filtered, and the filtrate was concentrated. then the residue was subjected to flash chromatography on silica gel, elwira a mixture of ethyl acetate and methanol (19: 1), resulting in a received 8,9 g (93,7%) of product. After recrystallization from ethanol was obtained analytical sample Erythro-diastereoisomer, so pl. 134,5 136,5oC.

Analysis of C10H13BrN2O3< / BR>
Calculated: C 41,54, H 4,53, N RS 9.69

Found: C 41,64, H of 4.54, N FOR 9.64

Example 39

6-(1-hexadecynyl)-2-pyridinecarboxamide

A solution of 6-bromo-2-pyridinecarboxamide (12.3 g), 1-hexadecene (16,1 g), triethylamine (20,0 g), chloride bis(triphenylphosphine)palladium (II) (0,92 g), and copper iodide (I) (0,13 g) in anhydrous tetrahydrofuran (55 ml) was heated for 29 hours at 50ooC.

Analysis of C22H33NO (%):

Calculated: C 80,68. H 10,16, N 4,28

Found: C 80,44, H 10,00, N 4,30

Example 40

3-(1-dodecyl)-5-isoxazolidine

To a solution of 1-nitratireducens (10.5 g) and O-trimethylsilylpropyne (5,88 g) in anhydrous benzene (100 ml) drop by drop solution was added freshly distilled phenylisocyanate (10,9 g) and triethylamine (5,56 g) in anhydrous benzene (40 ml) at 40oC, while stirring mechanically. The mixture was heated to 60oC for 3.5 hours, and was filtered. The filtrate is evaporated, dissolved in tetrahydrofuran (300 ml) was added 1.0 M tetrabutylammonium fluoride (8 ml). After 30 min the mixture was evaporated, and the mod is ivali, the result that was obtained 10.5 g (86%) of product, so pl. 61 - 63oC.

Analysis of C16H29NO2< / BR>
Calculated: C 71,87, of 10.93 H, N 5,24

Found: C 71,92, H 11,10, N 5,19

Example 41

3-(1-dodecyl)-5-isoxazolecarboxylic

The solution oxalicacid (28.8 ml) in anhydrous dichloromethane (100 ml) was cooled to -60oC and added first a solution of dimethyl sulfoxide (8,9 ml) in dichloromethane (30 ml), and then a suspension of 3-(1-dodecyl(-5-isoxazolidinone (14.0 g) in anhydrous dichloromethane (200 ml). The resulting mixture razmeshivali -60oC for 1 hour, extinguished by triethylamine (87 ml) and left to warm to room temperature. Then the solution was poured into water (300 ml) and was extracted with dichloromethane. The organic phase was washed with diluted solution of citric acid, was dried, filtered, and the filtrate evaporated. The residue was passed through a narrow layer of silica gel, using as eluent dichloromethane. The solution is evaporated, and the residue was recrystallized from a mixture of simple ether and hexane, resulting in received of 11.5 g (78%) of product, so pl. 53 54oC.

Analysis for C16H27NO2< / BR>
Calculated: C 72,41, of 10.25 H, N 5,28

Found: C 72,22, HU 10,59, N 5,24

Example 42

Erythro-N-{1-[6-(1-hexadienyl} -3-hydroxypropionate (11.1 g) in anhydrous tetrahydrofuran (100 ml) was slowly added 2.0 M of borohydride lithium/tetrahydrofuran (11.8 ml) at 0oC and under nitrogen atmosphere. The reaction mixture was stirred 2.5 h at room temperature, cooled and slowly added a mixture of water and ethanol (1:1, 60 ml) and glacial acetic acid (1.4 ml) up until the pH is about 6.5. The mixture is then stirred 0.5 h at room temperature and evaporated. The residue was subjected to azeotropy with methanol (4 x 40 ml), suspended in 7.5% sodium bicarbonate solution (25 ml), pH 8.5, and the mixture was extracted with a mixture of chloroform and 2-propanol (3:1). The mixture was concentrated,and the residue was subjected to flash chromatography on silica gel (ethyl acetate:methanol 99:1). The appropriate fractions were collected and evaporated. After recrystallization got to 8.57 g (84.4 per cent) of the product, so pl. 88 90oC.

Analysis of C26H42N2O3< / BR>
Calculated: C 72,52, H 9,83, N 6,51

Found: C 72,55, H and 0.46, N 6,54

Example 43

Erythro-N-[1,3-deacetylase-1-(6-hexadecyl-2-pyridinyl)-2 - propenyl]ndimethylacetamide

A mixture of N-{1-[6-(1-hexadecynyl)-2-pyridinyl)]-1,3-dihydroxy - 2-propanyl} ndimethylacetamide (7,26 g, a mixture of Erythro:threo 5:2), acetic anhydride (10.5 g), triethylamine (15.5 g) and 4-dimethylaminopyridine (0.21 g) in tetrahydrofuran (100 ml) stirred over night at room temperature. Then the reaction mixture was evaporated, added metatree until while pH is not equal to 8.5. The resulting mixture was extracted with chloroform. The organic extract was dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was subjected to flash chromatography (hexane:ethyl acetate 2:1 1:1). The appropriate fractions were collected, evaporated and received 5,54 g (64%) of Erythro-N-[1,3-deacetylase-1-(6-hexadecimal-2-pyridinyl)- 2-propenyl]ndimethylacetamide.

A mixture of Erythro-N-[1,3-deacetylase-1-(6-hexadecimal-2-pyridinyl-2-propenyl] ndimethylacetamide (5,4 g) in ethanol (150 ml) and 5% palladium carbon (0.20 g) was vigorously stirred in hydrogenator Parra at hydrogen pressure of 35 pounds per square inch (241,29 kPa), for 2.5 hours. The catalyst was collected and the filtrate evaporated. The residue was chromatographically and obtained 4.1 g (75% in total 48% of the product), so pl. 79 80,5oC.

Analysis of C30H50N2O5(%):

Calculated: C 69,46, H 9,72, N 5,40

Found: C 69,81, H 9,60, N 5,41

Example 44

Erythro-N-[1-(6-hexadecyl-2-pyridinyl)-1,3-dihydroxy-2 - propanyl] ndimethylacetamide

A mixture of Erythro-N-{ 1-[6-(1-hexadecynyl)-2-pyridinyl]-1,3 - dihydroxy-2-propanyl} ndimethylacetamide (3,9 g), ethanol (125 ml) and 5% palladium carbon (0.20 g) which was in hydrogenator Parra at a pressure of 35 pounds per square inch (241,29 kPa) for 2 hours. Catacocha, so pl. 98 101oC.

Analysis of C26H46N2O3< / BR>
Calculated: C 71,85, H 10,67, N 6,44

Found: C 71,92, H 10,75, N 6,52

Example 45

Erythro-2-amino-(6-hexadecyl-2-pyridinyl)-1,3-propandiol

Erythro-N-[1-(6-hexadecyl-2-pyridinyl)-1,3-dihydroxy-2 - propanyl] ndimethylacetamide (3.0 g), hydrazine hydrate (35 ml), and ethanol (25 ml) was heated in a vessel under reflux in the presence of nitrogen for 28 hours. The reaction mixture was cooled, added to water (40 ml) and the mixture was extracted with chloroform. The combined extracts were washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was chromatographically on silica gel, elwira mixture of chloroform, methanol and 2n ammonium hydroxide (950:50:3). The appropriate fractions were collected and concentrated. The residue was dissolved in ethyl acetate, and the solution was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The residue was subjected to azeotropy toluene and got to 1.37 g (50%) of the product, so pl. 67 69oC.

Analysis of C24H44N2O2(%):

Calculated: C 73,42, 11,30 H, N 7,13

Found: C 73,25, H 11,14, N? 7.04 baby mortality

Example 46

Ethyl, threo-2 is the main monoethylene ether acetamidomalonate acid (34,1 g) and triethylamine (16.6 g) in anhydrous tetrahydrofuran (170 ml) was stirred in the presence of nitrogen at room temperature over night. The reaction mixture was concentrated, and the residue was subjected to azeotropy three times with ethyl acetate, and then recrystallized from ethyl acetate to remove of 36.4 g of ethyl Erythro-2-acetamido-3-(6-bromo-2-pyridinyl)-3-hydroxypropionate. The filtrate was chromatographically on silica gel (hexane: ethyl acetate 3:2 1:1). The appropriate fractions were collected and concentrated. The residue was recrystallized from ethyl acetate and obtained 1.0 g (2,0%) of product, so pl. 144 146oC.

Analysis of C12H15BrN2O4(%):

Calculated: C 43,52, H of 4.57, N 8,46

Found: C 44,02, H to 4.52, N 8,39

Example 47

6-(1-Undecenyl)-pyridine-2-carboxaldehyde

A solution of 6-bromopyridin-2-carboxaldehyde (15.0 g), 1-undecene (12.9 g), triethylamine (24.5 g), chloride bis(triphenylphosphine)palladium (II) (1.1 g, 2%), and copper iodide (I) (0.15 g, 1%) in anhydrous tetrahydrofuran (60 ml) was heated in the presence of nitrogen for 10 hours at 55oC. the Reaction mixture was filtered, the filter cake was rinsed with ethyl acetate: and the filtrate evaporated. The residue was dissolved in ethyl acetate, and the solution was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was subjected to flash chromatography on silica gel, 7.5 g (84,0%) of product.

Analysis of C17H23NO (%):

Calculated: C 79,33, H 9,01, N 5,44

Found: C 79,03, H 9,36, N 5,14

Example 48

Ethyl Erythro-2-acetamido-3-hydroxy-3-[6-(1-undecenyl)-2 - pyridinyl]propionate

A mixture of ethyl Erythro-2-acetamido-3-(6-bromo-2-pyridinyl)-3 - hydroxypropionate (20,8 g), 1-undecene (11.5g), triethylamine (12.7 g), chloride bis triphenylphosphine palladium (0.88 g) and copper iodide (0.12 g) in dry tetrahydrofuran (100 ml) was heated at 55oC in the presence of nitrogen for 4 hours. Then at room temperature was added 2.9 g of 1-undecene, (3.2 g), triethylamine (0,44 g) chloride bis(triphenylphosphine)palladium and (0.06 g) of copper iodide, and then the reaction mixture was heated for another 5 hours. The mixture is then evaporated, and the residue was dissolved in ethyl acetate. The solution was washed polysystem sodium chloride, and the organic phase was subjected to flash chromatography on silica gel (hexane:ethyl acetate 3:2 1:1). The appropriate fractions were collected and evaporated. After recrystallization of the residue from ethyl acetate were obtained 16.0 g (63,4%) of product, so pl. 92 93oC.

Analysis of C23H34N2O4(%):

Calculated: C 68,63, H 8,51, N OF 6.96

Found: C 68,58, H 8,54, N 6,94

Example 49

Erythro-N-{1,3-dihydroxy-1-[6-(1-undecenyl)-2-pyridinyl]-2 - propanyl}ndimethylacetamide

To ethyl obavljale 2,0 M borohydride lithium/tetrahydrofuran(22 ml) at 0oC and in the presence of nitrogen. Then the reaction mixture was cooled, stirred overnight at room temperature and added water first with methanol (1:1) (30 ml), and then glacial acetic acid (2.8 ml) in a mixture of methanol water (1:1), (30 ml) up until the pH is not equal to 6.4. The resulting solution was stirred at room temperature for 1 hour, then evaporated and the residue was subjected to azeotropy methanol. Then the residue is suspended in 7.5% sodium bicarbonate solution (pH 8.5), was extracted with chloroform and 2-propanol (3:1), and concentrated. The residue was subjected to flash chromatography on silica gel (0.5% of 1% methanol:ethyl acetate). The appropriate fractions were collected and concentrated. After recrystallization of the residue from a mixture of hexane and ethyl acetate (1:1) was obtained 12.1 g (75,4%) of product, so pl. 95 96,5oC.

