Process for the preparation of meso-zeaxanthine

摘要

Preparation of meso-zeaxanthin (A) involves separating a racemic mixture of 1-ethynyl-2,2,6-trimethyl-cyclohexane-1,4-diols (I) into the R- and S-antipodes, then converting them into sterically uniform (A) by four further stages including two Wittig reactions. Several classes of intermediate compounds are new. Preparation of meso-zeaxanthin of formula (A) involves: (a) separating a racemic mixture of acetylenic diols of formulae R-(I) and S-(I) into its antipodes; (b) converting R-(I) and S-(I) into the corresponding 15C phosphonium salts of formulae R-(II) and S-(II) respectively; (c) subjecting R-(II) or S-(II) to Wittig reaction with a 10C dial monoacetal of formula (III), to give a 25C acetal of formula R-(IV) or S-(IV); (d) converting R-(IV) or S-(IV) into the 25C aldehyde of formula R-(V) or S-(V) respectively; and (e) subjecting R-(V) and S-(II) or S-(V) and R-(II) to Wittig reaction to give sterically uniform (A). Ar = aryl; X = 1 equivalent of an anion of an (in)organic acid; R1, R2 = 1-8C alkyl, or R1 + R2 = CH2CR3R4CH2 or CHR5CH2, and R3-R5 = H or 1-4C alkyl. Independent claims are also included for: (i) the production of optically pure R-(I) and S-(I), by conversion of a racemic mixture of R-(I) and S-(I) into a diastereomer mixture using an optically active auxiliary reagent (AR), separating the diastereomers and cleaving AR, and (ii) S-(I), protected S-(I) derivatives of formula S-(XI), cyclohexane derivatives of formulae R-(VI) and S-(VI) and acetylene compounds of formula S-(VII) as new compounds. R6 = optically active urethane, carbonate, sulfonate or acyl residue; R7 = H, 1-12C acyl or a hydrolytically cleavable acetal or ether protecting group; R8 = H or C(Me)(OR9)-CH-CH2; R9 = H or Li, and R10 = non-chiral 1-12C acyl or a hydrolytically cleavable acetal or ether protecting group.