Method for preparing xanthophyll

FIELD: organic chemistry of natural substances, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing xanthophylls, in particular, to a method for preparing mono- or polyoxidized xanthophylls. Method involves oxidation of carotinoid in a lower oxidation state as compared with xanthophylls to be prepared from hydrogen peroxide aqueous solution and organic solvent wherein indicated solvent represents a water-insoluble solvent. Indicated reaction is carried out in the presence of iodine-containing compound chosen from the group including iodine, iodine halide derivative and metal iodide. Method allows avoiding using danger and expensive substances and formation of large amounts of salts. The proposed invention is used mainly for oxidation of beta-carotene to form canthaxanthine and oxidation of lutein and zeaxanthine wherein the end substances represent important agents used in preparing food compositions and supplements in animal fodder.

EFFECT: improved method for preparing.

11 cl, 2 dwg, 2 ex

The technical field to which the invention relates.

The present invention relates to a method of producing xanthophyll and, mainly, to the method of producing xanthophyll by oxidation of carotene in the presence of hydrogen peroxide and iodine-containing compounds.

The level of technology

The xanthophylls are a special group of carotenoids. Carotenoids include hydrocarbons such as carotene and its oxygendemand alcohol derivatives, such as xanthophylls. Examples of carotenes can serve as alpha-carotene, beta-carotene and lycopene. Representatives of xanthophylls include lutein, zeaxanthin, capsorubin, capsanthin, astaxanthin and canthaxanthin. Carotenoids are important agents for molding food materials and additives in animal feed.

From US Patent 4212827 and European Patent Application EP 1059290 known ways of getting canthaxanthin, consisting in the oxidation of beta-carotene by sodium chlorate, sodium bromate, sodium Iodate, sodium perchlorate, meta-sodium perchlorate in the presence of such catalysts as iodine, bromine, selenium dioxide, vanadium pentoxide, niobium or osmium tetroxide.

In WO 99/26914 described obtaining astaxanthin from lutein or zeaxanthin. In such ways, there is no stage of oxidation.

In the above-mentioned methods of oxidative reagents, perchlorates, chlorates bromine and iodates of shelo the different metals are introduced into the reaction mixture in excess relative to the quantity required by stoichiometry. As a rule, theoretically required quantity are four equivalent. Moreover, these chemicals are very dangerous and expensive substances, and in the process formed a noticeable amount of salt that should be taken into account and implement appropriate treatment.

The invention

The authors of the present invention, it was found that the xanthophylls can be obtained in a short period of time using a method with a significant industrial advantage, allowing to eliminate the above-mentioned problems.

Accordingly, the present invention provides a method of obtaining a mono - or poliekilenov of xanthophyll, consisting in the oxidation of carotenoid that is found in a lower oxidation state than get xanthophyll, aqueous solution of hydrogen peroxide in the presence of water-immiscible organic solvent, and the above oxidation reaction is carried out in the presence of iodine-containing compounds.

In the present invention, the term "mono - and paleocology xanthophyll" refers to xanthophyll containing at least one atom of oxygen. Examples of these xanthophylls can be lutein, zeaxanthin, capsorubin, capsanthin, cantaxanthin is astaxanthin. The carotenoid in the lower oxidation state is a carotenoid as betacarotene, lutein or zeaxanthin.

According to a preferred embodiment of the method of the present invention is intended to obtain cantaxanthin and carotene in a lower oxidation state, such as betacarotene.

In accordance with another preferred embodiment of the method of the present invention is designed to produce astaxanthin and carotenoid in a lower oxidation state, such as lutein or zeaxanthin.

The method of the present invention involves the use of an aqueous solution of hydrogen peroxide. The concentration of the specified solution is 1-85 wt.%. The most preferred concentration is 25-55 wt.%.