Analysis of C21H32N2O3(%):

Calculated: C 69,97, H 8,95, N TO 7.77

Found: C 69,84, H 8,87, N 7,71

Example 50

(Z)-Erythro-N-{ 1,3-dihydroxy-1-[6-(1-octenyl)-2-pyridinyl]- 2-propanyl} ndimethylacetamide

A solution of ethyl Erythro-2-acetamido-3-[6-(1-octenyl)-2 - pyridinyl]-3-hydroxypropionate (9,9 g) in dry tetrahydrofuran (80 ml) and 2.0 M borohydride lithium/tetrahydrofuran (12.5 ml) stirred at 0oC p is obavljale mixture of methanol and water (1:1), (40 ml), and acetic acid was added (1.5 ml) to obtain a pH of 6.8. Then the reaction mixture is stirred for 1 hour, evaporated, and the residue was subjected to azeotropy methanol. Then added 7.5% sodium bicarbonate solution to obtain a pH of 8.5. The mixture was extracted with chloroform: 2-propanol (3:1) and concentrated. The residue was subjected to flash chromatography on silica gel, elwira 1% methanol/ethyl acetate, and obtained 7.6 g of product.

Part of the obtained product (5.0 g) and 8,35 g from another similar experiment (25,7 g) of acetic anhydride, (38,2) and triethylamine (0.51 g) 4-dimethylaminopyridine in tetrahydrofuran (180 ml) was stirred 3 hours at room temperature. The reaction mixture was evaporated, added methanol, the resulting mixture was heated at 50oC for 20 minutes and evaporated. Then added 7.5% sodium bicarbonate solution to obtain a pH of 8.5, and the mixture was extracted with chloroform. The extract was dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was subjected to flash chromatography hexane:ethyl acetate 2:1. The appropriate fractions were collected and concentrated, resulting in the obtained (Z)-Erythro-N-{1,3 - deacetylase-1-[6-(1-octenyl)-2-pyridinyl]-2-propanyl}ndimethylacetamide.

The solution a. The reaction mixture was filtered, and filtercontrol. The residue was chromatographically on silica gel with 0.5% methanol/ethyl acetate. The appropriate fractions were collected and concentrated, resulting in a received 0.5 g (3.7% of total) product.

Analysis of C18H28N2O3(%):

Calculated: C 67,47, H 8,81, N, a total of 8.74

Found: C 67,60, H 8,96, N 8,72

Example 51

Erythro-N-[1,3-deacetylase-(6-octyl-2-pyridinyl)-2 - propenyl]ndimethylacetamide

A solution of Erythro-N-{1,3-dihydroxy-1-[6-(1-octenyl)-2 - pyridinyl]-2-propanyl} ndimethylacetamide (13,4 g), acetic anhydride (25,7 g), triethylamine (38,2 g) and 4-dimethylaminopyridine (0.51 g) in tetrahydrofuran (180 ml) was stirred at room temperature for 3 hours. Then the reaction mixture is evaporated, add methanol to the residue, and the resulting solution was heated at 50oC for 20 minutes and evaporated. Then add 7.5% sodium bicarbonate solution to obtain a pH of 8.5, and the mixture was extracted with chloroform. The extract was dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was subjected to flash chromatography (hexane: ethyl acetate 2:1 1:1). The appropriate fractions were collected, evaporated and received 9,17 g of Erythro-N-1,3-deacetylase-1-(6-octenyl-2-pyridinyl)-2-propenyl) acetaminophenxycodone Parra at hydrogen pressure of 40 pounds per square inch (275,76 kPa). After 1.5 hours, the catalyst was collected, and the filtrate evaporated. The residue was chromatographically and obtained 6.0 g (78.5% of total 43%) of product, so pl. 53 56oC.

Analysis of C22H34N2O5< / BR>
Calculated: C 65,00, H 8,43, N 6,89

Found: C 65,07, H 8,32, N 6,88

Example 52

Erythro-N-[1,3-dihydroxy-1-(6-octyl-2-pyridinyl)-2-propenyl] ndimethylacetamide

A solution of Erythro-N-[1,3-dietlose-1-(6-octyl-2-pyridinyl-2 - propenyl] ndimethylacetamide (5,2 g) and potassium carbonate (0.88 g) in methanol (75 ml), stirred for 1 h, the Precipitate was collected, and the filtrate evaporated. Then added 7.5% sodium bicarbonate solution and 1N hydrochloric acid to obtain a pH of 8.5. Then the mixture was extracted with a mixture of chloroform and 2-propanol (3:1). The extract was dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. After recrystallization of the residue from ethyl acetate were obtained 3.1 g of product (75,6%), so pl. 86,5 85oC.

Analysis of C18H30N2O3(%):

Calculated: C 67,05, H 9,38, N 8,69

Found: C 66,98, H 9,74, N 8,65

Example 53

Erythro-2-amino-1-(6-octyl-2-pyridinyl)-1,3-propandiol.

A solution of Erythro-N-[1,3-dihydroxy-1-(6-octyl-2-pyridinyl)-2 - propenyl] ndimethylacetamide(3.8 g), hydrazine hydrate is added (35 ml), and ethanol (25 ml) was heated in SES was extracted with chloroform. The extract was washed with saturated sodium chloride, dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The residue was chromatographically on silica gel (chloroform:methanol:2n. the ammonium hydroxide 950:50:3). The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate, and the solution was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The residue was subjected to azeotropy toluene and received 2,47 g (75%) of product, so pl. 38 - 40oC.

Analysis of C16H28N2O20,1 H2O (%):

Calculated: C 68,10, H 10,07, N TO 9.93

Found: C 67,88, H 10,18, N 9,74

Example 54

Threo-2-amino-1-(6-octyl-2-pyridinyl)-1,3-propandiol

A mixture of Erythro - and threo-N-{1,3-dihydroxy-1-[6-(1-octenyl)-2 - pyridinyl]-2-propanyl} ndimethylacetamide (13,4 g), acetic anhydride (25,7 g), triethylamine (38,2 g) and 4-dimethylaminopyridine (0.5 g) in tetrahydrofuran (180 ml) was stirred 3 h at room temperature. Then the reaction mixture is evaporated and the residue was heated with methanol (80 ml) for 20 minutes, and the resulting mixture evaporated. Then added 7.5% sodium bicarbonate solution to obtain a pH of 8.5, and the resulting solution was extracted with chloroform. Extract collected and evaporated, the result that was obtained 2.4 g (14%) threo-N-{1,3-deacetylase-1-[6-octenyl)-2-pyridinyl]-2-pyridinyl] - 2-propanyl}ndimethylacetamide. (2.4 g) of this compound in ethanol (75 ml) containing 0.12 g of 5% palladium charcoal, vigorously stirred in hydrogenator Parra at a pressure of 40 pounds per square inch (275,76 kPa). After 3 hours the reaction mixture was filtered, and the filtrate evaporated. The residue was subjected to flash chromatography. The appropriate fractions were collected and evaporated, resulting in a received threo-N-{1,3-deacetylase-1-[6-octyl-2-pyridinyl]-2 - propane}ndimethylacetamide (2.2 g), (92%).

The solution of threo-N-[1,3-deacetylase-1-(6-octyl)-2-pyridinyl)- 2-propenyl] ndimethylacetamide (2.17 g) is stirred with potassium carbonate (70 mg) and methanol (25 ml) for 1 hour at room temperature, was filtered, and the filtrate evaporated. Then add water, the pH was brought to 8.5 and the mixture was extracted with a mixture of chloroform and 2-propanol (3:1). The extract was concentrated and was obtained 1.6 g (94%) threo-N-[1,3-deacetylase-(6-octyl-2 - pyridinyl)-2-propenyl]ndimethylacetamide so pl. 71,5 74oC.

A solution of 1.6 g of the obtained compound, 15 ml of hydrazine hydrate is added, and ethanol (15 ml) was heated in a vessel under reflux in the presence of nitrogen for 23 hours. Reactionuses was cooled, then dobashi anhydrous magnesium sulfate, was filtered, and the filtrate evaporated. The residue was chromatographically on silica gel (chloroform:methanol:2n. the ammonium hydroxide 960:40:3). The appropriate fractions were collected and evaporated, resulting in a received 0,78 g (56,5% 7,0%) of product, so pl. 74 - 77oC.

Analysis of C16H28N2O2(%):

Calculated: 68,53, H 10,06, N 9,99

Found: 68,48, H 10,15, N 9,96

Example 55

Erythro-2-amino-1-(6-hexyl-2-pyridinyl)-1,3-propandiol

A solution of Erythro-2-[1-(6-hexyl-2-pyridinyl)-1,3-dihydroxy-2 - propanyl] ndimethylacetamide (3.6 g), hydrazine hydrate is added (35 ml), and ethanol (25 ml) was heated in a vessel under reflux in the presence of nitrogen within 29 hours. The reaction mixture was cooled, added to water (50 ml), and extracted with ethyl acetate. The extracts were washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The residue was chromatographically on silica gel (chloroform:methanol:2n. the ammonium hydroxide 950: 50: 3). The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate (80 ml) and the solution was washed polysystem solution of sodium chloride, dried, filtered, and the filtrate is evaporated, resulting in a received 2,02 g 66% of the product.

BR>
6-(7-phenyl-1-heptenyl)pyridine-2-carboxyaldehyde

A solution of 6-bromopyridin-2-carboxaldehyde (30.0 g), 7-phenyl-1-Heptene (26,8 g), triethylamine (48,9 g) chloride bis(triphenylphosphine) palladium (II) (2.3 g, 2% ), and copper iodide (0.31 g, 1%) in anhydrous tetrahydrofuran (100 ml) was heated in the presence of nitrogen at 55oC for 70 hours. The reaction mixture was cooled to room temperature. Was filtered and the filtrate was washed with ethyl acetate. Then the filtrate is evaporated. The residue was dissolved in ethyl acetate, the solution washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, and the filtrate was concentrated. The residue was subjected to flash chromatography on silica gel, elwira 0,5% 2% ethyl acetate:hexane. The appropriate fractions were collected and concentrated, resulting in received of 29.5 g of the product.

Analysis of C19H19NO

Calculated: C 82,28, H 6,90, N OF 5.05

Found: C 82,00, H 6,94, N 5,02

Example 57

Ethyl Erythro-2-acetamido-3-hydroxy-3-[6-(7-phenyl-1-heptenyl) 2-pyridinyl]propionate

A solution of 6-(7-phenyl-1-heptenyl)pyridine-2-carboxaldehyde (26.5 g), complex monoethylene ether acetamidomalonate (19.2 g), triethylamine (14.6 ml) in anhydrous tetrahydrofuran (125 ml) is stirred 3 days at room for the EOS washed polysystem solution of sodium chloride, was dried with anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographically on a column of silica gel (hexane:ethyl acetate 1: 1) and got to 32.9 g (82,0%) of a mixture of Erythro - and threo-isomers. After recrystallization of the mixture from a mixture of hexane and ethyl acetate (1:1) was obtained 4.7 g (11,5%) of product, so pl. 79 81oC.

