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(Ph3P)3Cl (Wilkinson's catalyst), [(C6H11)3P[C8H12][C5H5N]Ir+PF6− (Crabtree catalyst), or [C8H12][(MePh2P)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.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of Invention [0002] The invention is in the field of organic chemistry. The invention relates to a process that converts a mixture of dehydration products of (3R,3′R,6′R)-lutein, hereto after referred to as anhydroluteins, to a mixture of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin by catalytic hydrogenation with a variety of heterogeneous and homogeneous catalysts under mild conditions at atmospheric pressure. Two alternative processes have also been developed that can convert unesterified lutein to anhydroluteins. The invention also relates to a process that converts other lutein sources to anhydroluteins. [0003] 2. Background of the Art [0004]β-Cryptoxanthin, as measured through blood plasma samples, is associated with blood pressure reduction as seen in an Oxford University large intervention trial (John J H, Ziebland S, Yudkin P, Roe L S, Neil H A. Effects of fruit and vegetable consumption on plasma antioxidant concentrations a...

AI Technical Summary

Benefits of technology

[0010] In an attempt to eliminate the use of chlorinated solvents and reagents that may be toxic to humans, an alternative process for the second step of the partial synthesis of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin from anhydroluteins has been developed. This has been accomplished by heterogeneous or homogeneous catalytic hydrogenation of anhydroluteins. Catalytic hydrogenation has been extensively used in pharmaceutical and food industries and offers an economical route to products that can be safely used by humans. There are numerous literature examples that deal with heterogeneous and homogeneous hydrogenation of cycloalkenes and cyclodienes (H. Takaya, R. Noyori in Comprehensive Organic Synthesis, Eds. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, Vol 8, pp 417-470). However, to date, there are no literature reports on regioselective catalytic hydrogenation of carotenoids. This is primarily due to the presence of a highly conjugated polyene chain in carotenoids that makes these compounds readily susceptible to hydrogenation and as a result the regioselectivity of this process is difficult to control. Nonetheless, the present invention will demonstrate that under carefully controlled conditions, hetereogeous and homogeneous catalytic hydrogenation of anhydroluteins with a wide range of catalysts in various solvents can yield a mixture of (3R)-β-cryptoxanthin and (3R,6′R)-x-cryptoxanthin in moderate to excellent selectivity and yields.

[0011] Therefore, in an alternative embodiment, the present invention converts anhydroluteins rich in anhydrolutein III to a mixture of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin by heterogeneous catalytic hydrogenation employing transition elements group VIII such as platinum, palladium, or rhodium supported on carbon or alumina at temperatures ranging from −15° C. to 40° C. in a variety of organic solvents. Among these catalysts, platinum supported on alumina provides the best yield of (3R)-β-cryptoxanthin and (3R,6′R)-α-cryptoxanthin.

[0014] The present invention also improves the process that converts lutein to anhydroluteins by reducing the volume of solvents and increasing the purity and stability of the products. In addition to the use of dry lutein powder as the starting material, the present invention further demonstrates that lutein-containing products with considerable amounts of water content, hereinafter referred to as wet lutein, can be employed to convert this carotenoid to anhydroluteins in excellent yields. Wet lutein, as used in this disclosure includes any lutein-containing product that includes more water than dry lutein-powder. Specifically included in the term wet lutein is the product produced as described in U.S. Pat. No. 5,648,564 at the point where water has been added to the saponified oleoresin and some of the liquid removed by centrifugation. Kemin Industries (Des Moines, Iowa) sells OroGLO® Liquid products that are also included in the term wet lutein.

[0015] (3R)-β-Cryptoxanthin and (3R,6′R)-α-cryptoxanthin can be used as dietary supplements, nutritional ingredients, or as a food coloring additives. The commercial availability of these carotenoids allows scientists to investigate the potential chemopreventive efficacy of these compounds as neuroprotectors and in the promotion of bone health as well as in the prevention of cancer, cardiovascular disease, and macular degeneration.

Problems solved by technology

However, to date, there are no literature reports on regioselective catalytic hydrogenation of carotenoids.

This is primarily due to the presence of a highly conjugated polyene chain in carotenoids that makes these compounds readily susceptible to hydrogenation and as a result the regioselectivity of this process is difficult to control.

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