Process for preparing astacene

Patent metadata

Field	Value
Publication number	US-10836718-B2
Application number	US-201716462992-A
Country	US
Kind code	B2
Filing date	Nov 20, 2017
Priority date	Nov 25, 2016
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

The invention describes a process for making astacene of formula 1, the exocyclic double bonds thereof having either an E configuration or an E- and/or Z-configuration, wherein astaxanthin of the general formula 2 having asymmetric centers 3 and 3′, each of which respectively having an (S)- or (R)-conformation and the exocyclic double bonds of said astaxanthin 2 having either an E- or E- and/or Z configuration, is oxidized in the presence of at least one tertiary alcoholate.

First claim

The invention claimed is:

1. A process for making astacene of formula (1), the exocyclic double bonds thereof having either an E configuration or an E- and/or Z-configuration

wherein astaxanthin of the general formula (2)

having asymmetric centers 3 and 3′, each of which respectively having an (S)- or (R)-conformation and the exocyclic double bonds of said astaxanthin (2) having either an E- or E- and/or Z configuration,
is oxidized in the presence of at least one tertiary alcoholate.

2. The process according to claim 1 , wherein the at least one tertiary alcoholate is a tertiary C4-C6 alcoholate.

3. The process according to claim 1 , wherein astaxanthin of the general formula (2) is oxidized in the presence of at least one metal salt.

4. The process according to claim 3 , wherein the metal salt is a transition metal salt selected from the group of salts of transition metals and/or from the group of oxides of transition metals.

5. The process according to claim 3 , wherein the metal salt is a transition metal salt selected from the group of divalent and/or trivalent salts of transition metals of the group consisting of Mn(II), Co(II), Fe(II), Cu(II) and Ru(III).

6. The process according to claim 3 , wherein the metal salt comprises at least one anion.

7. The process according to claim 1 , wherein the astaxanthin of the general formula (2) is oxidized in the presence of at least one nitrogen compound, said at least one nitrogen compound being selected from the group consisting of, tertiary amines, pyridine, diamines and dipyridine.

8. The process according to claim 1 , wherein the astaxanthin of the general formula (2) is oxidized in a time ranging from 0.25 h to 6 h.

9. The process according to claim 1 , wherein the astaxanthin of the general formula (2) is oxidized in an atmosphere of an inert gas or in an atmosphere of a mixture of air and an inert gas, or in an air atmosphere, preferably in an atmosphere of an inert gas or in an atmosphere of a mixture of air and an inert gas, said respective atmospheres comprise from 0 to 50 vol % of oxygen.

10. The process according to claim 1 , wherein the astaxanthin of the general formula (2) is oxidized in an atmosphere of an inert gas or in an atmosphere of a mixture of air and an inert gas, or in an air atmosphere, preferably in an atmosphere of an inert gas or in an atmosphere of a mixture of air and an inert gas, said respective atmospheres comprise from 7 to 15 vol % of oxygen.

11. A process for preparing from a mixture of various astaxanthin isomers referred to as astaxanthin of the general formula (2)

an enantiomerically pure astaxanthin of formula (3) or of formula (5),
or an astaxanthin highly enriched in astaxanthin of formula (3) or of formula (5), wherein
a) astaxanthin of the general formula (2) is oxidized in a solvent or in a solvent mixture in the presence of at least one tertiary alcoholate according to claim 1 , to form astacene of formula (1),
b) astacene of formula (1) is reduced by means of an enantioselective transfer hydrogenation to form 3S,3′S-astaxanthin of formula (3),

or 3R,3′R-astaxanthin of formula (5)

with the exocyclic double bonds of 3S,3′S-astaxanthin of formula (3) or of 3R,3′R-astaxanthin of formula (5) having either an E- or E- and/or Z configuration.

12. The process according to claim 11 , wherein the astacene of formula (1) obtained in process step a), without any workup, is reduced by means of an enantioselective transfer hydrogenation to form 3S,3′S-astaxanthin of formula (3) or 3R,3′R-astaxanthin of formula (5).

13. The process according to claim 11 , wherein the enantioselective transfer hydrogenation is realized with a combination of formic acid and a transition metal catalyst, said transition metal catalyst comprises at least one ligand, which is selected from the group consisting of:
at least one optically active amine, which is preferably H 2 N—CHPh-CHPh-OH, H 2 N—CHMe-CHPh-OH, MeHN—CHMe-CHPh-OH, TsNH—CHPh-CHPh-NH 2 , (1S,2S)—N-p-toluene sulfonyl-1,2-diphenylethylene diamine, (1R,2R)—N-p-toluene sulfonyl-1,2-diphenylethylene diamine, N-[(1S,2S)-1,2-diphenyl-2-(2-(4-methylbenzyl-oxy)ethylamino)-ethyl]-4-methylbenzene sulfonamide or N-[(1R,2R)-1,2-diphenyl-2-(2-(4-methylbenzyloxy)ethylamino)-ethyl]-4-methylbenzene sulfonamide;
at least one optically active amino acid.

14. The process according to claim 11 , wherein the solvent or solvent mixture used in process step a) is partially or completely exchanged prior to process step b).

15. The process according to claim 11 , wherein after process step b) heating up to a temperature of 60 to 120° C., is realized in process step c).

16. The process according to claim 11 , wherein the process steps a), b) and c) are realized “onepot”.

17. A non-therapeutic preparation comprising enantiomerically pure astaxanthin of formula (3) or of formula (5), or an astaxanthin highly enriched in astaxanthin of formula (3) or of formula (5) all obtained with the process according to claim 11 .

18. A preparation for a pharmaceutical or medical use comprising enantiomerically pure astaxanthin of formula (3) or of formula (5), or an astaxanthin highly enriched in astaxanthin of formula (3) or of formula (5) all obtained with the process according to claim 11 .

19. The process according to claim 1 , wherein the astaxanthin of the general formula (2) is oxidized in an atmosphere of an inert gas or in an atmosphere of a mixture of air and an inert gas, said respective atmospheres comprise from 7 to 15 vol % of oxygen.

20. The preparation claimed in claim 18 , wherein the preparation contains 6 mg of enantiomerically pure or highly enriched astaxanthin of formula 3 or of formula 5, 15 IU of vitamin E, 75 w¾ of oleic acid, 20% of linoleic acid, 5 w % of palmitic acid with the weight amount of all fatty acids giving 100% and making from 60 to 80 w¾ of the preparation of pharmaceutical or medical use.

21. The process according to claim 11 , wherein the enantioselective transfer hydrogenation is realized with a combination of formic acid and a transition metal catalyst, said transition metal catalyst comprises at least one ligand, which is selected from the group consisting of:
H2N—CHPh-CHPh-OH, H2N—CHMe-CHPh-OH, MeHN—CHMe-CHPh-OH, TsNH—CHPh-CHPh-NH2, (1S,2S)—N-p-toluene sulfonyl-1,2-diphenylethylene diamine, (1R,2R)—N-p-toluene sulfonyl-1,2-diphenylethylene diamine, N-[(1S,2S)-1,2-diphenyl-2-(2-(4-methylbenzyloxy)ethylamino)-ethyl]-4-methylbenzene sulfonamide or N-[(1R,2R)-1,2-diphenyl-2-(2-(4-methylbenzyloxy)ethylamino)-ethyl]-4-methylbenzene sulfonamide; and
at least one optically active amino acid.

Assignees

• Basf Se

Inventors

• Schaefer Bernd
• Siegel Wolfgang

Classifications

• C07C403/24 Primary

  having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene · CPC title