Zeaxanthin absolute configuration

Stereochemistry.—Carotenoids. The absolute configuration of astaxanthin [3,3 -dihydroxy-/3,/3-carotene-4,4 -dione (33)] has been determined21 as (3S,3 S) by c.d. correlation of the tetrol (34) obtained by LiAlH4 reduction of astaxanthin diester (from lobster) with (37 ,3. R)-zeaxanthin (7). The astaxanthin thus cannot exist in vivo as a bis-dianion, e.g. (35), bound to protein, since chirality could not be introduced by solvent extraction. Actinioerythrin [3,3 -dihydroxy-2,2 -dinor-/3,/3-carotene-4,4 -dione 3,3 -diacylate (36)] is also optically active, with the two end-groups having the same (undetermined) chirality. The (3S,3 S) chirality has also been demonstrated for astaxanthin from the spider mite Schizonobia sycophanta.22... 

The absolute configuration of natural zeaxanthin (119) was clearly shown to be (37 ,3 7 ) [30,31]. The first total synthesis of (37 ,3 / )-zeaxanthin (119) was reported in 1975 [32]. Later, additional routes have been worked out, which also made the (35,3 5)-enantiomer and the (3/ ,3 5)-m 5(9-compound readily available [33,34]. More recently, technically feasible syntheses have been reported [35,36]. The preparation of various fZ)-isomers of (3/ ,3 7 )-zeaxanthin (119) has also been published [37]. 

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. 

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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