Analysis of C25H30N2O4(%):

Calculated: C 71,07, H 7,16, N 6,63

Found: C 71,27, H 6,89, N 6,63

Example 58

Erythro-N-{ 1,3-dihydroxy-1-[6-(7-phenyl-1-heptenyl)-2 - pyridinyl]-2-propanyl}ndimethylacetamide

To a solution of ethyl Erythro-2-acetamido-hydroxy-3-]6-(7-phenyl - 1-pectineal)-2-pyridinyl] propionate (23,4 g) in anhydrous tetrahydrofuran (200 ml) was added 2.0 M of borohydride lithium/tetrahydrofuran (22 ml) at 0oC in the presence of nitrogen. Then the reaction mixture was stirred at room temperature overnight, cooled, and added a mixture of methanol and water (1:1), (50 ml) and then glacial acetic acid (2.5 ml) in methanol and water (11:1), (30 ml) to obtain a pH of 6.4. The solution is stirred at room temperature for 1 hour, evaporated, and the residue was subjected to azeotropy methanol. The residue is suspended by sodium bicarbonate (40 ml)pH of 8.5, a saturated solution of sodium chloride, and then the mixture was extracted CHL is (0,5% 5% methanol:ethyl acetate). The appropriate fractions were collected and evaporated. After recrystallization from a mixture of hexane and ethyl acetate (1:1) received 2.64 g (34%) of product, 83 - 85oC.

Analysis of C23H28N2O3(%):

Calculated: C 72,62, H 7,42, N OF 7.36

Found: C 72,75, H 7,66, N 7,31

Example 59

Ethyl Erythro-2-acetamido-3-hydroxy-3-[6-(5-phenyl-1-pentenyl) -2-pyridinyl]propionate

A mixture of ethyl Erythro-2-acetamido-3-(6-bromo-2-pyridinyl)-3 - hydroxypropionate (23,2 g), 5-phenyl-1-pentyne (12.1 g), triethylamine (10.6 g), chloride bis(triphenylphosphine)palladium (0,98 g) and copper iodide (0,13 g) in anhydrous tetrahydrofuran (100 ml) was heated for 1.5 hours at 55oC in the presence of nitrogen. Then was added to 6.1 g of 5-phenyl-1-pentyne and 7.1 g of triethylamine, (0,49 g) chloride bis triphenylphosphine palladium, and (0.07 g) of copper iodide, and the resulting reaction mixture was heated overnight. Then the reaction mixture was filtered and the filtrate evaporated. The residue was dissolved in ethyl acetate, washed polysystem solution of sodium chloride and perform flash chromatography on silica gel, elwira with a mixture of hexane and ethyl acetate (1:1). The appropriate fractions were collected. Ostateczna was chromatographically, elwira 1% methanol:chloroform, and obtained 14.2 g (51,6%) of product.

Analysis

Erythro-N-{ 1,3-dihydroxy-1-[6-(5-phenyl-1-pentenyl)-2 - pyridinyl]-2-propanyl}ndimethylacetamide

To a solution of ethyl Erythro-2-acetamido-3-hydroxy-3-[6-5-phenyl - 1-pentenyl)-2-pyridinyl)propionate 12.3 g in anhydrous tetrahydrofuran (100 ml) was added 2.0 M of borohydride lithium/tetrahydrofuran (15,5 ml) at 0oC and in the presence of nitrogen. The reaction mixture was stirred at room temperature overnight, cooled and added methanol and water (1:1), (45 l) and glacial acetic acid (1.8 ml) to obtain a pH of 6.5. The mixture is then stirred for 80 minutes at room temperature. Then the reaction mixture was evaporated, the residue was subjected to azeotropy methanol and suspended (7,5%) sodium bicarbonate solution (25 ml, pH 8.5). The mixture was extracted with a mixture of chloroform and 2-propanol (3:1), filtered, and the filtrate was concentrated. The residue was subjected to flash chromatography on silica gel with 0.5% 1% methanol:ethyl acetate. The appropriate fractions were collected and concentrated, resulting in the 6.0 g (54,6%) of product, so pl. 91 95oC.

Analysis of C12H24N3O3(%):

Calculated: C 71,57, H 6,86, N OF 7.95

Found: C 71,48, H is 6.75, N 7,92

Example 61

Erythro-N-{ 1,3-dihydroxy-1-[6-(freepanty)-2-pyridinyl]- 2-propanyl} ndimethylacetamide hydrate

Erythro-N-{1,3-is consistent charcoal (0.20 g) and vigorously stirred in hydrogenator Parra at hydrogen pressure of 40 pounds per square inch (275,76 kPa). After 1.5 hours, the catalyst was collected. The filtrate is evaporated and the residue was chromatographically on silica gel (0.5% of 1% methanol:ethyl acetate), to deliver 2.8 g (50%) of the product.

Analysis of C21H28N2O3H2O3< / BR>
Calculated: C 67,36, H 8,07, N OF 7.48

Found: C 67,95, H 8,02, N 7,53

Example 62

Erythro-2-amino-1-[6-(5-fenilpentil)-2-pyridinyl] -1,3 - propane diol hemihydrate

A solution of Erythro-N-{ 1,3-hydroxy-1-[6-(5-fenilpentil)-2 - pyridinyl]-2-propanyl}ndimethylacetamide (3.5 g), hydrazine hydrate is added (32 ml), and ethanol (25 ml) was heated in a vessel under reflux in the presence of nitrogen for 26 hours. The reaction mixture was cooled, added to water (40 ml) and the mixture was extracted with chloroform. The extracts were washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The mixture of residue and 0.25 g of a similar experiment was chromatographically on silica gel(chloroform: methanol:2n ammonium hydroxide 950:50:3). The appropriate fractions were collected and evaporated. The residue was dissolved in chloroform (100 ml) and the solution was washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was dried at 702O (%):

Calculated: C 70,56, H to 8.41, N 8,66

Found: C 70,77, H 8,23, N 8,62

Example 63

Erythro-N-{1,3-dihydroxy-1-[3-(1-undecenyl)phenyl]-2 - propanyl}ndimethylacetamide

To ethyl Erythro-2-acetamido-3-hydroxy-3-[3-1-undecylenic the propionate] (7,3 g) in dry tetrahydrofuran (75 ml) was added 2.0 M of borohydride lithium/tetrahydrofuran (11,4 ml) at 0oC in the presence of nitrogen. The reaction mixture was cooled, stirred at room temperature overnight, and one drop was added to a mixture of glacial acetic acid (1.3 ml), methanol (25 ml) and water (25 ml) to obtain a pH of 6. Then the solution was concentrated and the residue was extracted with ethyl acetate. The extracts were dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated. After grinding residue with a simple mixture of ether and hexane (2:3) and recrystallization from ethyl acetate were obtained 1.9 g (29%) of product, so pl. 99 101oC.

Analysis of C22H33NO3(%):

Calculated: C 73,50, H a 9.25, N 3,90

Found: C 73,56, H 9,05, N 3,93

Example 64

Erythro-N-{1-[3-(1-dodecyl)phenyl]-1,3-dihydroxy-2-propanyl} ndimethylacetamide

To ethyl Erythro-2-acetamido-3-[3-(1-dodecenyl)phenyl]-3 - hydroxypropionate (24,0 g) in tetrahydrofuran (220 ml) was added 2n. borohydride lithium/tetrahydrofuran (29 ml), with 2oC, the Yali mixture of methanol and water (1:1), (100 ml) and glacial acetic acid (3.3 ml) to obtain a pH of 6.5. And the solution was stirred at room temperature for 0.5 hours, evaporated, and the residue was subjected to azeotropy methanol. Then the residue is suspended in 7.5% sodium bicarbonate solution 50 ml, pH 8.5, and the mixture was extracted with chloroform, and propanol (3:1). The extract was concentrated. The residue was subjected to flash chromatography on silica gel, elwira with ethyl acetate. The appropriate fractions were collected and evaporated. After recrystallization of the residue from ethyl acetate received 9,13 g (42.4%) of product, so pl. 93 95oC.

Analysis of C23H35NO3< / BR>
Calculated: C 73,96, H 9,44, N 3,75

Found: C 73,66, H 9,14, N 3,69

Example 65

Erythro-N-[1-(3-dodecylphenyl)-1,3-dihydroxy-2-propanyl] ndimethylacetamide

Erythro-N-[1-(3-dodecyl)phenyl]-1,3-dihydroxy-2-propanyl the ndimethylacetamide (4.4 g) in ethanol (100 ml) containing 5% palladium carbon (0.02 g) was vigorously which in hydrogenator Parra at a pressure of 35 pounds per square inch (241,29 kPa) for 2.5 hours. The catalyst was collected, the solvent evaporated, and the residue was recrystallized from ethyl acetate, which was obtained 4.1 g (90,6%) of product, so pl. 101 104oC.

Analysis of C23H39NO3< / BR>
Calculated: C 73,17, H 10,41, 3,7 N[1-(3-dodecylphenyl)-1,3-dihydroiso-2-propenyl] ndimethylacetamide (2.9 g), hydrazinehydrate (25 ml), and ethanol (25 ml) was heated in a vessel under reflux in the presence of nitrogen for 22 hours. The reaction mixture was washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was chromatographically on silica gel (chloroform: methanol: 2n ammonium hydroxide 950:50:3). The appropriate fractions were collected and evaporated. The residue was dissolved in ethyl acetate (75 ml) and the solution was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, evaporated, and the residue was subjected to azeotropy toluene, resulting in a received 1.35 g (52%) of product, so pl. 36 40oC.

Analysis of C21H37NO2(%):

Calculated: C 75,17, H, 11,12, N 4,17

Found: C 75,14, H 11,18, N 4,12

Example 67

Erythro-N-[1-[5-(1-dodecyl)-2-thienyl]-1,3-diacetoxy-2 - propyl]ndimethylacetamide

A solution of Erythro-N-[1-[5-(1-dodecyl)-2-thienyl]-1,3-dihydroxy - 2-propyl] ndimethylacetamide (12.0 g), acetic anhydride (19.2 g), triethylamine (28.4 g), and dimethylaminopyridine (0.4 g) in anhydrous tetrahydrofuran (150 ml) stirred at room temperature for 3 hours. The reaction mixture is evaporated, and the residue was dissolved in chloroform. The solution was washed with water, drained, filter25H41NO5S:

Calculated: C 64,21, H 8,84, N, 2,99

Found: C 64,33, H 8,92, N 3,02

Example 68

Ethyl Erythro-2-ndimethylacetamide-3-[5-(1-nonenal)-2-thienyl]-3 - hydroxypropionate

A suspension of 5-nonenal-2-thiophenecarboxaldehyde (40,0 g),complex monoethylene ether acetamidomalonate acid (32,3 g) and anhydrous tetrahydrofuran (150 ml) was degirolami and was cooled to 0oC. Then was added triethylamine (18.2 g), the solution was degirolami, and the reaction mixture stirred 4 days at room temperature in the presence of nitrogen. Then added a complex monotropy ether of acetamidomalonate acid (32,3 g), and triethylamine (18.2 g) and the reaction mixture stirred 4 days at room temperature in the presence of nitrogen. After which the mixture is evaporated and the residue was dried in vacuum. The residue was subjected to flash chromatography (silica, ethyl acetate:hexane 1:1). The appropriate fractions were collected and evaporated. The residue was led from the ether, then recrystallized twice from ethyl acetate and resulted 40,2 g 62% of the product, so pl. 104 106oC.

Analysis: C20H29NO4(%):

Calculated: C 63,30, H of 7.70, N 3,69

Found: C 63,30, H of 7.64, N 3,71

Example 69

Erythro-N-[1-[5-(1-nonenal)-2-thienyl]-1,3-dihydroxy-2 - propyl]AC is rageragerage (150 ml) stirred under nitrogen atmosphere at 0oC, drop by drop adding borohydride lithium (2.0 M in tetrahydrofuran). The reaction mixture was stirred over night under nitrogen atmosphere, heating to room temperature. Stemball solution of methanol, water and acetic acid(50:50:8), (108 ml) while cooling in an ice bath. The solution was neutralized glacial acetic acid and evaporated. The residue was diluted with water and extracted with ethyl acetate. The combined organic extracts were dried with anhydrous sodium sulfate, filtered, and the filtrate evaporated. The residue was subjected to flash chromatography (silica, 2 to 4% methanol:ethyl acetate). The appropriate fractions were collected and evaporated. The residue was recrystallized twice from ethyl acetate and received a 29.9 g (84%) of product, so pl. 81 83oC.

