CN114369048B - Method for catalytic synthesis of astaxanthin - Google Patents

Method for catalytic synthesis of astaxanthin Download PDF

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CN114369048B
CN114369048B CN202111569916.5A CN202111569916A CN114369048B CN 114369048 B CN114369048 B CN 114369048B CN 202111569916 A CN202111569916 A CN 202111569916A CN 114369048 B CN114369048 B CN 114369048B
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astaxanthin
compound
ethanol
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CN114369048A (en
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朱文凯
任光明
邱金倬
梁尧尧
胡松涛
常相清
许伟
刘阳
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Zhejiang NHU Co Ltd
Shangyu NHU Biological Chemical Co Ltd
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Shangyu NHU Biological Chemical Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/09—Geometrical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

A method for catalytic synthesis of astaxanthin, comprising the steps of: 1) Placing the compound II and the compound III together in a solvent according to a molar ratio of 2.05-2.1:1, adding weak base, stirring, mixing and cooling to a temperature of-25 ℃ to-10 ℃; 2) Dropwise adding alkali liquor into the reaction mixture of the step 1) in a continuous mode at the temperature of minus 25 ℃ to minus 10 ℃, wherein the molar ratio of alkali in the alkali liquor to the compound II is 1.4-2.5:1; 3) After the reaction is completed, acid is added for neutralization, extraction and separation are carried out, and an organic phase is concentrated to obtain the compound I.

Description

Method for catalytic synthesis of astaxanthin
Technical Field
The invention relates to a cyclohexane derivative with at least four carbon atoms and an acyclic unsaturated side chain substituted by a six-membered non-aromatic ring, in particular to a preparation method of astaxanthin.
Background
Astaxanthin, also known as Astaxanthin, is a fat-soluble carotenoid known by the english name Astaxanthin and by the chemical name 3,3' -dihydroxy-4, 4' -diketo-beta, beta ' -carotene of formula C 40 H 52 O 4 The molecular weight 596.86 is a reddish brown to brown powder, and has high heat resistance and poor light resistance. It has unique coloring function, oxidation resistance, cancer resistance, ultraviolet injury resistance and other functions, and may be used widely in food, feed, cosmetics, medicine and other fields. The chemical structure is formed by connecting four isoprene units in conjugated double bond form, and two isoprene unit groups are arranged at two endsThe six-section ring structure is formed as follows:
the chemical synthesis process route of astaxanthin has the advantage of lower cost, and the synthesis route is as follows: 2c15+c10=c40; c20+2c10=c40; three synthetic routes of canthaxanthin as raw material. 2c15+c10=c40 is a main route for industrial production of astaxanthin, which adopts a reaction of C15 phosphine salt and C10 dialdehyde to generate WITTIG under the action of alkali, the alkali is mainly strong base, such as hydroxide or alkoxide of alkali metal as described in patent document DE19509955A1, and patent document CN101454280B uses strong alkali sodium methylate, but the strong alkali is too strong in the process of synthesizing astaxanthin, which can cause the generation of byproducts such as astaxanthin and half shrimp, thereby reducing the yield of the reactants, ensuring that the reaction conditions are not easy to control, ensuring strict control requirements of the reaction conditions, and having certain difficulty in industrial production. The synthetic method of final formation of astaxanthin by WITTIG reaction using butylene oxide as a weak base has been reported (eur.j. Org. Chem.2000, 829-836), and the advantage of using a weak base butylene oxide is that anions of phosphine salts (e.g. bromide ions) are trapped and thus chemically bonded, but butylene oxide is a relatively expensive carcinogen and is flammable and explosive in itself, and is more unsuitable for use in green-lasting chemical production. For this reason, further improvement of the synthetic astaxanthin route 2c15+c10=c40, and improvement of the reaction yield is a problem to be solved in the prior art.
Disclosure of Invention
Aiming at the problems, the invention provides a method for synthesizing astaxanthin by catalysis, which has the advantages of simple and safe catalyst source, high yield, easy control of process conditions, less side reaction and the like.
