Total synthesis of lycopene-5,6-diol and γ-carotene-5′,6′-diol stereoisomers and their HPLC separation

Abstract

Lycopene-5,6-diol stereoisomers (1a,b) and (2a,b) and γ-carotene-5′,6′-diol stereoisomers (3a,b) and (4a,b) were synthesized by a stepwise C15 + C10 + C15 double Wittig reaction strategy. The key compounds erythro(anti)-C15-dihydroxy aldehydes 17a,b and their threo(syn)-stereoisomers 23a,b were prepared via Sharpless asymmetric epoxidation of geraniol and nerol followed by acidic hydrolysis of the epoxides in a stereospecific manner. The enantiomerically enriched anti-isomers were obtained by way of recrystallization of 2,3-epoxygeranyl 3,5-dinitrobenzoates 9a,b, whereas syn-isomers were obtained as enantiomerically pure forms via recrystallization of dihydroxyneryl 3,5-dinitrobenzoates 21a,b. In order to determine the absolute stereochemistry of natural products, HPLC separation methods for each enantiomers 1a,b–4a,b were established by using a column carrying a chiral stationary phase.