Analysis of C18H27NO3S

Calculated: C 64,06, H of 8.06, N 4,15

Found: C 64,04, H 8,17, N 4,16

Example 70

Erythro-2-amino-1-[5-(1-nonenal)-2-thienyl]-1,3-propandiol

A solution of Erythro-N-[1-[5-(nominal)-2-thienyl]-1,3-dihydroxy - 2-propyl]ndimethylacetamide (16.4 g), 2n sodium hydroxide (150 ml), and 95% ethanol (75 ml) was stirred overnight at 70oC. the Reaction mixture was cooled to room temperature and acidified glacial acetic acid. The solution was diluted with water (200 ml), is hloroform and 2-propanol (4:1). The combined organic extracts were dried with anhydrous sodium sulfate, filtered, and the filtrate evaporated. The residue was combined with the precipitate and led flash chromatography (silica,dichloromethane:methanol:ammonium hydroxide 90: 9: 1), resulting in received of 11.8 g (82%) of product. Part of the product has led from simple ether and obtained the analytical sample, so pl. 64 67oC.

Analysis of C16H25NO2S,

Calculated: C 65,05, H 8,53, N 4,74

Found: C, 65.22 per, H 8,56, N 4,76

Example 71

Erythro-N-{1-[5-(1-nonyl)-2-thienyl]-1,3-dihydroxy-2-propyl} ndimethylacetamide

A mixture of Erythro-N-{1-[5-/1-nominal/-2-thienyl]-1,3-dihydroxy-2 - propyl}ndimethylacetamide /8.00 g/, 5% palladium charcoal /800 g/, and absolute ethanol 500 ml of vigorously stirred in hydrogenator when the hydrogen pressure of 50 psi /344,7 kPa/ during the night. The catalyst was filtered through a pad of celite, and the filtrate was washed with ethanol. The filtrate is evaporated, and the residue was recrystallized twice from ethyl acetate and obtained 7.0 g /86%/ product, so pl. 98 100oC.

Analysis of C18H31NO3S /%/:

Calculated: C 63,31, H 9,15, N 4,1

Found: C 63,03, H 9,14, N 4,01

Example 72

5-/6-phenyl-1-hexenyl/-2-thiophenecarboxaldehyde

Rurale /75 ml/ degirolami and stirred pikantnoi temperature in the presence of nitrogen. Then was added 2M chloride bis/triphenylphosphine/Palladin /II/ /2.7 g/, then 1 M of copper iodide /I/ /0.4 g/. The mixture was degirolami and stirred at room temperature in the presence of nitrogen during the night. The precipitate was filtered and washed with ethyl acetate. The filtrate is evaporated, the residue was distilled and received and 47.0 g /91% / product. Part of the product /2 g/ subjected to flash-chromatography /dioxide sodium, toluene:hexane 1:1/. The appropriate fractions were collected and evaporated. The residue was distilled at 170oC/0.07 mm RT.article and obtained an analytical sample in the form of butter.

Analysis: C17H16OS

Calculated: C 76,08, H 6,01

Found: C 75,54, H 6,04

Example 73

Erythro-N-{ 1-[5-/6-phenyl-1-hexenyl/-2-thienyl]-1,3-dihydroxy-2-propyl} ndimethylacetamide

A solution of ethyl Erythro-2-acetamido-3-[5-/6-phenyl-1-hexenyl/-2 - thienyl]-3-hydroxypropionate /41,6 g/ in anhydrous tetrahydrofuran /150 ml stirred at 0oC in the presence of nitrogen with one drop of adding a solution of lithium borohydride 2.0 M in tetrahydrofuran, /66 ml/. The reaction mixture was heated to room temperature and stirred for 4 hours in the presence of nitrogen. Then, while cooling in an ice bath was added a solution of methanol, water and acetic acid 50:50:8, 108 ml/. Then added ice the United organic extracts osullivanm sodium sulfate, was filtered and the filtrate evaporated. The residue was subjected to flash-chromatography /silica, dichloromethane:methanol:2n ammonium hydroxide 90:9:1/. The appropriate fractions were cooled and evaporated. After recrystallization from ethyl acetate received 31,5 /84%/ product, so pl. 131 133oC.

Analysis of C21H25NO>3S

Calculated: C 67,90, H is 6.78, N OF 3.77

Found: C 67,54, H 6,88, N 3,71

Example 74

Erythro-2-amino-1-[5-/6-phenyl-1-hexenyl/-2-thienyl]-1,3 - propandiol

A solution of Erythro-N-[1-[5-/6-phenyl-1-hexenyl/-2-thienyl]-1,3 - dihydroxy-2-propyl] ndimethylacetamide /10.0 g/, 1N solution of sodium hydroxide /125 ml/ 95% ethanol /75 ml/ stirred overnight at 65oC. the Reaction mixture is evaporated and the residue was neutralized glacial acetic acid. The solution was diluted with water to 200 ml and was extracted with chloroform: 2-propanol /4:1/. The combined organic extracts were dried with anhydrous sodium sulfate, filtered, and the filtrate evaporated. The residue was subjected to flash-chromatography /silica, dichloromethane:methanol:2n ammonium hydroxide 90:9:1/. The appropriate fractions were collected and evaporated, resulting in a received 7,8 g /88% / product. Part of the product has led from ethyl acetate and hexane and obtained analytical about the>/BR>Found: C 69,29, H 7,14, N 4.26 DEATHS

Example 75

4-/1-dodecenyl/-2-thiophenecarboxaldehyde

A solution of 1-dodecene /23,9 g/, 5-bromo-2 - thiophenecarboxaldehyde /25,0 g/, triethylamine and 39.7 g/ in anhydrous tetrahydrofuran /75 ml/ degirolami and stirred at room temperature and in the presence of nitrogen. Then added 2 M chloride bis/triphenylphosphine/palladium /1.8 g/, then 1 M of copper iodide /I/ /0.25 g/. The mixture was degirolami and stirred 3 days at room temperature and in the presence of nitrogen. The precipitate was filtered, and the filter cake was washed with ethyl acetate. The filtrate is evaporated, and the residue was subjected to flash-chromatography /silica, hexane:dichloromethane 7:3/. The appropriate fractions were collected and evaporated. The residue was dried at 50oC in vacuum for 3 hours, and got 35.5 g /98%/ product.

Analysis of C17H24OS /%/:

Calculated: C 73,86, H 8,75

Found: C 73,79, H remaining 9.08

Example 76

Ethyl Erythro-2-acetamido-3-[4-/1-dodecenyl/-2-thienyl]-3 - hydroxypropionate

A suspension of 4-/1-dodecenyl/-2-thiophenecarboxaldehyde/21,4 g/, complex monoethylene ether acetamidomalonate acid /14.6 g/, and anhydrous tetrahydrofuran /100 ml was degirolami and was cooled to 0oC. Then was added triethylamine /8,23 g/, and the solution alali another 14.6 g complex monoethylene ether acetamidomalonate acid and 8,23 g of triethylamine, and the reaction mixture is stirred for 5 days at room temperature in the presence of nitrogen. After which the mixture is evaporated, the residue was dried in vacuum, and were flash-chromatography /silica, hexane:ethyl acetate 3:2/. The appropriate fractions were collected and evaporated. The residue was recrystallized from a mixture of ethyl acetate and hexane and received 23.3 g /71%/ product, so pl. 79 81oC.

Analysis of C23H35NO4S /%/:

Calculated: C 65,53, H of 8.37, N 3,32

Found: C 65,63, H of 7.96, N 3,34

Example 77

Erythro-2-amino-1-[4-/1-dodecyl/-2-thienyl]-1,3-propandiol

A solution of Erythro-N-[1-[4-/dodecyl/-2-thienyl]-1,3-dihydroxy-2 - propyl]ndimethylacetamide /6,35 g/ 2n sodium hydroxide /100 ml 95% ethanol /50 ml/ stirred overnight at 65oC. the Reaction mixture was cooled to room temperature and neutralized glacial acetic acid. Then the solution was diluted with water to 200 ml and cooled. The precipitate was collected, and the filtrate was extracted with chloroform. The combined organic extracts were dried with anhydrous sodium sulfate, and filtered, and the filtrate evaporated. The residue was combined with the precipitate and subjected to flash-chromatography /silica, dichloromethane: methanol: 2n ammonium hydroxide 90:9:1/. Appropriate fracc is UP>oC.

Analysis of C19H35NO2S

Calculated: C 66,81, H 10,33, N 4,10

Found: C 66,70, the 10.40 H, N 4,11

Example 78

Ethyl Erythro-2-acetamido-3-[5-/6-phenyl-1-hexenyl/-2-thienyl] -3-hydroxypropionate

A suspension of 6-phenyl-1-hexenyl-2-thiophenecarboxaldehyde /45,0 g/, complex monoethylene ether acetamidomalonate acid and 31.7 g/ dry tetrahydrofuran /150 ml/ degirolami and was cooled to 0oC. Then was added 17.9 g of triethylamine, and the resulting solution was degirolami, and the reaction mixture was stirred 2 days at room temperature in the presence of nitrogen. Then was added and 31.7 g of complex monoethylene ether acetamidomalonate acid and 17.9 g of triethylamine, and the reaction mixture stirred at room temperature in the presence of nitrogen for 2 more days. The mixture is evaporated, the residue was dried in vacuum, and were flash-chromatography /silica, ethyl acetate:hexane 1:1/. The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane received 48,1 g /69%/ product, so pl. 90 92oC.

Analysis of C23H27NO4S:

Calculated: C 66,80, H to 6.58, N 3,39

Found: C 66,48, H 6,59, N 3,33

Example 79

Erythro-2-amino-1-[4-/1-dodecenyl/-2-thienyl]-1,3-propandiol ACE is /100 ml, 95% ethanol 50 ml stirred overnight at 65oC. Then the reaction mixture was cooled to room temperature, and acidified glacial acetic acid. The solution was diluted with water to 200 ml and cooled in the refrigerator. The precipitate was collected, and the filtrate was extracted with chloroform. The combined organic extracts were dried with anhydrous sodium sulfate, filtered, and the filtrate evaporated. The residue was combined with the precipitate obtained earlier, and recrystallize twice from ethyl acetate, which was obtained 4.0 g /55%/ product, so pl. 120 122oC.

Analysis of C21H35NO2S

Calculated: C 63,44, H 8,87, N 3,52

Found: C 63,32, H 8,71, N 3,50

Example 80

Erythro-N-[1-[4-/1-dodecyl/-2-thienyl]-1,3-dihydroxy-2 - propyl]ndimethylacetamide

A mixture of Erythro-N-[1-[4-/1-dodecyl] -2-thienyl-1,3-dihydroxy - 2-propyl] ndimethylacetamide /8.00 g/, 5% palladium charcoal /800 ml) and absolute ethanol /500 ml/ sbaltimore hydrogen pressure of 50 psi /344,7 kPa/ during the night. The reaction mixture was filtered through a pad of cellite, and the filter cake washed with ethanol. The solvent is evaporated and the residue recrystallized twice from ethyl acetate, and obtained 7.0 g /87%/ product, so pl. 92 94oC.

