The way to obtain 2,6-dimethyl-10-methylene-4 - c1- c4- alkoxycarbonyl-2,6,11-dodecatrien
The invention relates to organic chemistry, in particular, to a method for producing 2,6-dimethyl-10-methylene-4-C1-C4arcoxia - bonil-2,6,11-dodecatrien.The aim of the invention is to develop a method of producing 2,6-dimethyl-10-methylene-4-C1-C4-alkoxycarbonyl-2,6,11-dodecatrien - on, allowing for its use as intermediate compounds in the synthesis of vitamin E to receive the latter with a higher yield.The invention is illustrated by the following examples.The original 3-hlormaren get out of myrcene with access to 84.6% by well-known methods.P R I m e R 1. Into a flask of 100 ml is injected in the atmosphere of argon, 10 ml of dry pentane, 2,07 Diisopropylamine (20 mmol). After cooling to 0aboutWith add 12.5 ml of a solution of n-utility in hexane (1.6 M/l), which corresponds to 20 mmol. The reaction mixture is left for 20 min at 0aboutWith, after which it is cooled to -78aboutC. To the reaction mixture slowly add 2,78 g of ethyl ester of 4-methyl-3-pentenol acid (20 mmol), after which it is left for 20 min at -78aboutC and then for 1 hour at a temperature of about 20aboutC.In the second flask 100 ml injected into the atmosphere Argo is 5 g of 6-chloro-3-methylene-7-methyl-1,7-octadiene (20 mmol).With a needle for transfer of reagents into the second flask enter the carbanion obtained in the first flask, this operation takes 20 min, after which the reaction mixture is left for 2 hours at a temperature of about 20aboutC. the Color of the solution changed from light yellow to orange. The reaction mixture was poured into 30 ml of 10% hydrochloric acid. The aqueous phase is separated by decantation and extracted with ether. The organic phase is collected and dried over magnesium sulfate. After filtration and removal of the solvent receive 5,08 g butter yellow color. As the result of acceleration under reduced pressure (temperature 111-118aboutWith 1.4 mm RT.article; 0,18 kPa) to obtain 4.5 g of a mixture of products 1 and 2: 1) (CH3)2C= CH-CH(CO2C2H5)-CH2-C(CH3)= CH-CH2-C(= CH2)-CH= CH22) CH2= C(CH3)-CH-/CH(CO2C2H5)-CH= = C(CH3)2/-CH2-CH2-C(= CH2)-CH= CH2The output is of 81.5%. Analysis by chromatography in gas phase gives the ratio of the quantities = 98%.The structure of the resulting product is confirmed by IR spectra, mass spectra and spectra, proton nuclear magnetic resonance (PMR).Connection 1: mass spectrum: m/e = 276 (M+)
IR-spectrum (Planck CDCl3offset in parts per million)
m - a comprehensive array; S = singlet; d = doublet; t = triplet; q = keyrepeat; I = coupling constant in Hz.Connection 2: mass spectrum: m/e = 276 (M+)
range PMR (360 MHz, CDCl3offset in parts per million)
< / BR>P R I m m e R 2 illustrates the use of product 1 for the synthesis of vitamin E.a) In a three-neck flask of 100 ml equipped with a reflux condenser and a thermometer, is injected at a temperature of about 20aboutFrom 22.9 g of product combinations, obtained according to example 1, which corresponds to 87,4 the mmol, 0,0458 g /Ph Cl (1, 5cyclooctadiene)/(0,186 grammatim Ph), 0,0847 g Na2CO3(0.8 mmole), 1,110 land only g traintravel salt three(metasulfite)phosphine (TPPTSNa), 20 ml of ethanol-water (75-25 by volume) and 22,36 g methylacetoacetate (192 mmole). The reaction mixture is left at the 75aboutC for 24 hours, After cooling the solution to it was added 100 ml of ether. After desantirovaniya the organic phase is washed with three portions of 30 ml of water. The solvent is distilled off and remove the remaining mass of 100 ml of pentane. Then the organic phase is washed with three portions of 30 ml of water, combine the organic phase and dried over magnesium sulfate. After filtration and distillation of RA is(CO2CH3)-CH2-C(CH3)= = CH-CH2CH2-C(CH3)= CH-CH2-CH(CO2CH3)- -CO-CH3and (CH3)2C=CH-CH(CO2CH3)-CH2-C(CH3)= =CH-CH2-CH2-C(= CH2)-CH2-CH2- CH(CO2CH3)-CO-CH3The output is 93.7%.Mass spectrum: m/e = 378 (M+)
IR spectrum (film), cm-1: 1740 [C=0 (ester)], 1720 [CO (ketone)], 1645 (C=C), 1160 (C-O), and 895 (C=CH2; = CH)
range PMR (360 MHz, CDCl3the shift in parts per million).b) In the flask 100 ml injected 29,95 g of the product obtained according to example 2A (79,2 mmole), 31 g of the solution 30,75% of the hydroxide of sodium, which corresponds 0,238 mole of hydrate of sodium oxide and 60 ml of water. The reaction mixture is left for 1 hour at a temperature of 40aboutWith until a homogeneous yellow solution, after which there was added 7 ml of 95% sulfuric acid and 18 ml of water. The reaction mixture is again left for 1 hour at a temperature of 25aboutC. While there is plenty of carbon dioxide. The resulting solution was extracted with three portions of 30 ml of ether, the combined organic fractions and dried over magnesium sulfate. After filtration and distillation of the solvent to be obtained with a yield of 95% 23,19 g of a mixture of products is2- -CO-CH3(CH3)2C=CH-CH(CO2H)-CH2-C(CH3)= =CH-CH2CH2-C(=CH2)-CH2-CH2-CH2-CO-CH3< / BR>Mass spectrum: m/e = 306 (M1)