In order to solve the problems, the technical scheme provided by the invention is as follows:
a method for synthesizing astaxanthin by catalysis,
the reaction is as follows
The method comprises the following steps:
a method of catalytically synthesizing astaxanthin, the method comprising the steps of:
1) Dissolving a compound II and a compound III in a solvent, adding weak base, stirring, mixing and cooling at-25 ℃ to-10 ℃;
2) Adding strong alkali solution into the reaction mixture in the step 1) at the temperature of between 25 ℃ below zero and 10 ℃ below zero to react;
3) After the reaction is completed, acid is added for neutralization, extraction and separation are carried out, and an organic phase is concentrated to obtain the compound I.
The method for synthesizing astaxanthin by catalysis comprises the following steps: in step 1), the weak base is selected from sodium salt or potassium salt of organic weak acid, preferably the weak base is selected from one or more of sodium benzoate, sodium phenolate, sodium formate, sodium oxalate, sodium acetate, potassium benzoate, potassium formate, potassium oxalate and potassium acetate.
The method for synthesizing astaxanthin by catalysis comprises the following steps: in step 2), the strong base solution is a homogeneous solution or suspension selected from the group consisting of alkali metal alkoxides, alkali metal hydroxides, butyl lithium; the strong alkali solution is a homogeneous solution or suspension of sodium hydroxide or potassium hydroxide in ethanol, the ethanol for preparing the strong alkali solution has a water content of 8-10% by weight, and the mass ratio of the strong alkali solution to dichloromethane in the solvent is 0.7-0.8: 1.
the molar ratio of the alkali in the strong alkali solution to the compound II is 1.4-2.5:1, preferably 1.4-1.8:1.
The method for synthesizing astaxanthin by catalysis comprises the following steps: in the step 1), the molar ratio of the compound II to the compound III is 2.0-2.2:1; the molar ratio of the weak base to the compound II is 0.5-1.5: 1, preferably 0.8 to 1.2:1.
the method for synthesizing astaxanthin by catalysis comprises the following steps: in step 1), the solvent is selected from an alcohol solvent, a mixture of different alcohol solvents or a mixed solvent consisting of an alcohol and a non-polar solvent which is not miscible with water, preferably, the alcohol solvent is selected from methanol, ethanol, 1-propanol, 2, propanol, n-butanol; the non-polar solvent which is not miscible with water is selected from dichloromethane, ethyl acetate, methyl acetate, cyclohexane or toluene.
The method for synthesizing astaxanthin by catalysis comprises the following steps: in the step 1), the solvent is ethanol and methylene dichloride with the mass ratio of 0.3-0.4:1, and the water content of the ethanol in the solvent is 8-10% by weight; the mass ratio of the solvent to the compound II is 4: 13-14.
The method for synthesizing astaxanthin by catalysis comprises the following steps: in the step 2), the strong alkali solution is dripped into the reaction mixture in the step 1) in a continuous mode, the reaction time of dripping the strong alkali solution into the reaction mixture in the step 1) is 4-10 hours, preferably 4-6 hours, and after dripping, the reaction is carried out at the temperature of minus 25 ℃ to minus 10 ℃ for 1-6 hours, preferably 3-5 hours.
The method for synthesizing astaxanthin by catalysis comprises the following steps: in step 3), the acid is 5% dilute sulfuric acid or glacial acetic acid, and the acid is neutralized to a pH value of 2-7, preferably 3-5.
The method for synthesizing astaxanthin by catalysis further comprises the following step 4): and 3) adding ethanol into the compound I obtained by concentrating the organic phase in the step 3), heating and refluxing for 3-4 hours, converting astaxanthin into a full- (E) -isomer through thermal isomerization, and then cooling, filtering and drying to obtain an astaxanthin finished product.