Analysis of C21what about the-1-[3-/1-dodecyl/-5-isoxazolyl]-1,3 - propandiol

A solution of Erythro-N-[1-[3-/1-dodecyl/-5-isoxazolyl] -1,3 - dihydroiso-2-propyl]ndimethylacetamide /4.0 g/, degassed 2n solution of sodium hydroxide /100 ml, and 95% ethanol /50 ml/ stirred 3 hours at 60oC. the Reaction mixture was concentrated, the residue was diluted with sodium bicarbonate solution, and was extracted with chloroform/2-propanol 4:1. The combined organic extracts were dried with anhydrous magnesium sulfate, filtered and the filtrate evaporated. The residue was recrystallized from ethyl acetate-hexane. The precipitate was subjected to flash-chromatography /silica, dichloromethane:ethanol 90:1/. The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane and was obtained 2.3 g /65%/ product, so pl. 88 90oC.

Analysis of C18H34N2O3/%/

Calculated: C 66,22, H 10,50, N 8,58

Found: C 65,55, H 10,44, N 8,51

Example 82

3-/1-dodecyl/-5-isoxazolidine

To a solution of 1-nitrohexane /38.0 g/ About-trimethylsilylpropyne /24,1 g/ in anhydrous benzene /300 ml) was added one drop of freshly distilled phenylisocyanate /44,9 g/ and triethylamine /22,4 g/ in anhydrous benzene /50 ml, stirring at 40oC. the Reaction mixture was heated for 3 hours at 60oC, then cooled and filtered. the Ali flash chromatography silica gel, 1% methanol-dichloromethane and got 15.5 g /34%/ product, so pl. 55 56oC.

Analysis of C14H25NO2/%/:

Calculated: C 70,25, H 10,53, N 5,85

Found: C 70,44, H 10,42, N OF 5.92

Example 83

3-/1-decyl/-5-isoxazolecarboxylic

To a solution of oxalicacid /31.7 oz/ in anhydrous dichloromethane /100 ml, cooled to -60oC, was added a solution of dimethylsulfoxide /9,8 ml/ dichloromethane /30 ml/, and then a suspension of 3-/1-decyl/-5-isoxazolidinone /13.8 g/ in anhydrous dichloromethane /100 ml. The reaction mixture is stirred at -60oC for 0.5 hours, and then extinguished by the addition of triethylamine /40 ml/, and left to warm to room temperature. The solution was poured into water /300 ml and was extracted with dichloromethane. The organic phase was washed with razbavlennykh acid, dried and evaporated. The residue was subjected to flash-chromatography /silica, dichloromethane:methanol 50:1/. The appropriate fractions were collected and evaporated. The residue was recrystallized from ether-hexane and was obtained 11.2 g /82%/ product 46 48oC.

Analysis of C14H23NO2/%/:

Calculated: C 70,85, H 9,77, N 5,90

Found: C 71,16, to 9.93 H, N 5,94

Example 84

Ethyl Erythro-2-acetamido-3-/3-1/-decyl/-5-isoxazolyl/-3 - hydroxypropionate /7.9 g/ in anhydrous tetrahydrofuran /100 ml, cooled to 0oC, was added triethylamine /4.5 g/ in the presence of nitrogen. The solution was left to warm to room temperature and then stirred for 16 hours. The solution is evaporated, and the residue was recrystallized twice from ethyl acetate-hexane and was obtained 10.3 g /64%/ product, so pl. 83 85oC.

Analysis of C20H34N2O5/%/:

Calculated: C 62,80, H 8,96, N 7,32

Found: C 62,87, H of 9.30, N 7,32

Example 85

Erythro-2-amino-1-[3-/1-decyl/-5-isoxazolyl]-1,3-propandiol

A solution of Erythro-N-[1-[5-/decyl/-3-isoxazolyl]-1,3-dihydroxy-2-propyl] ndimethylacetamide /of 9.30 g/, degassed 2n.solution of sodium hydroxide /200 ml, 95% ethanol /100 ml stirred 6 hours at 80oC. the Reaction mixture was concentrated, the residue was diluted with sodium bicarbonate solution, and was extracted with a mixture of chloroform and 2-propanol 4:1. The combined organic extracts were dried with anhydrous magnesium sulfate; filtered and the filtrate evaporated. The residue was subjected to flash-chromatography /silica, dichloromethane:methanol 9: 1/. The appropriate fractions were collected and evaporated. The residue was recrystallized from ethyl acetate-hexane and received 6,1 g /75%/ product, so pl. 88 90oC.

Analysis of C16H30N2O3caldigit

A solution of 1-undecene /62,7 g/, 5-bromo-2 - thiophenecarboxaldehyde /75,0 g/ triethylamine /119,2 g/ in anhydrous tetrahydrofuran /300 ml/ degirolami and stirred at 0 to 5oC and under nitrogen atmosphere. Then was added 2M chloride bis/triphenylphosphine/palladium /5,51 g/ and after that 1 M of copper iodide /I/ /0.75 g/ and the mixture was degirolami and stirred for at room temperature and in the presence of nitrogen. The precipitate was filtered and the filter cake was washed with ethyl acetate. The filtrate is evaporated and the residue was purified flash chromatography /silica, 5% ethyl acetate-hexane/. The appropriate fractions were collected and evaporated in rezultatele received 88; 1 g /85%/ product in the form of an oily substance. This substance was dried at 50oC in high vacuum /approx. 0.01 mm RT.art./ within 4 hours and received analytical sample.

Analysis of C16H22OS /%/

Calculated: C 73,23, H 8,45

Found: C 73,15, H 8,50

Example 87

Ethyl Erythro-2-acetamido-3-[5-/1-undecenyl/-2-thienyl] -3 - hydroxypropionate

A suspension of 5-undecenyl-2-thiophenecarboxaldehyde /86,1 g/, complex monoethylene ether acetamidomalonate acid /62,0 g/, and anhydrous tetrahydrofuran (THF) /300 ml/ degirolami and was cooled to 0oC. Then was added triethylamine /is in 4 days. Then added 62,0 g complex monoethylene ether acetamidoacrylic acid and 34.8 g of triethylamine, and the reaction mixture was stirred two days at room temperature and under nitrogen atmosphere. After which the mixture is evaporated, and the residue was dried in vacuum. The residue was purified flash chromatography /silica; ethyl acetate: hexane 1:1/. The appropriate fractions were collected and evaporated, and the residue was recrystallized from ethyl acetate and resulted 86,5 g /65%/ product, so pl. 80 82oC.

Analysis of C22H33NO4S

Calculated: C 64,83, H 8,16, N 3,44

Found: C 64,65, H 8,07, N 3,45

Example 88

Erythro-N-[1-[5-/1-Undecenyl/-2-thienyl]-1,3-dihydroxy-2 - propyl]ndimethylacetamide

A solution of ethyl Erythro-2-acetamido-3-5-/1-undecenyl/-2-thienyl - 3-hydroxypropionate /86,2 g/ in anhydrous tetrahydrofuran /200 ml stirred at 0oC in the presence of nitrogen. Then one drop was added borohydride lithium /137,5 ml, 2.0 M in tetrahydrofuran/. The reaction mixture was left to warm to room temperature and then stirred for 4 hours in the presence of nitrogen. Then the mixture was cooled in an ice bath. Then was added a solution of methanol, water and acetic acid /50 ml: 50 ml: 10 ml/. The solution was neutralized glacial acetic acid. the extracts were dried with anhydrous sodium sulfate, was filtered, and the filtrate evaporated. The residue was purified flash chromatography /silicon dioxide, 7% methanol:dichloromethane/. The appropriate fractions were collected and evaporated. After recrystallization of the residue from ethyl acetate were received to 61.2 g /79%/ product, so pl. 88 90oC.

Analysis: C20H31NO3S

Calculated: C 65,72, H 8,55, N 3,83

Found: C of 66.00, H 8,71, N 3,82

Example 89

/4-TRANS/-N-[2,2-dimethyl-4-[5-/1-undecenyl/-2-thienyl]-1,3 - 5-yl]ndimethylacetamide

To a solution of Erythro-N-[1-[5-/1-undecenyl/-2-thienyl] -1,3 - dihydroxy-2-propyl/ndimethylacetamide/25 g/ in anhydrous acetone /400 ml) was added 2,2-dimethoxypropane /45,3 g/ and a catalytic amount of para-toluensulfonate acid. The solution is stirred at room temperature for 7 hours and then evaporated. The residue was purified column chromatography /silica gel, chloroform:ether 4:1./ The appropriate fractions were collected and concentrated. After recrystallization from ether-hexane got to 20.9 g /73,8%/ product, so pl. 88 89oC.

Analysis of C23H35NO3S

Calculated: C 68,11, H to 8.70, N 3,45

Found: C 68,26, H 8,83, N 3,39

Example 90

Erythro-N-[1-[5-/1-nominal/-2-thienyl]-1,3-dihydroxy-2 - propyl]-1,1-dimethylthiocarbamate

To a suspension of Erythro-2-amino-1-[5-/1-nominal/2-thienyl] -1,3- /2.24 g/ chloroform /50 ml for 2 minutes. The mixture is stirred 45 minutes at 60oC, then the layers were separated, and the organic layer was dried and evaporated. The residue was purified by passing it through a narrow strip of silica gel and the filtrate evaporated. The residue was led from ether-hexane and was obtained 2.9 g /77,6%/ product, so pl. 73 75oC.

Analysis of C21H33NO4S /%/:

Calculated: C 63,77, H to 8.41, N 3,54

Found: C 63,65, H 8,31, N 3,50

Example 91

Erythro-2-amino-1-[5-/1-nonyl/-2-thienyl]-1,3-propane diol acetate

A solution of Erythro-N-[1-[5-/1-nonyl/-2-thienyl] -1,3-dihydroxy-2 - propyl] ndimethylacetamide /7.30 g/ 2n solution of sodium hydroxide /100 ml 95% ethanol /75 ml stirred at 65oC during the night. Then the reaction mixture was concentrated and the aqueous residue was neutralized glacial acetic acid. The solution was diluted with water to 200 ml and was extracted with a mixture of chloroform and isopropanol /4: 1/. The combined organic extracts were dried with anhydrous sodium sulfate, filtered, and the filtrate evaporated. The residue was purified flash chromatography /silica; dichloromethane:methanol:ammonium hydroxide 90:9:1/. The appropriate fractions were collected and concentrated. The residue was dissolved in ethanol and added to an excess of glacial acetic acid. Then add simple isC.

Analysis of C18H33NO4S /%/:

Calculated: C 60,13, H a 9.25, N 3,90

Found: C 60,02, H 8,99, N 3,90

Example 92

Erythro-2-Dimethylamino-2-[5-/6-phenyl-1-hexenyl/-2-thienyl] 1,3-propandiol

To a mixture of Erythro-2-amino-1-[5-/6-phenyl-1-hexenyl/-2-thienyl]- 1,3-propane diol /4.0 g/, 37% aqueous formaldehyde /9,1/ ml and acetonitrile /50 ml) was added three partiallysighted sodium /to 2.29 g/, while stirring at room temperature. After stirring for 30 minutes, one drop was added glacial acetic acid /1 ml and continued to stir for another 30 minutes. The mixture is then neutralized with acetic acid and evaporated. To the residue was added 1N sodium hydroxide /200 ml, and the mixture was extracted with chloroform. The extracts were dried with anhydrous sodium sulfate, filtered, and the filtrate evaporated. The residue was subjected to flash chromatography on silica gel, elwira 10% methanol: dichloromethane. The appropriate fractions were collected and evaporated, resulting in a received 1.3 g /30%/ product in the form of butter.

