Total synthesis of (-)-laulimalide.
(-)-Laulimalide (1), a structurally novel macrolide isolated in trace amounts from marine sponges, promotes abnormal tubulin polymerization and apoptosis in vitro, with a similar mode of action to that of Taxol(R), but with potentially less susceptibility to multidrug resistance. Herein, a flexible and convergent asymmetric synthesis of (-)-laulimalide is described. This synthesis featured a highly diastereoselective Sakurai reaction of 2 with 3 and a regioselective macrolactonization of an unprotected vicinal diol. Laulimalide was synthesized in 25 steps (longest linear; 36 overall) in 3.5% overall yield, providing a uniquely short and efficient route to 1 and its analogues.
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
Hegde
Sayee G
SG
Hubbard
Robert D
RD
Zhang
Lei
L
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D018942:Macrolides; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013237:Stereoisomerism; D043823:Taxoids
D000970:Antineoplastic Agents; D018942:Macrolides; D043823:Taxoids; C117305:laulimalide; D017239:Paclitaxel