Total synthesis of peridinin and related C37-norcarotenoid butenolides

Abstract

As an extension of our synthesis of symmetrical carotenoids, the preparation of the highly functionalized C37-norcarotenoid butenolide peridinin (1), its 6'-epi- and 11'Z stereoisomers has been completed. Featuring a central dihalogenated C8 linchpin unit 6, two synthetic routes, differing in the ordering of the last three steps were explored by using the C3,C3'-bisdehydroxylated target as the model system. The first route uses the combination of a modified Z-selective Julia reaction and two sequential Stille couplings, the last one producing the isomerisation of the polyene Z double bond. The second route inverts these steps and makes the isolation of the 11'Z stereoisomers as major products possible. An efficient Z to E isomerisation of the final carotenoid skeleton simply uses the Stille reaction conditions at ambient temperature. As the reaction of bromoallene 12 with alkenylstannane 11 occurs with inversion of configuration, 6'-epi-peridinin could also be prepared by route A. The advantages and limitations of the sequential Stille cross-coupling approach to carotenoids are highlighted.