The invention provides a method for synthesizing astaxanthin by catalysis, which adopts weak alkali sodium formate, sodium acetate and sodium oxalate as phase transfer catalysts for wittig reaction, and H is removed in the reaction process + Firstly, reacting with weak base to generate corresponding weak acid, and promoting forward progress of wittig reaction; the weak acid then reacts with potassium hydroxide/sodium hydroxide to form the corresponding weak base. Compared with the prior art, the method has the following beneficial effects: (1) The new method uses weak alkali sodium formate, sodium acetate and sodium oxalate as phase transfer catalysts for wittig reaction, and has simple, safe and environment-friendly catalyst sources and lower economic cost; (2) Less by-products such as hemi-astaxanthin and astaxanthin are formed in the process of the present invention by the above preferred methodsThe technological conditions are that the content of the semi-astaxanthin and the astaxanthin is reduced to the minimum value, the content of the semi-astaxanthin is reduced to less than 0.9 percent, and the content of the astaxanthin is reduced to less than 0.4 percent, and (3) the technological conditions in the method are easier to control, and the condition requirements are simple. Astaxanthin obtained by the process of the present invention is largely converted into the particularly desirable all- (E) -isomer (all-trans astaxanthin) by thermal isomerisation (usually by heating in ethanol).
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The molar yield of all-trans astaxanthin calculated on the basis of the compound III used = astaxanthin finished product mass x all-trans astaxanthin content/596.86 x 164/5.65
Comparative example 1
Preparing strong alkali liquor: 5.2g of sodium hydroxide was placed in a single-necked flask, 70g of ethanol (water content: 10 wt%) was added thereto, and the mixture was stirred and dissolved until the solution was transparent, and no significant sodium hydroxide remained, and transferred to a constant pressure dropping funnel.
At the beginning of the reaction, a 500ml four-necked flask was purged with nitrogen for at least 10min. Then, 40g of compound II, 5.65g of compound III, 100g of dichloromethane and 40g of ethanol (the water content is 10 wt%) are placed in a flask, when the mixed solution in the flask is cooled to-20 ℃, sodium hydroxide is dropwise added, the dropwise adding speed is controlled, the dropwise adding is carried out for 4 hours, after the dropwise adding is finished, stirring and heat preservation reaction are carried out at-15 ℃ for 3 hours, and the reaction process is monitored. After the reaction, neutralization was carried out with 7.8g of glacial acetic acid at constant temperature.
The neutralized reaction mixture was then washed 4 times with 200ml of water, respectively, and during the water washing, 50ml of dichloromethane were used for extraction each time, and the oil phase was separated off and collected. Concentrating the oil phase by vacuum distillation to recover 200-230ml dichloromethane, and stopping concentrating.
300ml of ethanol was added to the concentrated material, and the mixture was heated in a heating apparatus at 100 ℃. Then, 100ml of the solvent was extracted at an internal temperature of about 78℃and a heat source of 100℃and 100ml of ethanol was added thereto, followed by total reflux for 3 hours under boiling point conditions.
After total reflux, cooling the material to 20-30 ℃, carrying out suction filtration, flushing a filter cake with 50ml of ethanol for 2 times, and then placing the filter cake in a vacuum drying oven for drying for 6 hours to obtain 18.43g of astaxanthin finished product;
yield: according to high performance liquid chromatography detection, the product comprises: the total-trans astaxanthin content is 96.35%, the hemi-astaxanthin content is 1.21%, the astaxanthin content is 0.45%, and the cis-astaxanthin content is 0.45%; the molar yield of all-trans astaxanthin calculated on the basis of compound III was 86.36%
Comparative example 2 a 500ml four-necked flask was purged with nitrogen for at least 10 minutes. Then, 40g of compound II, 5.65g of compound III, 100g of dichloromethane, 40g of ethanol and 5.66g of sodium acetate were placed in a flask, and when the temperature of the mixed solution in the flask was reduced to-20 ℃, the reaction was kept at a temperature, and the reaction was monitored. Substantially non-reactive and no post-treatment was performed.
Example 1
Batch reaction material table
Preparing strong alkali liquor: 4.48g of sodium hydroxide was placed in a single-necked flask, 70g of ethanol (water content: 10%) was added thereto, and the mixture was stirred and dissolved until the solution was transparent, and no significant sodium hydroxide remained, and transferred to a constant pressure dropping funnel.
At the beginning of the reaction, a 500ml four-necked flask was purged with nitrogen for at least 10min. Then, 40g of compound II, 5.65g of compound III, 100g of dichloromethane, 40g of ethanol (water content of 10 wt%) and 5.74g of sodium acetate are placed in a flask, when the mixed solution in the flask is cooled to-20 ℃, the reinforced alkali solution is dripped, the dripping speed is controlled, after the dripping is finished, stirring and heat preservation reaction is continued for 3 hours at the temperature of less than-15 ℃, after the reaction is finished, 6.73g of glacial acetic acid is used for neutralization at the constant temperature.
