Process for the preparation of alpha- and beta-cryptoxanthin

Abstract

The present invention relates to a process for converting lutein and/or lutein esters to (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin, suitable for human consumption as dietary supplements, by employing safe and environmentally friendly reagents. (3R)-β-Cryptoxanthin and (3R,6′R)-α-cryptoxanthin are two rare food carotenoids that are not commercially available and the former exhibits vitamin A activity. In the first synthetic step, commercially available lutein and/or lutein esters are transformed into a mixture of dehydration products of lutein (anhydroluteins) in the presence of a catalytic amount of an acid. The resulting anhydroluteins are then converted to (3R)-β-cryptoxanthin (major product) and (3R,6′R)-α-cryptoxanthin (minor product) by heterogeneous catalytic hydrogenation employing transition elements of group VIII (Pt, Pd, Rh supported on alumina or carbon) in a variety of organic solvents under atmospheric pressure of hydrogen and at temperatures ranging from −15° C. to 40° C. Among these catalysts, Pt supported on alumina at 40° C. in ethyl acetate provides the best yield of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin. Several homogeneous catalysts can also promote the regioselective hydrogenation of anhydroluteins to a mixture of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin in low to moderate yields. The catalysts may be transition metal complexes such as palladium acetylacetonate, Rh(Ph 3 P) 3 Cl (Wilkinson's catalyst), [(C 6 H 11 ) 3 P[C 8 H 12 ][C 5 H 5 N]Ir + PF6 − (Crabtree catalyst), or [C 8 H 12 ][(MePh 2 P) 2 ]Ir + PF6 − . Among these, Wilkinson catalyst converts anhydroluteins to (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin in nearly quantitative yield. A novel feature of this invention is the regioselective hydrogenation of anhydroluteins while the highly conjugated polyene chain of these carotenoids remains intact.

1 . A composition of matter comprising β- and α-cryptoxanthin produced using catalytic hydrogenation from products selected from the group consisting of lutein, lutein esters, anhydroluteins, and combinations of such products, wherein the ratio of β-cryotoxanthin to α-cryptoxanthin is at least 4:1.  
   
   
       2 . The composition of  claim 1 , wherein the products contain (3R,3′R,6′R)-lutein.  
   
   
       3 . The composition of  claim 1 , wherein the β-cryptoxanthin is (3R)-β-cryptoxanthin and the α-cryptoxanthin is (3R,6′R)-α-cryptoxanthin.  
   
   
       4 . The composition of matter of  claim 1 , wherein the β- and α-cryptoxanthin comprises at least 1 weight percent of the composition.  
   
   
       5 . A process for converting a product into β- and α-cryptoxanthin, comprising the steps of reacting the product in alcohol with a catalytic amount of acid at an elevated temperature to yield a mixture of anhydroluteins, and reacting the anhydroluteins with hydrogen in the presence of a Group VIII transition element catalyst in an organic solvent at a temperature not exceeding 100° C. to yield a mixture of cryptoxanthins.  
   
   
       6 . The method of  claim 5 , wherein the products contain (3R,3′R,6′R)-lutein and wherein the β-cryptoxanthin is (3R)-β-cryptoxanthin and the α-cryptoxanthin is (3R,6′R)-α-cryptoxanthin.  
   
   
       7 . The method of  claim 5 , wherein the temperature is between about −15° C. and about 80° C.  
   
   
       8 . The method of matter of  claim 5 , wherein the β- and α-cryptoxanthin comprises at least 1 weight percent of the composition.  
   
   
       9 . A process for converting a lutein product to a mixture of anhydroluteins I, II, III, comprising reacting in a single stage the lutein product in water and one or more alcohols, with a catalytic amount of an acid selected from the group consisting of aqueous mineral acids and strong organic acids, with stirring at an elevated temperature to give directly without the formation of an intermediate a mixture of anhydroluteins comprising anhydrolutein III as the major product with anhydroluteins I and II as minor products.  
   
   
       10 . The process of  claim 9 , wherein said alcohol is selected from the group consisting of ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, tert-butyl alcohol, 1-pentanol (n-amyl alcohol), 2-pentanol, n-hexyl alcohol, n-octyl alcohol, ethylene glycol, and propylene glycol.  
   
   
       11 . The process of  claim 9 , wherein said aqueous mineral acid is selected from the group consisting of aqueous hydrochloric acid, sulfuric acid and phosphoric acid, and the organic acid is selected from the group consisting of trifluoroacetic acid and trichloroacetic acid.  
   
   
       12 . The process of  claim 9 , wherein said elevated temperature is at the reflux temperature of the solvent.  
   
   
       13 . A process for converting (3R,3′R,6′R)-lutein esters containing (3R,3′R)-zeaxanthin esters to a mixture of anhydroluteins, comprising reacting a product containing the lutein esters in a solvent selected from the group consisting of hydrocarbons and ethers and at least one alcohol with a catalytic amount of an acid selected from the group consisting of aqueous mineral acids and organic acids at a temperature below 60° C. to obtain a mixture of lutein 3-acylesters 3′-alkyl ether, adding water and additional acid and raising the temperature to between about 78° C. and about 100° C. to convert lutein 3-acylesters 3′-alkyl ether to a crude mixture of anhydroluteins I, II, and III rich in anhydrolutein III.  
   