Example 93

4-/1-dodecenyl/-2-thiophenecarboxaldehyde

A solution of 1-dodecyn /50,0 g/, anti-hydride /109,4 g/ and azobisisobutyronitrile /100 ml stirred 3 hours at 95oC. the Reaction mixture was cooled to 50

To a solution of 4-bromo-2-thiophenecarboxaldehyde /35,0/, tetrakis/triphenylphosphine/palladium /0/ /4,23 g/, 2,6-di-t-butyl-4 - METHYLPHENOL /a few milligrams/ dry toluene /150 ml/ drop) was added tri-n-butyl-1-dodecanesian /92.0/ at room temperature and in the presence of nitrogen. The solution was heated in a vessel under reflux for 4 hours, while stirring. After cooling to room temperature,the solution was filtered through a pad of celite, and the filter cake was washed simple ether. The filtrate is evaporated and the residue was purified flash chromatography /silica, 5% ethyl acetate-hexane/. The appropriate fractions were collected and concentrated. The residue was distilled in a ball furnace /170oC/0.3 mm RT.art./ and got to 46.7 g /92% / product in the form of oily substances /OK 4:1 TRANS: CIS/.

Analysis of C17H26OS /%/:

Calculated: C 73,33, H 9,41

Found: C 73,64, H 9,62

Example 94

Ethyl Erythro-2-acetamido-3-[5-/1-dodecenyl/-2-thienyl]-3 - hydroxypropionate

A suspension of 5-dodecyl-2-thiophenecarboxaldehyde /46,0 g, about 4:1 TRANS: CIS/, complex monoethylene ether acetamidomalonate acid /31,3 g/, and anhydrous then it is carbonated and, and the reaction mixture is stirred 3 days at room temperature in the presence of nitrogen. Then added a complex monotropy ether of acetamidomalonate acid /46,0 g/ and triethylamine /17,6 g/ and the reaction mixture stirred at room temperature and in the presence of nitrogen for three days. Then the reaction mixture was concentrated, and the residue was dried in vacuum. Then the residue was purified flash chromatography /silicon dioxide ethyl acetate:hexane 2:3/. The appropriate fractions were collected and concentrated.The residue was recrystallized from diethyl ether and was obtained 36 g /53%/ product /OK 4:1 TRANS:CIS/, so pl. 66 68oC.

Analysis of C23H37NO4S /%/:

Calculated: C 65,21, H 8,80, N 3,31

Found: C 65,36, H 8,71, N 3,32

Example 95

Erythro-N-{1,3-deacetylase-1-[6-/5-phenyl-1-pentyl/-2 - pyridinyl]-2-propanyl}ndimethylacetamide

Diastereometric a mixture of N-{ 1,3-dihydroxy-1-[6-/5-phenyl - 1-pentenyl/-2-pyridinyl] -2-propanyl}ndimethylacetamide /18,4 g, 6:1 Erythro:threo/, acetic anhydride /31,9 g/, triethylamine /47,5 g/, and 4-dimethylaminopyridine /0.64 g/ tetrahydrofuran /200 ml/ stirred over night at room temperature. The reaction mixture was concentrated, added methanol, and the mixture was heated at 50oC for 20 minutes. P sodium to obtain a pH of 8.5 and the mixture was extracted into chloroform. The extract was dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The residue was combined with one of the residues from analogous reactions /8.0 g, 18,8 mm/ and purified flash chromatography, elwira mixture of hexane and ethyl acetate 1:1. The appropriate fractions were collected and concentrated, resulting in received of 5.06 g /16,3%/ product, so pl. 104 106oC.

Analysis: C25H28N2O5/%/:

Calculated: C 68,79, H 6,47, N 6.42 PER

Found: C 68,69, H 6,47, N 6,36.

Example 96

Erythro-2-amino-1-[6-/5-phenyl-1-pentenyl/-2-pyridinyl] -1,3 - propane diol hemihydrate

Erythro-N-{1,3-dihydroxy-1-[6-/5-phenyl-1-pentenyl/-2 - pyridinyl/-2-propanyl}ndimethylacetamide /4.4 g/ 2n solution hydroxide /100 ml and ethanol /50 ml/ was heated at 60oC in the presence of nitrogen for 13 hours. Then the reaction mixture was cooled, extracted with chloroform, and the extract was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate evaporated. The residue was twice chromatographically on silica gel, elwira mixture of chloroform, methanol and 2n sodium hydroxide/950: 50: 3 920:80:5/. The appropriate fractions were collected and concentrated. The residue was dissolved in ethyl acetate, and the solution was washed nasishena which was obtained 1.13 g /36,5%/ product in the form of oily substances /dried at 60oC in vacuum/.

Analysis of C12H22N2O20.5 H2O /%/:

Calculated: C 71,44, H 7,26, N 8,77

Found: C 71,87, H 7,11, N 8,67.

Example 97

Erythro-N-[1,3-dihydroxy-1-/6-undecyl-2-pyridinyl/-2 - propenyl]ndimethylacetamide

A mixture of Erythro-N-{ 1,3-dihydroiso-1-[6-/1-undecenyl/-2 - pyridinyl] -2-propanyl} ndimethylacetamide /5,4 g/ in ethanol /125 ml) and 5% palladium charcoal /0.20 g/ hydrogenosomal in hydrogenator Parra at hydrogen pressure of 40 pounds per square inch /275,76 kPa/. After 2.5 hours, the catalyst was filtered, and the filtrate was concentrated. After recrystallization from ethyl acetate received a 4.9 /88,7%/ product, so pl. 97 to 98.5oC.

Analysis of C21H36N2O3/%/:

Calculated: C 69,19, H 9,95, N 7,68

Found: C 69,19, to 9.91 H, N OF 7.64

Example 98

Erythro-2-amino-1-/6-undecyl-2-pyridinyl/-1,3-propandiol

Erythro-N-[1,3-dihydroxy-1-/6-undecyl-2-pyridinyl/-2 - propenyl]ndimethylacetamide /and 3.72 g/, hydrazinehydrate /32 ml) and ethanol /25 ml/ was heated in a vessel under reflux in the presence of nitrogen within 24 hours. Then the reaction mixture was cooled, added water, and the resulting mixture was extracted with chloroform. The extract was washed with a saturated solution of sodium chloride, dried with anhydrous magnesium sulfate, filtrowa: 50: 3/. The appropriate fractions were collected and evaporated. The residue was dissolved in chloroform, the solution premillenarianism solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated, resulting in a received 1.45 g /44%/ product, so pl. 56 59oC /drained while 55oC in vacuum/.

Analysis of C19H34N2O2/%/:

Calculated: C 70,76, H 10,63, N 8,69

Found: C 70,20, H 10,71, N 8,48

Example 99

Erythro-2-amino-1-[6-/1-undecenyl/-2-pyridinyl] -1,3 - propane diol hemihydrate

Erythro-N-{1,3-dihydroxy-1-[6-/1-undecenyl/-2-pyridinyl]-2 - propanyl}ndimethylacetamide /5,4 g/ 2n sodium hydroxide /53 ml/ ethanol /35 ml/ was heated for 19 hours at 60oC in the presence of nitrogen. Then the reaction mixture was cooled, extracted with chloroform, and the extract was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was twice chromatographically on silica gel /chloroform: methanol: 2n. the ammonium hydroxide 950:50:3 930:70:5/. The appropriate fractions were collected, concentrated and received totaling 3.04 g /63,6% of the product in the form of oily substances /dried at 60oC in vacuum/.

Analysis of C19H30N2O25H
Diastereometric a mixture of N-{1,3-dihydroxy-1-[6-/1 - undecenyl/-2-pyridinyl] -2-propanyl} ndimethylacetamide /12.0 g, Erythro threo 4:1/, acetic anhydride /20,4 g/, triethylamine /30,4 g/ and 4-dimethylaminopyridine /0,41 g/ tetrahydrofuran /125 ml/ stirred over night at room temperature. Then the reaction mixture is evaporated, was added methanol, and the solution was heated for 20 minutes at 50oC, and then evaporated. Then added 7.5% sodium bicarbonate solution to obtain a pH of 8.5, and the mixture was extracted into chloroform. The extract was dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was purified flash chromatography, elwira with a mixture of hexane and ethyl acetate /1:1/. The appropriate fractions were combined, concentrated and received 3.5 g /24%/ product, so pl. 69 71oC.

Analysis of C25H36N2O5/%/:

Calculated: C 67,54, H 8,16, N 6,30

Found: C 67,65, H 8,23, N 6,18

Example 101

3-/1-Undecenyl/benzaldehyde

A mixture of 3-bromobenzaldehyde /51.8 g/ 1-undecene /48.6 g/ bis/triphenylphosphine/palladium (II) chloride /3,37 g/, iodide copper /457 mg/ triethylamine /196/ ml in anhydrous tetrahydrofuran /300 ml stirred 4 hours at 55oC. Then reactionuses was filtered, the filtrate was diluted whom Agnes, was filtered, and the filtrate was concentrated in vacuum. The residue was chromatographically on 300 g of silica gel /ethyl acetate: hexane 1:4/. The appropriate fractions were collected and evaporated. After distillation of 40 g of the sample residue /81.3 g/ received 9.5 g /13%/ product, so Kip. 172 174oC /0.5 mm RT.V./.

Analysis of C18H24O /%/:

Calculated: C 84,32, H 9,44

Found: C 84,76, H to 9.57

Example 102

Erythro-2-amino-1-/3-undecanoyl/-1,3-propane diol acetate

A solution of Erythro-N-{1,3-deacetylase-1-[3-/undecanoyl]-2 - propanyl}ndimethylacetamide /2.76 g/ and 2n aqueous solution of sodium hydroxide /62 ml/ ethanol /20 ml/ was heated to 60oC for 16 hours. Then the reaction mixture was cooled to room temperature and was extracted with chloroform. The extract was dried with anhydrous magnesium sulfate, filtered and the filtrate was concentrated in vacuum. The residue was chromatographically on silica gel /chloroform:methanol:ammonium hydroxide 900:100:5/. The residue was again chromatographically /chloroform:methanol 9:1/ received 1.35 g /71%/ free base.

To a solution of free base /1,05 g/ in dichloromethane /10 ml) was added glacial acetic acid /2 ml/ Stephenson /50 ml/. The resulting mixture was concentrated in vacuo and the solid residue of the processing> Analysis of C22H35NO4/%/

Calculated: C 69,99, H 9,34, N 3,71

Found: C 70,36, to 9.32 H, N 3,69

Example 103

Erythro-2-amino-1-[3-/1-iodizing/phenyl]-1,3-propane diol acetate

Erythro-N-{ 1,3-dihydroxy-1-[3-/1-dodecenyl/-phenyl]-2 - propanyl}ndimethylacetamide /2.7 g/ 2n solution of sodium hydroxide /36 ml/ ethanol /20 ml/ was heated at 60oC and in the presence of nitrogen for 19 hours. The reaction mixture was cooled and was extracted with chloroform. The extract was washed polysystem solution of sodium chloride, dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was chromatographically on silica gel, elwira a mixture of chloroform, methanol and 2n ammonium hydroxide /950:50:3/. The appropriate fractions were collected and evaporated. The residue was dissolved in dichloromethane and treated with glacial acetic acid /0,27 ml/. The mixture was concentrated in vacuum and the solid residue was recrystallized from ethyl acetate, resulting in a received 1,72 g /61%/ product, so pl. 104 105,6oC.

Analysis of C23H37NO4/%/:

Calculated: C 70,55, H 9,52, N TO 3.58

Found: C, 70.62 per, H 9,46, N 3,54

Example 104

Erythro-2-amino-1-[4-(1-dodecenyl)-2-thiazolyl]-1,3 - propeciageneric

A solution of Erythro-N-{1-[4-(1-dodecenyl)-2-thiazolyl]oC in a nitrogen atmosphere for 23 hours, the Reaction mixture was cooled, added water, and the mixture was extracted with chloroform. The extracts were washed with saline, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was subjected to chromatography on silica gel with elution with a mixture of chloroform, methanol and 2n. the sodium hydroxide solution taken in the ratio of 950:50:3. The appropriate fractions were collected and concentrated. Part of the balance in the amount of 2.4 g (the weight of the entire residue was 4.3 g) was dissolved in ethyl acetate, was added concentrated hydrochloric acid (0.6 ml) and the mixture was evaporated. The residue was again dissolved and evaporated together with ethyl acetate, and then C2-propane. The residue was dried under vacuum, resulting in a 2.4 g (yield 76,0%) of product; melting point was 194 197oC.

