Synthesis of Key Fragments of Amphidinolide Q — A Cytotoxic 12-membered Macrolide

Abstract

b-Hydroxy aldehyde and alkyl ketone moieties were effectively synthesized as key intermediates of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp.. The asymmetric center of the former derivative was produced by Sharpless asymmetric epoxidation, followed by E-selective 1,4-addition to give the sp2 methyl group. Derivatization of the L-ascorbic acid derivative by Evans asymmetric alkylation and Peterson olefination provided the latter intermediate. The coupling reaction of the segments was examined.

Keywords

• amphidinolide Q
• Amphidinium sp.
• macrolide synthesis
• cytotoxic marine natural product