   
       14 . The process of  claim 13 , wherein the product containing the lutein esters are selected from crude extracts of marigold flowers.  
   
   
       15 . The process of  claim 13 , wherein said alcohol is selected from the group consisting of ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, tert-butyl alcohol, 1-pentanol (n-amyl alcohol), 2-pentanol, n-hexyl alcohol, n-octyl alcohol, ethylene glycol, and propylene glycol.  
   
   
       16 . The process of  claim 13 , wherein the aqueous mineral acid is selected from the group consisting of hydrochloric acid, sulfuric acid and phosphoric acid.  
   
   
       17 . The method of  claim 13 , further comprising hydrolyzing the lutein esters to remove the fatty acids and crystallizing the anhydroluteins.  
   
   
       18 . The process of  claim 13 , wherein the temperature is kept below 50° C. and a mixture of lutein 3-acylesters 3′-alkyl ether are first isolated without adding additional amounts of water, acid, and raising the temperature.  
   
   
       19 . The method of  claim 18 , further comprising cooling the solution comprising mixture of lutein 3-acylesters 3′-alkyl ether to ambient temperature and hydrolyzing the solution comprising the mixture of lutein 3-acylesters 3′-alkyl ether with an alcoholic solution of a mineral base and evaporating the solvents to obtain a concentrated residue containing lutein 3′-alkyl ether.  
   
   
       20 . The method of  claim 19 , further comprising converting lutein 3′-alkyl ether to a mixture of anhydroluteins in the presence of an alcohol or mixture of alcohols with a catalytic amount of an aqueous mineral acid or an organic acid at a temperature between about 78° C. and about 100° C.  
   
   
       21 . A process for converting a mixture of anhydroluteins to β-cryptoxanthin and α-cryptoxanthin by heterogeneous catalytic hydrogenation, comprising reacting the anhydroluteins with hydrogen in the presence of a catalyst selected from transition elements of group VIII in an organic solvent to obtain a mixture of β-cryptoxanthin as the major product and α-cryptoxanthin as the minor product.  
   
   
       22 . The process of  claim 21 , wherein said mixture of anhydroluteins is rich in anhydrolutein III.  
   
   
       23 . The process of  claim 21 , wherein said mixture of anhydroluteins is prepared from lutein esters via lutein 3-acylesters 3′-alkyl ether or lutein 3′-alkyl ether.  
   
   
       24 . The process of  claim 21 , wherein said organic solvent is selected from group consisting of ethyl acetate, acetone, tetrahydrofuran (THF), diethyl ether, diisopropyl ether or tert-butyl methyl ether, dichloromethane, 1,2-dichloroethane and chloroform, or their combination.  
   
   
       25 . A process for converting a mixture of anhydroluteins containing minor quantities of zeaxanthin to β-cryptoxanthin and α-cryptoxanthin by homogeneous catalytic hydrogenation, comprising reacting the anhydroluteins with hydrogen in the presence of a catalyst selected from transition metal complexes in an organic solvent at temperatures less than about 60° C. to obtain a mixture of β-cryptoxanthin and α-cryptoxanthin.  
   
   
       26 . The process of  claim 25 , wherein the transition metal complexes are selected from the group consisting of palladium acetylacetonate, tris(triphenylphosphine)rhodium (I) chloride [Rh(Ph 3 P) 3 Cl] (Wilkinson's catalyst), (tricyclohexylphosphine)(1,5-cyclooctadiene)pyridine Iridium (I) hexafluorophosphate [(C 6 H 11 ) 3 P[C 8 H 12 ][C 5 H 5 N]Pr +  PF6 −  (Crabtree catalyst), and (1,5-cyclooctadiene)bis(methyldiphenylphosphine) Iridium (I) hexafluorophosphate [C 8 H 12 ][(MePh 2 P) 2 ]Ir + PF6 − .  
   
   
       27 . The process of  claim 25 , wherein said mixture of anhydroluteins I-III is rich in anhydrolutein III.  
   
   
       28 . The process of  claim 25 , wherein said organic solvent is selected from the group consisting of ethyl acetate, acetone, tetrahydrofuran (THF), diethyl ether, diisopropyl ether or tert-butyl methyl ether, dichloromethane, 1,2-dichloroethane and chloroform, or their combination.  
   
   
       29 . A composition of matter comprising the product of the process of claims  5 .  
   
   
       30 . A composition of matter comprising the product of the process of claims  9 .  
   
   
       31 . A composition of matter comprising the product of the process of claims  13 .  
   
   
       32 . A composition of matter comprising the product of the process of claims  21 .  
   
   
       33 . A composition of matter comprising the product of the process of claims  25 .  
   
   
       34 . A process for converting a lutein product into β- and α-cryptoxanthin, comprising the steps of converting the product to a mixture of anhydroluteins using acid-catalysis, and converting the anhydroluteins to β- and α-cryptoxanthin using catalytic hydrogenation wherein the lutein-products are selected from the group consisting of lutein, lutein esters, anhydroluteins, and combinations of such products.  
   
   
       35 . A composition of matter comprising the product of the process of  claim 34.