Formal Synthesis of Palmerolide A, Featuring Alkynogenic Fragmentation and syn-Selective Vinylogous Aldol Chemistry

An enantioselective route to palmerolide A is described. The approach features original syntheses of three subunits, which are then assembled to produce a known late-stage intermediate and formally provide the highest overall yield of the natural product reported to date. Recent innovations in alkynogenic fragmentation and vinylogous aldol methodology figure prominently in the synthesis of the C1-C15 and C16-C25 subunits, respectively.