Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2001-03-19
2002-04-23
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S348000, C568S362000, C568S374000
Reexamination Certificate
active
06376717
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for preparing astaxanthin. Specifically, the process of the present invention demonstrates a novel conversion of zeaxanthin directly to astaxanthin. The invention can be accomplished in either one chemical step or in a sequence of two chemical steps.
2. Description of the Related Art
In nature, the reddish color of meat of anadromous fish such as salmon or sea trout and lobsters is due to red pigments such as astaxanthin, which is present in naturally occurring feeds such as crustaceans and other related astaxanthin containing species. Commercially, astaxanthin is an economically important natural carotenoid which is extensively used in aquaculture to induce natural color in certain species of fish, as the fish do not have access to these natural pigmentation sources. In addition, related xanthophylls are used as a food additive to enhance the yolk color of eggs in the poultry industry.
Astaxanthin isolated from crustacean wastes or produced synthetically have been used as constituents in fish feed. However, the synthetic manufacture of astaxanthin and the process for manufacture of natural astaxanthin are expensive and tedious. In particular, the material is prepared either by total synthesis, by algae culture or by bacterial fermentation (See, for example, U.S. Pat. Nos. 6,022,701, 6,015,684, 5,972,642 and 5,935,808). Manufacture by total synthesis is very laborious and costly, and invariably provides a complete mixture of isomers that are not normally found in nature. Likewise, the culturing of algae and the fermentation of bacteria only produce low yields of the desired product. In addition, these methods are tedious and very costly.
In spite of the natural and abundant availability of zeaxanthin coupled with the significant economic value of astaxanthin, surprisingly, the direct conversion of zeaxanthin to astaxanthin has not been described. It has been reported that dimethylzeaxanthin could be converted to dimethylastaxanthin, but the removal of the methyl groups could not be accomplished to produce astaxanthin (Surmatis and Tommen,
J. Org. Chem
. (1967) 32: 180). In fact, conversion reactions of this type are known to be very difficult and invariably result in the formation of further oxidation products (Cooper et al,
J. C. S. Perkins I
(1975) 2195). A large number of researchers have described the total synthesis of related carotenoids such as astaxanthin, but no attempts have been made for the conversion of one such carotenoid to another. Workers at BASF have demonstrated the conversion of beta-carotene to canthaxanthin by an oxidation process similar to the process described herein, but no attempts have been made to convert zeaxanthin to astaxanthin (U.S. Pat. No. 4,212,827).
Zeaxanthin can be obtained directly from natural sources or it can be prepared in good yields from lutein by previously describe methods (See Rodriguez, U.S. Pat. No. 5,973,211).
Therefore, it is evident that there is a need for an efficient industrial-scale method to convert readily available zeaxanthin to astaxanthin.
SUMMARY OF THE INVENTION
The present invention relates to method for preparing astaxanthin from zeaxanthin or 3,3′,4,4′-tetrahydroxy-&bgr;-carotene, which includes contacting the zeaxanthin or 3,3′,4,4′-tetrahydroxy-&bgr;-carotene with a halogenating agent in the presence of chloric or bromic acid or salts thereof Preferably, the halogenating agent is selected from the group including N-bromosuccinimide, bromine, pyridinium tribromide, iodine, and mixtures thereof either added directly or generated in situ with a compound selected from the group including sodium bromide, potassium bromide, sodium iodide and potassium iodide. The disclosed method may further include a reaction solvent system, wherein said reaction solvent is selected from the group including an organic solvent and water. In a preferred embodiment, the organic solvent is chloroform. In a more preferred embodiment, the halogenating agent is N-bromosuccinimide or pyridinium tribromide.
In a preferred embodiment, the halogenating agent is generated in situ from a mixture of an oxidizing agent and a compound selected from the group consisting of potassium bromide, sodium bromide, sodium iodide and potassium iodide. Preferably, the oxidizing agent is selected from the group including bromic acid, chloric acid and salts thereof and preferably, the mixture is acidic. In a most preferred embodiment, when the halogenating agent is generated in situ, the mixture includes a solution of sodium bromate and potassium bromide. In an alternate most preferred embodiment, the halogenating agent is generated in situ from a mixture which includes a solution of sodium iodine and sodium chlorate.
The present disclosure also relates to a method for preparing 3,3′,4,4′-tetrahydroxy-&bgr;-carotene from zeaxanthin, which includes contacting said zeaxanthin with a halogenating agent to form a mixture followed by contacting said mixture with a base. In a most preferred embodiment, the halogenating agent is N-bromosuccinimide and the base is an amine base. In an alternate preferred embodiment, the halogenating agent is selected from the group including N-bromosuccinimide, bromine, pyridinium tribromide, iodine, and mixtures thereof either added directly or generated in situ with a compound selected from the group including sodium bromide, potassium bromide, sodium iodide and potassium iodide. The method may further include a reaction solvent system, wherein the reaction solvent is selected from the group including an organic solvent and water. In a preferred embodiment, the organic solvent is chloroform. In a preferred embodiment of the method, the halogenating agent is N-bromosuccinimide and the amine base is N,N-diisopropylethylamine.
The present invention also relates to a method for preparing astaxanthin from 3,3′,4,4′-tetrahydroxy-&bgr;-carotene, which includes contacting said 3,3′,4,4′-tetrahydroxy-&bgr;-carotene with a mixture which includes a halogenating agent and an acid selected from the group including bromic acid, chloric acid and salts thereof. In a preferred embodiment, the halogenating agent is N-bromosuccinimide. The method may further include a reaction solvent system, wherein the reaction solvent is selected from the group including an organic solvent and water. In a preferred embodiment, the organic solvent is chloroform. In a preferred embodiment of the method, the halogenating agent is generated in situ from a mixture of an oxidizing agent and a compound selected from the group including potassium bromide, sodium bromide, sodium iodide and potassium iodide. In a most preferred embodiment the oxidizing agent is selected from the group including bromic acid, chloric acid, and salts thereof. In a preferred embodiment, the mixture is acidic. In a most preferred embodiment, when the halogenating agent is generated in situ, the mixture includes solutions of sodium bromate and potassium bromide. In an alternate most preferred embodiment, the mixture for generating the halogenating agent in situ includes solutions of sodium iodine and sodium chlorate.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention is directed to a method of treating zeaxanthin with oxidizing agents. Non-limiting examples of performing allylic oxidations or agents that may be employed in oxidation reactions have been reviewed in Barry M. Trost, Ed. and Ian Fleming, Ed. “
Comprehensive Organic Synthesis
,” Volume 7, Pergamon Press, New York, 1991, pages 83-117, and Richard C. Laro “
Comprehensive Organic Transformations
,” Wiley-VCH, New York, 1999, pages 1207-1209, which are incorporated herein in their entirety by reference. Preferably, the oxidizing agent is a halogenating agent in the presence of salts of chloric or bromic acids or salts of chlorate or bromates. More preferably, the halogenating agent is selected from the group consisting of N-bromosuccinamide, bromine, pyridini
Davis Jeffery L.
Schloemer George C.
Knobbe Martens Olson & Bear LLP
Prodemex, S.A. de C.V.
Richter Johann
Witherspoon Sikarl A.
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