The neutralized reaction mixture was then washed 4 times with 200ml of water, respectively, and during the water washing, 50ml of dichloromethane were used for extraction each time, and the oil phase was separated off and collected. Concentrating the oil phase by vacuum distillation to recover 200-230ml dichloromethane, and stopping concentrating.
300ml of ethanol was added to the concentrated material, and the mixture was heated in a heating apparatus at 100 ℃. Then, 100ml of the solvent was extracted at an internal temperature of about 78℃and a heat source of 100℃and 100ml of ethanol was added thereto, followed by total reflux for 3 hours under boiling point conditions.
After total reflux, cooling the materials to 20-30 ℃, carrying out suction filtration, flushing a filter cake with 50ml of ethanol for 2 times, and then placing the filter cake in a vacuum drying oven for drying for 6 hours; 20.07g of astaxanthin finished product is obtained
Yield: according to high performance liquid chromatography detection, the total-trans astaxanthin content in the product is 98.07%, the semi-astaxanthin content is 0.79%, the astaxanthin content is 0.23%, and the cis-astaxanthin content is 0.23%; the molar yield of all-trans astaxanthin calculated on the basis of the compound III used was 95.72%.
Monitoring the reaction processes of comparative examples 1, 2 and example 1, and comparing the influence of weak base on the reaction at-20 ℃ by taking sodium hydroxide as alkali, and finding that the reaction rate is relatively high and the trans-astaxanthin content is high by adding weak base into the mixed reaction solution; when the reaction liquid is only sodium hydroxide, the reaction rate is slower, and the trans-astaxanthin content is lower; when only weak base was added, C15 hardly reacted with C10.
Example 2
Batch reaction material table
Preparing strong alkali liquor: 5.04g of sodium hydroxide was placed in a single-necked flask, 80g of ethanol (water content: 8 wt%) was added thereto, and the mixture was stirred and dissolved until the solution was transparent, and no significant sodium hydroxide remained, and transferred to a constant pressure dropping funnel.
At the beginning of the reaction, a 500ml four-necked flask was purged with nitrogen for at least 10min. Then, 40g of compound II, 5.65g of compound III, 100g of dichloromethane, 40g of ethanol (water content of 8 wt%) and 3.81g of sodium oxalate are placed in a flask, when the mixed solution in the flask is cooled to-25 ℃, sodium hydroxide is dropwise added, the dropwise adding speed is controlled to be 4 hours, after the dropwise adding, stirring and heat preservation reaction are continued at the temperature of less than-20 ℃ for 3 hours, after the reaction is completed, 7.57g of glacial acetic acid is used for neutralization at a constant temperature.
The neutralized reaction mixture was then washed 4 times with 200ml of water, respectively, and during the water washing, 50ml of dichloromethane were used for extraction each time, and the oil phase was separated off and collected. Concentrating the oil phase by vacuum distillation to recover 200-230ml dichloromethane, and stopping concentrating
300ml of ethanol was added to the concentrated material, and the mixture was heated in a heating apparatus at 100 ℃. Then, 100ml of the solvent was extracted at an internal temperature of about 78℃and a heat source of 100℃and 100ml of ethanol was added thereto, followed by total reflux for 3 hours under boiling point conditions.
After total reflux, cooling the material to 20-30 ℃, carrying out suction filtration, flushing a filter cake with 50ml of ethanol for 2 times, and then placing the filter cake in a vacuum drying oven for drying for 6 hours to obtain 19.97g of astaxanthin finished product;
yield: according to high performance liquid chromatography detection, the total-trans astaxanthin content in the product is 97.85%, the hemi-astaxanthin content is 0.83%, the astaxanthin content is 0.21% and the cis-astaxanthin content is 0.36%; the molar yield of all-trans astaxanthin calculated on the basis of the compound III used was 95.03%
Example 3
Batch reaction material table
Preparing strong alkali liquor: 3.92g of sodium hydroxide was placed in a single-necked flask, 70g of ethanol (water content: 10 wt%) was added thereto, and the mixture was stirred and dissolved until the solution was transparent, and no significant potassium hydroxide remained, and transferred to a constant pressure dropping funnel.
