Lutein absolute configuration

Isbell, A.R, Berry, J.P., and Tansey, L.W.. Amino phosphonic acids. Part 3. The synthesis and properties of 2-aminoethylphosphonic and 3-aminopropylphosphonic acids, J. Org. Chem.. 37. 4399. 1972. Deschamps, B., Lefebvre, G., and Seyden-Penne, J., Mechanism of Homer-Emmons reaction. Part 1. Reaction of benzaldehyde and phosphonomtriles in tetrahydrofuran. Tetrahedron. 28. 4209. 1972. Buchecker, R., Hamm, P., and Eugster. C.H.. Absolute configuration of xanthphyll (lutein). Helv. Chim. Acta, 57, 631, 1974. 

In the carotenoid and polyterpenoid field a number of important stereochemical studies have appeared. These include assignments of the complete stereochemistry of phytoene" and lutein ° and the absolute configurations of absicic acid and the natural irones. ... 

In 1980 (3R,3 R,6 R)-lutein (133) was synthesized [24] in order to make available larger amounts of pure material for various investigations and also to explore routes for the synthesis of other lutein diastereoisomers [25]. This synthesis requires the controlled generation of chiral centres of defined absolute configuration and is outlined in Scheme 6. 

The chirality of lutein (14) is now firmly established with the 3,3 -hydroxy functions in the P- and s-rings possessing opposite absolute configuration 4, 40). The stereochemistry of the hydroxylation step in zeaxanthin (26) biosynthesis in a Flavobacterium sp. has been determined by using (5/ )-[2- C, 5- Hi] mevalonate as substrate which demonstrated retention of the 5-pro-S hydrogen at C-3(3 ) (50), Scheme 9. Also in the case of lutein (14) it has been shown that the 5-pro-S hydrogen at C-3 is retained (81,171) and P,e-carotene (92) biosynthesized from (4/ )-[2- C, 4- Hi] mevalonate retains the tritium at C-6 (82). Any mechanistic interpretation of the biosynthetic evidence must be consistent with the established chirality. 

For instance, it has been claimed on the basis of isotopic labelling experiments that lutein (14) was converted to (3S,3 5)-astaxanthin (28) in fish (95, 111, 112). The route proposed which did not involve an epi-merization at C-3 is not compatible with the absolute configurations later established for (14) and (28). However, recent evidence for the 3 -S chirality of a-doradexanthin (96) from goldfish (43 a) has led to the plausible suggestion that the biosynthetic conversion of lutein (14) proceeds via 3 -didehydrolutein- (3 5 )-epilutein (58)- (3 S)-oc-doradexanthin (96) - (3S,3 5)-astaxanthin (28). The reported conversion of alloxanthin (31) to 7,8,7, 8 -tetradehydroastaxanthin (34) in goldfish (55) is compatible with stereochemical data. But this would also be true for a conversion of (3S,3 S)-astaxanthin (28) to its 7,8,7, 8 -tetra-dehydroderivative (28). 

Andrewes, a. G., G. Borch, and S. Liaaen-Jensen On the absolute configuration of lutein. Acta Chem. Scand. B28, 139 (1974). 

The biosynthetic results of Goodwin and co-workers using [2- C,31 ,5K- H]-mevalonic acid show that hydroxylation at C-3 results in the loss of tritium when zeaxanthin (6) or jS-cryptoxanthin is formed. Since the absolute stereochemistry of the tritium atom at C-3 is known before hydroxylation this result confirms that there is retention of configuration. Assuming retention on hydroxylation to give lutein (7) the loss of tritium from both positions in its biosynthesis suggests the absolute stereochemistry indicated at C-3 and C-3. ... 

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