Total Synthesis of the Antimitotic Marine Natural Product (+)-Curacin A.
The structurally novel antimitotic agent curacin A was prepared in 15 steps and in 2.6% yield for the longest linear sequence. Key steps in our synthesis are the use of a hydrozirconation-transmetalation protocol for the preparation of divinyl alcohol 8, the stereoselective formation of the acyclic triene segment 11 via enol triflate chemistry, and a second hydrozirconation of the conjugated triene followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A, the oxazoline --> thiazoline conversion offered an efficient access to the sensitive marine natural product.
Wipf
Peter
P
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
Xu
Wenjing
W