Total Synthesis of Rhizoxin D

Abstract

A total synthesis of rhizoxin D (1b), a 16-membered antitumoral macrolide, is reported. The strategy relies on the application of a Brown allylation reaction for the C 15 and C 16 asymmetric centres control. Installation of the C17 hydroxyl function with concomitant building of the (E)-C18-C19 double bond was effected by a diastereoselective addition of vinyllithium derivative 15 to aldehyde 10. The terminal enone group was then introduced to achieve the preparation of C11-C20 segment 23. A Heck coupling reaction between C11-C20 fragment 23 and C3-C10 segment 24 (previously prepared in our laboratory) was performed with success to deliver the C3-C20 fragment 25. The total synthesis of rhizoxin D (1b) was achieved after transformation of 25 into the macrolactone 28, and coupling the C21-C28 side chain using a Wittig-Wadsworth-Emmons reaction.