IR spectrum (film), cm-1: 1710 (C=O), 1600 (C=C), 895 (C=CH2) and 840 cm-1(C=CH)
range PMR (360 MHz, CDCl3offset in parts per million).< / BR>C) In an autoclave at 125 ml stainless steel is introduced into the argon atmosphere 5 g of the product obtained according to example 2B (16.3 mmole), 30 ml of pentane and 0.2 g of 10% palladium on charcoal, and then introducing hydrogen to a pressure 100 bar. The reaction mixture is left for 12 hours at a temperature of about 20aboutC. After filtration and removal of the solvent receive a colorless oil, containing 98% of the product of the formula: (CH3)2CH-CH2-CH(CO2H)-CH2-CH(CH3)- -CH2-CH2-CH2-CH(CH3)-CH2-CH2-CH2-
-CO-CH3< / BR>The structure of the obtained product is confirmed by mass spectra, IR spectra and spectra proton NMR and carbon (C13nuclear magnetic resonance.In the heat treatment of the obtained product at 150aboutTo get phyto is2-CH2-CH2-CO-CH3. Output 90%.The hydrogenation product before heat treatment:
mass spectrum: m/e = 312 (M+)
IR spectrum (film), cm-1: 1710 (C=O).The IR spectrum of Fiona identical IR spectrum described in the literature.d) Translation of Fiona in vitamin E-known method.Thus the proposed method allows to obtain 2,6-dimethyl-10-methylene-4-C1-C4-alkoxy-carbonyl-2,6,11-Daudet - sodium, the use of which as an intermediate product in the synthesis of vitamin E enables you to obtain the latest with a higher yield (54.1 per cent). THE WAY TO OBTAIN 2,6-DIMETHYL-10-METHYLENE-4 - C1-C4-ALKOXYCARBONYL-2,6,11-DODECATRIEN, characterized in that C1-C4-alkilany ether 4-methyl-3-pentenol acid is subjected to unionization butyllithium in the presence of Diisopropylamine obtaining anion of the formula
where R is C1- C4-alkyl,
which is subjected to interaction with 7-methyl-3-methylene-6-chloro-1,7-octadiene at 20 - 25oIn the presence of palladium catalyst, modified with triphenylphosphine in an environment aprotic solvent.
FIELD: organic chemistry, labeled compounds.
SUBSTANCE: invention relates to new tritium-labeled 2-arachidonoyl-[1,3-3H]-glycerol of the formula: CH3-(CH2)4-(CH=CHCH2)4-(CH2)2-COOCH-(C3HHOH)2 able to bind and activate cannabinoid receptors. This compound can be used in analytical, bioorganic chemistry, biochemistry and applied medicine.
EFFECT: valuable properties of compound.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to application of compounds with formula R2=R1-X, where R1 and R2 have 23 to 35 carbon atoms in sum, X represents primary alcohol functional group -CH2OH or carboxyl group -COOH, R1 is saturated linear hydrocarbon chain with 9 carbon atoms, and R2 is linear hydrocarbon chain, which is saturated or unsaturated, including 1 to 4 unsaturated double links.
EFFECT: producing formulations suited for application to hypercholesterolemia therapy and prophylaxis.
3 cl, 4 tbl, 6 ex
SUBSTANCE: invention refers to new compounds of formula (I) where X is carboxylic acid, carboxylates, carboxylic anhydride, diglyceride, triglyceride, phospholipid, or carboxamides, or to any their pharmaceutically acceptable salt. The invention particularly refers to (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)-ethyl 2-ethyldocosa-4,7,10,13,16,19-hexanoate. The invention also refers to a food lipid composition and to a composition for diabetes, for reducing insulin, blood glucose, plasma triglyceride, for dislipidemia, for reducing blood cholesterol, body weight and for peripheral insulin resistance, including such compounds. Besides, the invention refers to methods for treating and/or preventing diabetes, dislipidemia, peripheral insulin resistance, body weight reduction and/or weight gain prevention, insulin, blood cholesterol, blood glucose and/or plasma triglyceride reduction.
EFFECT: higher clinical effectiveness.
61 cl, 4 tbl, 16 dwg, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a new lipid compound of general formula , wherein n=0; R1 and R2 are identical or different, and may be specified in a group of substitutes consisting of a hydrogen atom, a C1-C7alkyl group, a halogen atom and a C1-C7alkoxy group; X represents COR3 or CH2OR4, wherein R3 is specified in a group consisting of hydrogen, hydroxy, C1-C7alkoxy and amino; and R4 is specified in a group consisting of hydrogen, C1-C7alkyl or C1-C7acyl, Y represents C9-C21 alkene with one or more double bonds in E- or Z-configurations with the chain Y being unsubstituted and containing a double bond in the ω-3 position; provided R1 and R2 cannot simultaneously represent a hydrogen atom.
