Total synthesis of epothilone E and related side-chain modified analogues via a Stille coupling based strategy

A Stille coupling strategy has been utilized to complete a total synthesis of epothilone E from vinyl iodide 7 and thiazole stannane 8h. The central c ore fragment 7 and its trans-isomer 11 were prepared from triene 15 using r ing-closing metathesis (RCM), and were subsequently coupled to a variety of alternative stannanes to provide a library of epothilone analogues 18a-o a nd 19a-o. The Stille coupling approach was then used to prepare epothilone B analogues from the key macrolactone intermediate 24 which was itself synt hesized by a macrolactonization based strategy. (C) 1999 Elsevier Science L td. All rights reserved.