At the beginning of the reaction, a 500ml four-necked flask was purged with nitrogen for at least 10min. Then, 40g of compound II, 5.65g of compound III, 100g of dichloromethane, 30g of ethanol (water content of 10 wt%) and 7.50g of sodium oxalate are placed in a flask, when the mixed solution in the flask is cooled to-15 ℃, potassium hydroxide is dropwise added, the dropwise adding speed is controlled for 4 hours, after the dropwise adding, stirring and heat preservation reaction are continued at the temperature of less than-10 ℃ for 3 hours, after the reaction is completed, 5.88g of glacial acetic acid is used for neutralization at a constant temperature.
The neutralized reaction mixture was then washed 4 times with 200ml of water, respectively, and during the water washing, 50ml of dichloromethane were used for extraction each time, and the oil phase was separated off and collected. Concentrating the oil phase by vacuum distillation to recover 200-230ml dichloromethane, and stopping concentrating
300ml of ethanol was added to the concentrated material, and the mixture was heated in a heating apparatus at 100 ℃. Then, 100ml of the solvent was extracted at an internal temperature of about 78℃and a heat source of 100℃and 100ml of ethanol was added thereto, followed by total reflux for 3 hours under boiling point conditions.
After total reflux, cooling the materials to 20-30 ℃, carrying out suction filtration, flushing a filter cake with 50ml of ethanol for 2 times, and then placing the filter cake in a vacuum drying oven for drying for 6 hours; 20.12g of astaxanthin product was obtained.
Yield: according to high performance liquid chromatography detection, the product contains 98.47% of all-trans astaxanthin, 0.64% of semi-astaxanthin, 0.18% of astaxanthin and 0.14% of cis-astaxanthin; the molar yield of all-trans astaxanthin calculated on the basis of the compound III used was 96.35%.
Example 4
Batch reaction material table
Preparing strong alkali liquor: 6.28g of potassium hydroxide was placed in a single-necked flask, 80g of ethanol (water content: 8 wt%) was added thereto, and the mixture was stirred and dissolved until the solution was transparent, and no significant potassium hydroxide remained, and transferred to a constant pressure dropping funnel.
At the beginning of the reaction, a 500ml four-necked flask was purged with nitrogen for at least 10min. Then, 40g of compound II, 5.65g of compound III, 100g of dichloromethane, 40g of ethanol (water content of 8 wt%) and 8.24g of potassium acetate are placed in a flask, when the mixed solution in the flask is cooled to-20 ℃, potassium hydroxide is dropwise added, the dropwise adding speed is controlled for 4 hours, after the dropwise adding, stirring and heat preservation reaction are continued at the temperature of less than-15 ℃ for 3 hours, after the reaction is completed, 6.73g of glacial acetic acid is used for neutralization at a constant temperature.
The neutralized reaction mixture was then washed 4 times with 200ml of water, respectively, and during the water washing, 50ml of dichloromethane were used for extraction each time, and the oil phase was separated off and collected. Concentrating the oil phase by vacuum distillation to recover 200-230ml dichloromethane, and stopping concentrating.
300ml of ethanol was added to the concentrated material, and the mixture was heated in a heating apparatus at 100 ℃. Then, 100ml of the solvent was extracted at an internal temperature of about 78℃and a heat source of 100℃and 100ml of ethanol was added thereto, followed by total reflux for 3 hours under boiling point conditions.
After total reflux, cooling the materials to 20-30 ℃, carrying out suction filtration, flushing a filter cake with 50ml of ethanol for 2 times, and then placing the filter cake in a vacuum drying oven for drying for 6 hours; 19.98g of astaxanthin product was obtained.
Yield: according to high performance liquid chromatography detection, the total trans-astaxanthin content of the product is 98.03%, the hemi-astaxanthin content is 0.76%, the astaxanthin content is 0.20% and the cis-astaxanthin content is 0.28%. The molar yield of all-trans astaxanthin calculated on the basis of the compound III used was 95.25%.