The results of the analysis:

calculated for C18H30N2SHCl: C 57,66% H - 6,33% N 7,47%

found: C 57,35% H 8,48% N 7,25%

Example 105

Acelerado-2-acetamido-3-[4-(1-dodecenyl)-2-thiazolyl] -3-hydroxypropionate

A solution of 4-(1-dodecenyl)-2-thiazolecarboxamide (18,3 g), inatalling of ester acetamidomalonate acid (14.1 g) and triethylamine (8,3 g) in dry tetrahedronal and recrystallized from ethyl acetate, resulting received 16.0 g (yield 57,0% ) of product, melting point was 131-132,5oC.

The results of the analysis:

calculated for C22H34N2O4S. C-62,53% H-8,11% N-6,63%

C-62,36% H-8,28% N-6.58 PERCENT

Example 106

Erythro-N-{ 1-[4-(1-dodecenyl)-2-thiazolyl] -1,3-dihydroxy-2-propanyl} ndimethylacetamide

To a solution of acelerado-2-acetamido-3-[4-(1-dodecenyl)-2-thiazolyl] -3-hydroxypropionate (13.8 g) in dry tetrahydrofuran (275 ml) was slowly added 2 M solution of lithium borohydride in tetrahydrofuran (14 ml), 5oC in a nitrogen atmosphere, and the mixture was stirred at room temperature for a time duration from Saturday until Monday. The reaction mixture was cooled and slowly added a mixture of methanol with water, taken in the ratio 1: 1, after which was added glacial acetic acid (1.8 ml) in a mixture (25 ml) of methanol with water, taken in the ratio 1:1. The solution was stirred at room temperature for 1 h, evaporated and then with methanol, was turned into an azeotrope. To the residue was added ethyl acetate, was added a saturated solution of sodium bicarbonate, bringing the pH to 8 and the mixture was extracted with ethyl acetate. The extract was washed with saline, dried over anhydrous Sullivan the ethyl acetate in the transition to a mixture of ethyl acetate with methanol (0.5 percent). Appropriate fractions were collected and evaporated. Part of the balance (the total weight of the residue was 11.1 g) in an amount of 8.0 g was recrystallized from ethyl acetate, resulting in received of 6.90 g (yield of 77.0%) of product, melting point was 93-95oC.

The results of the analysis:

calculated for C20H32N2O3S: C-63,12% H-8,48% N WAS 7.36%

found: C-63,26% H-8,82% N-7,30%

Example 107

Erythro-2-amino-1-[4-(1-dodecenyl)-2-thiazolyl]-1,3-propandiol

Erythro-N-{ -[4-1-(1-dodecenyl)-2-thiazolyl] -1,3-dihydroxy-2-propanyl} ndimethylacetamide (5.8 g), 39 ml of 2 n sodium hydroxide solution and ethanol was heated at 60oC in a nitrogen atmosphere for 23 hours, the Reaction mixture was cooled, added water, and the mixture was extracted with chloroform. The extract was washed with saline, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated. The residue was subjected to chromatography on silica gel with elution by chloroform. Appropriate fractions were collected and evaporated. Part of the balance in the amount of 1.9 g (from the total value of 4.3 g) was recrystallized from ethyl acetate, which was obtained 1.6 g (yield 71,0%) of product, melting point was 110-112oC.

The results of the analysis:

designed for having yl)-2-thiazolecarboxamide

A solution of 4-bromo-2-thiazolecarboxamide (14.8 g), 1-dodecyne (14.1 g) and triethylamine (23,5 g) in dry tetrahydrofuran (85 ml) was cooled to 5oC and obessively in a nitrogen atmosphere. To the mixture was added bis(triphenylphosphorane (11) chloride (0.54 g) and copper iodide (1) (0.07 g), then obessively and stirred in a nitrogen atmosphere at room temperature for 2.5 hours, the Reaction mixture was heated at 40oC for 7 h, and during this time has added additional quantity of 1-dodecene (3,9 g) chloride bis(triphenylphosphine)palladium(11) (0.11 g) and copper iodide(N) (0.02 g). The mixture was cooled to room temperature, the precipitate was collected, and the filter cake was washed with ethyl acetate. The filtrate was diluted with ethyl acetate (300 mg). Water was added in portions, and the organic layer was washed with saline, dried over magnesium sulfate, filtered, and the filtrate was concentrated. The residue was subjected to chromatography on silica gel, elwira heptane with the transition to a mixture of heptane to ethyl acetate (1% ). Part of the remainder (of 1.05 g) was re-subjected to chromatography elwira with a mixture of hexane with atidaryta (with the transition from 0.3% to 1% final solution). Appropriate fractions were collected and evaporated, resulting in a received 0,79 g (yield of 76.5%) of product, temperature-69,27% H-at 8.36% N-OF 5.05%

found: C-69,51% H-8,65% N-4,94%

1. 1-Alkyl, 1-alkenyl or 1-alkynylaryl-2-amino-1,3-propandiol General formula I

< / BR>
where R is

< / BR>
< / BR>
R5CH3(CH2)mCC-,

CH3(CH2)mCH-CH-CH3(CH2)mCH2CH2-,

< / BR>
< / BR>
< / BR>
m 3 15;

n 0 12;

R5dodecenyl;

R1hydrogen or

< / BR>
where R6hydrogen, lower alkyl, lower alkoxy or

< / BR>
R2hydrogen or lower alkyl;

R3hydrogen, lower alkyl or

< / BR>
where R6has the specified values;

R4-

< / BR>
where R7hydrogen, lower alkyl or CH2OR8where R8hydrogen or

< / BR>
where R6has the specified values;

R1and R8taken together with the oxygen atom to which they are attached, form a group of the formula

< / BR>
where R9and R10independently hydrogen or alkyl,

or their optical isomers, or pharmaceutically acceptable salt.

2. A method of obtaining a 1-alkyl-, 1-alkenyl - or 1-alkynylaryl-2-amino-1,3-propandiol General formula I on p. 1, characterized in that a) a compound of the formula

< / BR>
where R11-

< / BR>
< / BR>
R11and R1<CCH

or

< / BR>
where m and n have the specified values,

in order to obtain the compounds of formula I, where R has the above meaning, R5the group CH3(CH2)mCC or

< / BR>
R1and R2hydrogen;

R3the group COR6where R6lower alkyl;

R4group CO2R7where R7lower alkyl,

with or subsequent allocation of the target product, or b) not necessarily recover borhydride alkali metal in order to obtain the compounds of formula I, where R has the above meaning, R5-

-CH3(CH2)mCC-

or

< / BR>
R2hydrogen, R3the group COR6where R6is lower alkyl, R4the group CH2OH, or C) the optional hydrogenation of the compounds of formula I, obtained in stage a) or b) in order to obtain the compounds of formula I, where R has the above meaning, R5CH3(CH2)mCH2-CH2or

< / BR>
R1and R2hydrogen, R3COR6where R6- lower alkyl, and R4CO2R7where R7lower alkyl, or R4CH2OH, or d)optionally recovering the compounds of formula I, where R has the above meaning, R5- CH3(CHlower alkyl, and R4CO2R7where R7lower alkyl, with the use of alkaline borohydride in order to obtain the compounds of formula I, where R, R5, R1and R2have the specified values, and R4CH2OH, or (e) the optional hydrogenation of the compounds of formula I, where R has the above meaning, R5-CH3(CH2)mCC

or

< / BR>
R1and R2hydrogen, R3COR6where R6- lower alkyl, and R4CH2OH, in order to obtain the compounds of formula I, where R, R1, R2, R3and R4have the above meanings and R5CH3(CH2)mCH CH or

< / BR>
or f) optional hydrolysis of the compounds of formula I, where R has the above meaning, R1and R2hydrogen, R3COR6where R6lower alkyl, and R4CH2OH, in order to obtain the compounds of formula I, where R, R5, R1, R2and R4have the specified values, R3hydrogen, or (g) optional interaction of the compounds of formula I, where R has the above meaning, R1, R2and R3the hydrogen and R4CH2OH, with a lower aldehyde in the presence of a reducing agent in order to obtain the compounds of formula I, where R and R5and R3sory interaction of the compounds of formula I, where R has the above meaning, R1, R2and R3the hydrogen and R4< / BR>
-CH2OH with N-benzyloxycarbonyloxy-succinimido formula

< / BR>
in order to obtain the compounds of formula I, where R and R5have the specified values, R1and R3benzyloxycarbonyl, R2the hydrogen and R4CH2OR8where R8benzyloxycarbonyl, or the optional acylation of the compounds of formula I, where R have the above values, R1and R2hydrogen, R3COR6where R6lower alkyl, and R4CH2OH, in order to obtain the compounds of formula I, where R, R5, R1, R2and R3have the specified values, and R4CH2OCOR6where R6- lower alkyl, or l) optional interaction of the compounds of formula I, where R has the above meaning, R1and R2hydrogen, R3- COR6where R6lower alkyl, and R4CH2OH, 2,2-dimethoxy-propane, in order to obtain the compounds of formula I, where R, R2and R3have the specified values, R4- CH2OR8and R1and R3taken together form a group of the formula

$

 

Same patents:

The invention relates to the field of organic chemistry, namely the chemistry of azo compounds which are used as acid-base indicators

The invention relates to 1-alkyl, 1-alkenyl or 1-alkynylaryl-2-amino-1,3-propandiol formula I

RCH (OR1)CHN(R2R3)P4whereOSO

R5-CH3(CH2)mCC,

CH3(CH2)mCH=CH-, CH3(CH2)mCH2-CH2-,-CH2(CH2)nCC-,

-CH2(CH2)nCH= CH or-CH2(CH2)nCH2-CH2-, where m = 3-15; n = 0-12;

R1is hydrogen orR6where R6is hydrogen, alkyl, alkoxy, or OCH2-;

R2is hydrogen or alkyl;

R3is hydrogen, alkyl orOR7where R7is hydrogen or alkyl, or CH2OR8where R8is hydrogen orR6where R6is defined above,

R1and R8taken together with the oxygen atom to which they are attached, form a group of the formula

where R9and R10independently are hydrogen or alkyl

The invention relates to 1-alkyl, 1-alkenyl or 1-alkynylaryl-2-amino-1,3-propandiol formula I

RCH (OR1)CHN(R2R3)P4whereOSO

R5-CH3(CH2)mCC,

CH3(CH2)mCH=CH-, CH3(CH2)mCH2-CH2-,-CH2(CH2)nCC-,

-CH2(CH2)nCH= CH or-CH2(CH2)nCH2-CH2-, where m = 3-15; n = 0-12;

R1is hydrogen orR6where R6is hydrogen, alkyl, alkoxy, or OCH2-;

R2is hydrogen or alkyl;

R3is hydrogen, alkyl orOR7where R7is hydrogen or alkyl, or CH2OR8where R8is hydrogen orR6where R6is defined above,

R1and R8taken together with the oxygen atom to which they are attached, form a group of the formula

where R9and R10independently are hydrogen or alkyl

The invention relates to methods for isoxazolone derivatives of General formula I

where R1is a hydrogen atom, a halogen atom or an alkyl group containing 1-6 carbon atoms;

