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CN-121991120-A - Astaxanthin intermediate, astaxanthin and preparation method thereof

CN121991120ACN 121991120 ACN121991120 ACN 121991120ACN-121991120-A

Abstract

The invention relates to the technical field of organic synthesis, in particular to an astaxanthin intermediate, astaxanthin and a preparation method thereof. According to the invention, the astaxanthin intermediate can be prepared under normal pressure and low temperature by selecting a specific composite catalyst, so that side oxidation and peroxidation byproducts are effectively avoided, and the astaxanthin intermediate has higher yield.

Inventors

  • ZHANG YONGKANG
  • LIANG HAN
  • SHEN HONGQIANG
  • LI SHENGYONG
  • ZHANG YIYU

Assignees

  • 万华化学集团股份有限公司

Dates

Publication Date
20260508
Application Date
20260106

Claims (10)

  1. 1. A process for the preparation of an astaxanthin intermediate, comprising the steps of: Dissolving a compound I in an organic solvent to obtain an organic solution containing a compound 1, and carrying out an epoxidation reaction on the organic solution containing the compound 1 under the action of a composite catalyst by taking a hydrogen peroxide aqueous solution as an oxidant to obtain the astaxanthin intermediate; the structure of the compound 1 is as follows: The astaxanthin intermediate has the structure as follows: R is independently selected from C1-C4 alkyl groups each occurrence, rp is an acidolytically acceptable OH protecting group; wherein the composite catalyst comprises a silicon-titanium molecular sieve catalyst and a metal organic complex catalyst.
  2. 2. The preparation method according to claim 1, wherein the mass ratio of the total mass of the composite catalyst to the compound I is (0.01-0.5): 1.
  3. 3. The preparation method of the catalyst according to claim 1 or 2, wherein the mass ratio of the silicon-titanium molecular sieve catalyst to the metal organic complex catalyst in the composite catalyst is (1-5): 1-3.
  4. 4. The preparation method of any one of claims 1-3, wherein the molar ratio of Si to Ti in the silicon-titanium molecular sieve catalyst is 20-100:1; preferably, the silicon-titanium molecular sieve type catalyst is at least one selected from Ti-SBA-15, ti-MCM-41 and TS-1 molecular sieves; Preferably, the metal content of the metal organic complex catalyst is 0.5-5 wt%; preferably, the metal content of the metal organic complex catalyst is 1-3 wt%; preferably, the active metal in the metal organic complex catalyst is selected from one or more of Mn, mo, W, ti, cr; more preferably, the active metal in the metal organic complex catalyst is selected from Mn, mo, W; Preferably, the metal organic complex catalyst is selected from at least one of Mn-Salen/SiO 2 、MoO 2 (acac) 2 /SiO 2 、WO 3 -Salen/SiO 2 .
  5. 5. The method according to any one of claims 1 to 4, wherein the mass concentration of hydrogen peroxide in the aqueous hydrogen peroxide solution is 20 to 50%; preferably, the mass concentration of hydrogen peroxide in the aqueous hydrogen peroxide solution is 30%; Preferably, the organic solvent is selected from one or more of toluene, dichloromethane, ethyl acetate and acetonitrile; Preferably, the organic solvent is at least one selected from toluene and methylene chloride.
  6. 6. The process according to any one of claims 1 to 5, wherein the epoxidation reaction is carried out by adding an aqueous hydrogen peroxide solution to an organic solution containing compound 1; preferably, the molar ratio of the addition amount of the hydrogen peroxide to the compound 1 is (0.8-2.5): 1; preferably, the aqueous hydrogen peroxide solution is added at a constant rate; Preferably, the adding time of the hydrogen peroxide water solution is 0.5-3 hours; preferably, the adding time of the hydrogen peroxide water solution is 1-2 hours; Preferably, the epoxidation reaction temperature is 0-40 ℃; preferably, the epoxidation reaction temperature is 5-15 ℃; Preferably, the epoxidation reaction time is 2-10 hours; preferably, the epoxidation reaction time is 3-5 hours.
  7. 7. An astaxanthin intermediate, characterized in that it is prepared by the preparation method according to any one of claims 1 to 6.
  8. 8. The preparation method of astaxanthin is characterized by comprising the following steps: 1) Reacting the astaxanthin intermediate with halogen acid to obtain a ring-opening product; 2) Reacting the ring-opened product with triphenylphosphine to obtain C15 phosphine salt; Wherein X is halogen, R, rp 3) Carrying out Wittig reaction and isomerization reaction on C15 phosphine salt and C10 dialdehyde to obtain astaxanthin; 。
  9. 9. the method of claim 8, wherein the reaction of the astaxanthin intermediate with the halogen acid is performed in an organic solvent; Preferably, the hydrohalic acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, hydroiodic acid, Preferably, the molar ratio of the astaxanthin intermediate to the hydrogen halide in the halogen acid is 1:0.5-2.5; preferably, the astaxanthin intermediate is reacted with the halogen acid at a temperature of 20~20°C; Preferably, the molar ratio of the triphenylphosphine in the step 2) to the hydrogen halide in the halogen acid in the step 1) is 0.5-2.5:1; preferably, the reaction temperature of the ring-opened product and triphenylphosphine is 0-50 ℃, and the reaction time is 12-48 h.
  10. 10. Astaxanthin, characterized in that it is obtained by the preparation method according to claim 8 or 9.