Claims (5)

1. A catalytic synthesis method of astaxanthin has the following reaction formula
Characterized in that the method comprises the steps of:
1) Dissolving a compound II and a compound III in a solvent, adding weak base, stirring, mixing and cooling at the temperature of-25 ℃ to-10 ℃;
the weak base is selected from one or more of sodium formate, sodium oxalate, sodium acetate, potassium formate, potassium oxalate and potassium acetate, the solvent is ethanol and methylene dichloride with the mass ratio of 0.3-0.4:1, and the water content of the ethanol is 8-10% by weight; the mass ratio of the solvent to the compound II is 4:13 to 14, wherein the molar ratio of the compound II to the compound III is 2.0 to 2.2:1, and the molar ratio of the weak base to the compound II is 0.5 to 1.5:1;
2) Dropping strong alkali solution into the reaction mixture of the step 1) in a continuous mode at the temperature of minus 25 ℃ to minus 10 ℃, wherein the reaction time of dropping strong alkali solution into the reaction mixture of the step 1) is 4 hours to 10 hours, and after dropping, the reaction is carried out for 3 hours to 5 hours at the temperature of minus 25 ℃ to minus 10 ℃; the strong alkali solution is a homogeneous solution or suspension of sodium hydroxide or potassium hydroxide in ethanol; the molar ratio of the alkali in the strong alkali solution to the compound II is 1.4-2.5:1, the water content of the ethanol in the prepared strong alkali solution is 8-10% by weight, and the mass ratio of the ethanol in the prepared strong alkali solution to the dichloromethane in the solvent is 0.7-0.8:1;
3) After the reaction is completed, adding acid for neutralization, extracting and separating, and concentrating an organic phase to obtain a compound I;
4): adding ethanol into the compound I obtained by concentrating the organic phase in the step 3), heating and refluxing for 3-4 hours, converting astaxanthin into a full- (E) -isomer through thermal isomerization, and then cooling, filtering and drying to obtain an astaxanthin finished product.
2. The method for catalytic synthesis of astaxanthin according to claim 1, wherein the molar ratio of alkali to compound II in the strong lye is 1.4-1.8:1.
3. The method for catalytic synthesis of astaxanthin according to claim 1, wherein the molar ratio of weak base to compound II is between 0.8 and 1.2:1.
4. the method for the catalytic synthesis of astaxanthin according to claim 1, wherein in step 2), the reaction time for dropping the strong base into the reaction mixture of step 1) is 4h to 6h.
5. The method for the catalytic synthesis of astaxanthin according to claim 1, wherein in step 3), the acid is 5% dilute sulfuric acid or glacial acetic acid, and is neutralized to a solution pH of 3-5.
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JPH0782246A (en) * 1993-09-04 1995-03-28 Basf Ag Manufacturing of astaxanthin
US5654488A (en) * 1995-03-18 1997-08-05 Basf Aktiengesellschaft Preparation of astaxanthin
CN101454280A (en) * 2006-05-10 2009-06-10 帝斯曼知识产权资产管理有限公司 Process for the preparation of as taxanthin
JP2018131390A (en) * 2017-02-13 2018-08-23 アスタファーマシューティカルズ株式会社 Method for producing optically active astaxanthin
CN113461583A (en) * 2021-07-06 2021-10-01 广州智特奇生物科技股份有限公司 Synthetic method of astaxanthin

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US20060111580A1 (en) * 2004-10-01 2006-05-25 Lockwood Samuel F Methods for the synthesis of chiral dihydroxy ketone intermediates useful for the chiral synthesis of carotenoids

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0782246A (en) * 1993-09-04 1995-03-28 Basf Ag Manufacturing of astaxanthin
US5654488A (en) * 1995-03-18 1997-08-05 Basf Aktiengesellschaft Preparation of astaxanthin
CN101454280A (en) * 2006-05-10 2009-06-10 帝斯曼知识产权资产管理有限公司 Process for the preparation of as taxanthin
JP2018131390A (en) * 2017-02-13 2018-08-23 アスタファーマシューティカルズ株式会社 Method for producing optically active astaxanthin
CN113461583A (en) * 2021-07-06 2021-10-01 广州智特奇生物科技股份有限公司 Synthetic method of astaxanthin

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