Total synthesis of (+)-discodermolide: an improved endgame exploiting a Still-Gennari-type olefination with a C1-C8 beta-ketophosphonate fragment.

ABSTRACT

[structure see text] An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 101 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.