In the method of the present invention requires the use of an organic solvent which is not miscible with water. Examples of such organic solvents can serve as halogenated hydrocarbons, for example methylene chloride, chloroform, carbon tetrachloride, monochlorobenzene, or dichloroethane; aromatic hydrocarbons such as benzene, toluene or xylene; aliphatic hydrocarbons such as pentane, hexane, cyclohexane or heptane; ethers like diethyl ether, diisopropyl ether or methyl tributyl ether; ester is as methyl acetate, ethyl acetate, butyl acetate or isopropylacetate. The organic solvent may be used in one or more forms. The preferred solvent is a halogenated hydrocarbon, especially monochlorbenzene and chloroform. The organic solvent may be used in an amount 2-300 times exceeds the amount of carotenoid.

The method of the present invention can be carried out in the presence of water, in other words, water can be used in addition to the aqueous solution of hydrogen peroxide. The amount of water present may be 0.2 to 50 by weight of the carotenoid, preferably 10-30 by weight of the carotenoid.

The method of the present invention requires the use of iodine-containing compounds. This connection initiates the oxidation reaction. Iodine-containing compound used in the method of the present invention may be an iodine halide derivative of iodine or iodide of a metal, or a mixture thereof. In the reaction mixture may contain two or more of these compounds. Examples of the halide derivatives of iodine that can be used in the present invention, can serve chloride iodine, iodine trichloride and tribromide iodine. Examples of metal iodides used in the present invention, can serve as the iodides of lithium, sodium, potassium, silver, calcium, whom Agnes, copper (I) and copper (II). The preferred compounds are iodine or iodide of an alkali metal such as sodium iodide or potassium.

The total amount of iodine-containing compound is usually 1 to 40 mol.%, preferably, 15-25 mol.% the amount of carotenoid.

When adding two or more iodine-containing compounds in the reaction mixture containing a carotenoid, an aqueous solution of hydrogen peroxide and an organic solvent, the following compounds can be added separately or in mixture with each other. Iodine-containing compound can be added to the reaction mixture continuously, portions or immediately. Preferably, the specified iodine-containing compound is added in a single aliquot.

Iodine-containing compound can be added to the reaction mixture in solid form or in the form of a solution in an appropriate solvent, for example, using an iodide of a metal suitable form is an aqueous solution, and the use of iodine or halide derivative of iodine suitable form is its solution in an organic solvent.

When you use beta-carotene as a substrate subject to oxidation by the method of the present invention, this method results in cantaxanthin. Beta-carotene is a commercially available product, which can also be obtained by any of the local method, for example, those disclosed in European Patent Application 00128048.6.

When using lutein or zeaxanthin as substrates that are subject to oxidation by the method of the present invention, the result is astaxanthin. Lutein and zeaxanthin are commercially available products, which can also be obtained by extraction of material of natural origin, especially calendula flowers (Targetes erecta), or any known method.

The method of the present invention can be carried out at a pH of 2-10, preferably 5-8, at a temperature of 10-50°preferably 20-30°C.

The method of the present invention preferably in an atmosphere of inert gas such as nitrogen or argon.

The oxidation reaction according to the present invention is preferably carried out with sufficient stirring.

Over the course of the oxidation reaction according to the present invention can be monitored by any of the analytical methods known to the expert. For this purpose you can use thin-layer chromatography (TLC) or liquid chromatography high resolution (HPLC; IHVR). The completion time of reaction may vary depending on the reaction conditions, but is usually 5 are 300 minutes.

After completion of the reaction the resulting xanthophyll can be isolated by conventional methods known to the expert in D. the authorized area. This method may be the maturation of the reaction mixture before separation into two phases, for example in an aqueous phase and an organic phase; collecting the organic phase; if it is necessary, in the washing of the specified organic phase in an aqueous solution of a reducing agent (e.g., thiosulfate of an alkali metal or alkali metal sulfate and removing the organic solvent from the organic phase to collect crystalline crude xanthophyll.

Then the crude xanthophyll may be subjected to isomerization to the TRANS-isomer. The isomerization can be performed classical methods such as thermal isomerization in a hot solvent (water, an alcohol like methanol, ethanol or isopropanol; a ketone such as acetone, methyl ethyl ketone; hydrocarbons as hexane, cyclohexane or heptane).

Received xanthophyll may be subjected to additional cleaning using such classical methods known to the expert as column chromatography or recrystallization.