EFFECT: invention refers to pharmaceutical compositions containing the lipid compounds which are used for treating and/or preventing the conditions related to high NFkB functions, treating and/or preventing an inflammatory disease or a condition, lower plasma insulin and/or blood glucose levels, treating insulin resistance, treating and/or preventing peripheral tissue insulin resistance and/or diabetic condition, eg type 2 diabetes mellitus.
45 cl, 1 tbl, 1 dwg, 31 ex
SUBSTANCE: invention relates to novel omega-3 lipid compounds of general formula (I) or to their pharmaceutically acceptable salt, where in formula (I): R1 and R2 are similar or different and can be selected from group of substitutes, consisting of hydrogen atom, hydroxy group, C1-C7alkyl group, halogen atom, C1-C7alkoxy group, C1-C7alkylthio group, C1-C7alkoxycarbonyl group, carboxy group, aminogroup and C1-C7alkylamino group; X represents carboxylic acid or its carbonate, selected from ethylcarboxylate, methylcarboxylate, n-propylcarboxylate, isopropylcarboxylate, n-butylcarboxylate, sec-butylcarboxylate or n-hexylcarboxylate, carboxylic acid in form of triglyceride, diglyceride, 1-monoglyceride or 2-monoglyceride, or carboxamide, selected from primary carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, N-ethylcarboxamide or N,N-diethylcarboxamide; and Y stands for C16-C22 alkene with two or more double bonds, which have E- and/or Z-configuration.
EFFECT: described are pharmaceutical and lipid compositions, which contain said compounds, for application as medications, in particular, for treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, for instance, type 2 diabetes, increased levels of triglycerides and/or levels of non-HDL cholesterol, LDL cholesterol and VLDL cholesterol, hyperlipidemic condition, for instance, hypertriglyceridemia (HTG), obesity or condition of excessive body weight, fatty liver disease, for instance, non-alcoholic fatty liver disease (NAFLD) or inflammatory disease or condition.
60 cl, 3 tbl, 65 ex
SUBSTANCE: invention relates to versions of a compound of formula where R1 is a hydrogen atom; R2 is a lower alkyl group; P is H; , where P1, P2 and P3 are identical or different and are selected from a hydrogen atom, a lower alkyl group and a C14-C22 alkenyl group substituted with a lower alkyl group; or where P1 is an alkenyl group, and each of P2 and P3 is a hydrogen atom; and Y is a C14-C22 alkenyl group with at least one double bond having a Z-configuration, and having a first double bond at the third carbon-carbon bond from the omega (ω)-end of the carbon chain, capable of lowering the level of triglycerides and cholesterol, a pharmaceutical or lipid composition based on the disclosed compounds, as well as use (versions) of the disclosed compounds.
EFFECT: high efficiency of using compounds.
32 cl, 6 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to compounds of the following formula , in which n equals integer number from 1 to 15, m equals 0, 1, 2 or 3, and R represents hydrocarbon chain of polyunsaturated fatty acid, selected from omega-3 and omega-6 polyunsaturated fatty acids, and to method of obtaining them.
EFFECT: development of pharmaceutical or cosmetic composition based on said compounds and to method of acne or seborrheic dermatitis treatment for cosmetic purposes.
16 cl, 4 dwg, 2 tbl, 3 ex
SUBSTANCE: ophthalmic composition contains a formula compound, where the values for R1 and R2 groups are given in the claims, and an ophthalmologically acceptable carrier. The invention also relates to a method for dry eye treatment, comprising local administration of a therapeutically effective amount of the ophthalmic composition to the eye of the subject in need.
EFFECT: increased efficiency.
20 cl, 6 dwg, 6 ex
SUBSTANCE: invention relates to the production method of ethyl(2E,4E)-5-chloropenta-2.4-dienoate. Ethyl(2E,4E)-5-chloropenta-2.4-dienoate is the prospective starting compound in the synthesis of (2E,4E)-dienoic acids and its derivatives. The results of the invention can be used in chemistry, fine organic synthesis and low-tonnage chemical industry. The production method of ethyl(2E,4E) -5-chloropenta-2.4-dienoate is based on the olefination of (2E)-3-chloroprop-2-enal, where the product is formed by the single-reactor oxidation of (2E)-3-chloroprop-2-en-1-ol with barium manganate (BaMnO4) to (2E)-3-chloroprop-2-enal, with further olefination of the latter (carbethoxymethylene) triphenylphosphorane in dichloromethane at the room temperature within 20 hours. The invention target is to provide more efficient, simple and safe process of production ethyl(2E,4E)-5-chloropenta-2.4-dienoate with higher yield.
EFFECT: higher product yield, efficiency, safety and procedure simplicity, due to the lack of need to use, produced with low-yield, uncomfortable and dangerous to handle pure compound.