R2is a hydrogen atom; an alkyl group containing 1-4 carbon atoms; phenyl group which is unsubstituted or which is substituted by at least one of substituents (a), defined below; or a heterocyclic group, which contains 5 or 6 ring atoms, of which 1 is a nitrogen atom or sulfur heteroatom;

R1and R2together form a group of the formula

-CR4=CR5-CR6=CR7- , in which R4, R5, R6and R7the same or different and each expresses: a hydrogen atom; a halogen atom, alkylene containing 1-4 carbon atoms; alkoxy group containing from 1 to 4 carbon atoms;

R3- piperidyl, substituted piperidyl, in which the nitrogen atom is substituted by an alkyl group containing 1-6 carbon atoms, or hinokitiol, the substituents (a) halogen atoms, alkoxygroup containing 1-4 carbon atoms; hydroxy-group, which can be used in the treatment and prevention of various disorders, OS
The invention relates to chemical pharmaceuticals, namely the method of obtaining diacetate 2-pyridyl-4,4-biphenylene (1) known drug of Bisacodyl used in medical practice as a laxative [1]

A method of obtaining (1) by condensation of derivatives of pyridine-2-carboxylic aldehyde, for example azina, oxime, semicarbazone, etc

The invention relates to 1-alkyl, 1-alkenyl or 1-alkynylaryl-2-amino-1,3-propandiol formula I

RCH (OR1)CHN(R2R3)P4whereOSO

R5-CH3(CH2)mCC,

CH3(CH2)mCH=CH-, CH3(CH2)mCH2-CH2-,-CH2(CH2)nCC-,

-CH2(CH2)nCH= CH or-CH2(CH2)nCH2-CH2-, where m = 3-15; n = 0-12;

R1is hydrogen orR6where R6is hydrogen, alkyl, alkoxy, or OCH2-;

R2is hydrogen or alkyl;

R3is hydrogen, alkyl orOR7where R7is hydrogen or alkyl, or CH2OR8where R8is hydrogen orR6where R6is defined above,

R1and R8taken together with the oxygen atom to which they are attached, form a group of the formula

where R9and R10independently are hydrogen or alkyl

FIELD: organic synthesis.

SUBSTANCE: 1-(2-pyridyl)-1,2-ethandiol finding use as starting compound in synthesis of therapeutical preparations (ethoxadrol, dexoxadrol, laevoxadrol, and dioxadrol) and as a component in synthesis of polyester polymers is prepared via interaction of equimolar amounts of 2-vinylpyridine and 5% potassium permanganate aqueous solution in water/acetone mixture (3:2 by volume) followed by neutralization of reaction mixture with sulfuric acid in presence of isopropyl alcohol and isolation of desired product.

EFFECT: increased yield and purity of product.

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):

and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:

wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

22 cl, 1 tbl, 2 sch, 78 ex

FIELD: organic chemistry, chemical technology, medicine, endocrinology.

SUBSTANCE: invention relates to a method for preparing an antidiabetic agent pioglitazone of the formula (I): . Method involves condensation of 4-substituted phenol or phenolate of the general formula (II): wherein R represents organic radical comprising amino-group and chosen from group comprising group of the general formula: -NHRa (IIa) wherein Ra means hydrogen atom or protective group that is removed before the following treatment, and group of the general formula: wherein Rb represents carboxyl group as free acid or as salt or ester; M represents hydrogen atom or alkaline metal with pyridine base of the general formula (III): wherein Z means a removing group distinguishing from halogen atom and wherein the following steps are carried out: (a) diazotization reaction of amino-group as a moiety of organic radical R; (b) conversion of diazotized radical R to derivative of 2-halogenpropionate or 2-halogenpropionitrile of the formula: wherein Rb is determined above; X represents halogen atom; (c) cyclization of derivative of 2-halogenpropionate or 2-halogenpropionitrile with thiourea, and (d) hydrolysis of imine prepared. In case when R represents group of the formula (IIa) method involves firstly carrying out the condensation reaction followed by carrying out steps (a)-(d) to obtain agent of the formula (I); or in case when R represents group of the formula (IIb) then method involves firstly carrying out steps (a)-(d) followed by condensation with pyridine base of the general formula (III) to obtain agent of the formula (I). Also, invention describes compounds of the formula (V): wherein Ra represents a protective group chosen from group comprising acyl, n-alkoxycarbonyl, tert.-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, allyloxycarbonyl, 2-cyanoethoxycarbonyl as an intermediate substance in synthesis of compound of the formula (I).

EFFECT: improved preparing method of agent.

12 cl, 5 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 1-[1-hydroxy-1-(pyrid-4-yl)methyl]-1,2-dihydro[60]fullerene. Method involves interaction of C60 with ethylaluminum dichloride and magnesium in the presence of catalyst, in argon atmosphere, at room temperature and under atmosphere pressure in medium of mixed solvent tetrahydrofuran-toluene for 8 h followed by addition nickel-containing catalyst and 4-pyridinecarbaldehyde to the reaction mass at -15°C. Then the reaction mass is stirred at room temperature for 6-10 h followed by its hydrolysis. The total yield of end substances after hydrolysis of the reaction mass is 33-52%. Invention provides the development of a method for synthesis of novel fullerene-containing alcohols. Synthesized compound can be used in fine organic synthesis, manufacture of drugs and biologically active substances.

EFFECT: improved method of synthesis.

1 tbl, 1 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 1-[3-hydroxy-3-(pyrid-4-yl)prop-1-yl]-1,2-dihydro[60]fullerene. Method involves interaction of C60 with triethylaluminum in the presence of catalyst, in argon atmosphere, at room temperature and under atmosphere pressure, in toluene medium for 8 h followed by addition of nickel-containing catalyst and 4-pyridinecarbaldehyde at temperature -15°C followed by stirring the reaction mass at room temperature for 6-10 h and the following hydrolysis. The total yield of end substances after hydrolysis of the reaction mass is 48-69%. Proposed compounds can be used in fine organic synthesis, in manufacture of drugs and biologically active substances. Invention provides the development of method for synthesis of novel fullerene-containing alcohols.

EFFECT: improved method of synthesis.

1 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of aminoalkylpyridines of the general formula (I): wherein n means a whole number from 1 to 4; R1 represents hydrogen atom, hydroxyl group or lower (C1-C6)-alkoxy-group; R2 represents hydrogen atom or lower (C1-C6)-alkyl group with linear or branched chain; X represents hydrogen atom, fluorine atom, chlorine atom, bromine atom, hydroxyl group, trifluoromethyl group, 3,4-di-Cl, 2,4-di-Cl or lower (C1-C6)-alkoxy-group, or salts of these compounds as products of adding physiologically acceptable acid. Also, invention relates to a pharmaceutical composition based on these compounds inhibiting biosynthesis of cholesterol. Also, invention considers using abovementioned compounds in preparing pharmaceutical composition and to a method for synthesis of compounds of the formula (I). Invention provides synthesis of novel compounds possessing valuable biological properties and preparing pharmaceutical composition based on thereof.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical composition.

10 cl, 12 dwg, 5 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to 2-hetaryl-substituted derivatives of 1,2-tropolones of the general formula (Ia): wherein R1 and R2 mean (C1-C6)-alkyl; R3 means hydrogen atom, (C1-C6)-alkyl, nitro-group; Het means six-membered nitrogen heterocycle condensed with one or two benzyl rings that can be substituted with substitutes chosen from group comprising halogen atom, nitro-group, (C1-C6)-alkyl, oxy-(C1-C6)-alkyl, secondary amino-group chosen from anilino-, substituted anilino-, hydroxyethylamino-group, or tertiary amino-group chosen from morpholino-, piperidino-, piperazino-group, 1H-1-imidazolyl. Also, invention relates to a method for synthesis of 2-hetaryl-substituted derivatives of 1,3-tropolone. Method involves condensation of benzoquinones-1,2 with 2-methylheterocycles at heating in the presence of acetic acid taken in the amount providing its role as both a catalyst and a solvent. Also, invention relates to a pharmaceutical composition with antibacterial effect based on 2-hetaryl-substituted derivatives of 1,3-tropolone.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

9 cl, 5 tbl, 3 ex

FIELD: medicine; pharmacology.

SUBSTANCE: description is provided for the derivative of phenylalcan or phenyloxyalcan acids, formula (I), or their pharmaceutically acceptable salt or hydrolysable ester, where: R1 and R2 independently present the H or С1-3alkyl; X presents the O or (СН2)n where n is 0.1 or 2; R3 and R4 independently present the H, С1-3alkyl, -ОСН3, CF3, allyl or halogen; X1 presents О, S, SO2, SO or СН2; one of R5 and R6 independently presents hydrogen, and another - С1-6alkyl (including the ramified alkyl and, probably, the substituted С1-6alkoxy); R7 presents a phenyl or hexamerous heterocycle taken from pyridine, and each of specified phenyl or heterocycles is substituted by phenyl (probably, substituted by one ore more С1-3alkyl, CN, halogen or CF3). The pharmaceutical composition is also described.

EFFECT: compounds can be used in treatment of cardiovascular and endocrine diseases.

13 cl, 145 ex

FIELD: chemistry.

SUBSTANCE: invention refers to production method of α-racemate of 1-(2-piridyl)-1,2-ethandiol: catalytic reducing (1RS)-1-(2-piridyl)-1,2-ethandiol distinctive in that nickel aluminium alloy is used as catalyst, while reduced at atmospheric active hydrogen pressure generated by reaction (1RS)-1-(2-piridyl)-1,2-ethandiol with sodium hydroxide in aqueous medium, resulted in and β-racemates of 1-(2-piperidyl)-1,2-ethandiol and their subsequent diethyl ether fractional crystallisation to produce end product applied as raw product for medical product synthesis, such as Ethoxadrol, Dexoxadrol, Levoxadrol, Dioxadrol.

EFFECT: higher yield and purity of declared connection, as well as reduction of synthesis stages number.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: in novel substituted aryl ketones of formula (I) Z stands for groupings and A1, A2, A3, R1, R2, R3, R4, R5, R6, R7, X and Y and m are such as given in formula of invention. In substituted aryl carboxylic acid of formula (II) and derivative of aryl carboxylic acid of formula (III) A1, A2, A3, R1, R2, X and Y are such as given in item 1 of invention formula, R12 stands for allyl, which are intermediate products. Also described is means to fight undesirable plants based on formula (I) compound.

EFFECT: increased herbicidal activity.

7 cl, 3 tbl, 10 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes tritium labeled N-phenylquinolinium and quinaldinium salts of the general formula: wherein R means hydrogen atom (H), -CH3; X means BF-4, ClO-4, J-. Method involves ion-molecular reaction of quinoline or quinaldine (2-methylquinoline) with free tritium labeled phenyl cations that are generated spontaneously in beta-decay of tritium as components of tritium labeled benzene in a closed system in the presence of tetrafluoroborate, perchlorate or potassium iodide as a stabilizing salt. Novel substances can be used in biological and medicinal investigations.

EFFECT: improved method of synthesis.

2 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to N-phenyllepidine salts tritium labeled in the phenyl substitution group with the general formula: Moreover, the invention refers to the way of production of tritium labeled N-phenyllepidine salts.

EFFECT: new compounds that are characterized by antibacterial and antifungal action, and development of the way of their production.

2 cl, 1 dwg, 1 tbl, 2 ex

FIELD: biotechnologies.

SUBSTANCE: invention refers to new positively charged NSAIA prodrugs of a common formula (1, 2a, 2b, 2c or 2d) of "1, 2a, 2b, 2c or 2d structure"

Structure 1, Structure 2a,

Structure 2b, Structure 2c, Structure 2d. Values of R, R1, R2, R3, R4, R5, Ary, X radicals are presented in Claims 1,2.

EFFECT: increasing agent penetration speed.

22 cl, 14 tbl

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