Information confirming the possibility of carrying out the invention

Further, the present invention is illustrated by the following examples:

Example 1: Getting canthaxanthin from β-carotene using chloroform as solvent

In a three-neck flask equipped with a drip Raven is Oh, thermometer and reflux condenser, was downloaded β-carotene (1,988 g and 3.59 mmole, 97%), chloroform (70 ml, 103,7 g), hydrogen peroxide (30 wt.%, 4.09 to EQ, 14,69 mmole, 1.5 ml, 1,665 g). Then the reaction mixture was stirred at ambient temperature and one portion was added a solution of iodine (from 0.90 mmole, 0,228 g in 6 ml of chloroform). The resulting mixture was stirred for 5 hours. By this time β-carotene disappeared, and the pH of the solution was set at a value of 7. Then added 200 ml of thiosulfate, and the mixture was stirred for 15 minutes. The mixture to stand until it separates into two phases (upper phase = water, lower phase = organic phase). The organic phase was collected and the solvent was removed under reduced pressure, resulting in the obtained crude crystalline product. The crude product was mixed with 7.5 ml of acetone and heated under conditions of reflux distilled during the night. After cooling to 4°With crystalline canthaxanthin was collected by filtration (837 mg, yield 40%, the amount of TRANS-isomers >98%). The analysis by the HPLC method (IHVR), confirmed that the obtained product is canthaxanthin (figure 1). Mother liquor contained a mixture of isomeric canthaxanthine (the ratio of TRANS/CIS 50/50).

Example 2: Obtaining canthaxanthin from β-carotene using monochlorbenzene, as solvent

In Trekhgorny the flask, equipped with addition funnel, thermometer and reflux condenser, was downloaded β-carotene (1 g, 1,863 mmole, 97%), monochlorobenzene (20 ml, 22,14 g), hydrogen peroxide (30 wt.%, 4.2 EQ, 7,823 mmole, of 0.90 ml, 0,99 g). Then the reaction mixture was stirred at ambient temperature and one portion was added solid iodine (0.25 EQ, 0,4655 mmole, 118 mg). The resulting mixture was stirred for 90 minutes. By this time β-carotene disappeared and the pH of the solution was set at a value of 7. The resulting mixture was allowed to stand to separate into 2 phases (upper phase = water, lower phase = organic phase). The organic phase was collected and consecutively washed with 15 ml of 2% aqueous sodium thiosulfate solution and 15 ml of water. The solvent was removed under reduced pressure to obtain 1.1 g of the crude crystalline product, which was identified by the method GHUR as canthaxanthin (mixture of isomers) (figure 2).

1. The method of obtaining mono - or poliekilenov of xanthophyll, consisting in the oxidation of carotene in a lower oxidation state than the receivable xanthophyll, the system of the aqueous solution of hydrogen peroxide and an organic solvent, and the specified solvent not miscible with water, and the above oxidation reaction is carried out in the presence of iodine-containing compounds selected from the group comprising iodine, Gal is idea derived iodine and iodide of the metal.

2. The method according to claim 1, in which mono - or policykey xanthophyll is cantaxanthin and the specified carotenoid in a lower oxidation state is a beta-carotene.

3. The method according to claim 1, in which mono - or policykey xanthophyll astaxanthin is a, and the specified carotenoid in a lower oxidation state is lutein or zeaxanthin.

4. The method according to any one of claims 1 to 3, wherein said aqueous solution of hydrogen peroxide has a concentration 1-85 wt.%.

5. The method according to claim 4, wherein said aqueous solution of hydrogen peroxide has a concentration of 25-55 wt.%.

6. The method according to any one of claims 1 to 5, in which the organic solvent immiscible with water is used in excess in the 2-300 times the weight of the carotenoid.

7. The method according to claim 1, in which the specified iodine-containing compound is an iodine.

8. The method according to claim 1, in which the specified iodized compound is an iodide of an alkali metal.

9. The method according to any one of claims 1, 7 and 8, in which the number specified iodine-containing compound is between 1 and 40 mol% of the amount of carotenoid.

10. The method according to any one of claims 1 to 9, held at pH 2-10.

11. The method according to any one of claims 1 to 10, characterized in that it is carried out at a temperature from -10 to 50°C.