Description

Astaxanthin intermediate, astaxanthin and preparation method thereof Technical Field The invention relates to the technical field of organic synthesis, in particular to an astaxanthin intermediate, astaxanthin and a preparation method thereof. Background Astaxanthin (astaxanthin, molecular formula C 40H52O4, structure shown below) is a non-provitamin A carotenoid. Astaxanthin has the functions of resisting oxidation, coloring, regulating immunity and the like, and has wide application in cosmetics, health products, foods and feed additives. For example, the use of astaxanthin in sunscreens can reduce damage, and the use of astaxanthin in salmon culture can make fish meat appear bright orange red, thereby improving commodity value. As consumer demand for healthy products increases, the astaxanthin industry will continue to evolve at a high rate. Sources of astaxanthin include natural extraction and chemical synthesis. Natural astaxanthin is mainly derived from haematococcus pluvialis extraction and yeast fermentation, but has a small market share due to high cost. In contrast, chemically synthesized astaxanthin occupies the major market today and is used entirely in animal feed additives. On the synthesis route, according to different carbon numbers of raw materials, the main manufacturers adopt a route of C15+C10+C15=C40, namely, C15 firstly generates C15 phosphine salt, and then reacts with C10 through a winting reaction to obtain C40. Key to this route is the preparation of the C15 intermediate, i.e. 3-hydroxy-4-oxovinyl- β -ionol. At present, the industrialized route for preparing 3-hydroxy-4-oxo vinyl-beta-ionol is a C9+C6 route, which takes theaaroma ketone as a raw material, and the 3-hydroxy-4-oxo vinyl-beta-ionol is generated through 7 steps of reactions, so that the synthetic route is longer and the operation is complicated. BASF reported in CN103917549 in 2012 that 4-oxo-vinyl- β -ionol was used as a raw material, firstly hydroxy group protection and silyl enol etherification were performed under alkaline conditions, and then epoxidation, ring opening and hydrolysis were performed with peroxyacid to obtain 3-hydroxy-4-oxo-vinyl- β -ionol. The patent does not mention the yield of 3-hydroxy-4-oxovinyl-beta-ionol. In the process, two problems 1) exist, namely, peroxycarboxylic acid is needed in the preparation process of an epoxidation intermediate product, the industrial use has a large potential safety hazard, the epoxidation process is not easy to control, excessive oxidation is easy to generate a double oxidation by-product, and meanwhile, the oxidation by-product (such as m-chlorobenzoic acid generated after m-chloroperoxybenzoic acid is used) is not easy to dispose. 2) In the preparation of C15 phosphine salts, the hydrolysis reaction is usually carried out under acidic or basic conditions, while 3-hydroxy-4-oxo-vinyl- β -ionol is potentially unstable under both acidic and basic conditions, resulting in the formation of hydrolysis byproducts and a reduced reaction yield. For example, B.G. Britton, S. Liaaen-Jensen, H. Pfander, carotenoids, vol.2, birkhauser Verlag, basel, 1996 mentions that in the synthesis of astaxanthin it has to be remembered that all products with partial structure I may irreversibly form the cumyl phenol structure II under the action of strong acids or bases, 。 In addition, enolization of 1, 2-dione III, a dehydrogenation by-product, is easily formed. The production of the series of potential byproducts causes the difficulty of separation and purification of the reaction route and reduces the reaction yield. The above two problems limit the industrial use of this route. Disclosure of Invention The invention provides a preparation method of an astaxanthin intermediate, which aims to solve the problems of greater potential safety hazard and more byproducts in the prior art for preparing the astaxanthin intermediate. The invention also provides a preparation method of astaxanthin, which aims to solve the problems of more byproducts and lower astaxanthin yield in the process of preparing astaxanthin in the prior art. In a first aspect, the invention provides a process for the preparation of an astaxanthin intermediate, comprising the steps of: Dissolving a compound I in an organic solvent to obtain an organic solution containing a compound 1, and carrying out an epoxidation reaction on the organic solution containing the compound 1 under the action of a composite catalyst by taking a hydrogen peroxide aqueous solution as an oxidant to obtain the astaxanthin intermediate; the structure of the compound 1 is as follows: The astaxanthin intermediate has the structure as follows: R is independently selected from C1-C4 alkyl groups each occurrence, rp is an acidolytically acceptable OH protecting group; wherein the composite catalyst comprises a silicon-titanium molecular sieve catalyst and a metal organic complex catalyst. It will be appreciated that the epoxidation reaction may be