Total Synthesis of Pamamycin-649B

摘要: The first total synthesis of the macrodiolide antibiotic pamamycin-649B (1) was achieved by using sultone methodology. diethyl substituted larger hydroxy acid fragment constructed in a concise fashion through domino elimination/alkoxide-directed 1,6-additions ethyllithium to sultones derived from intramolecular Diels-Alder reaction furan-containing vinylsulfonates. Intermolecular Yamaguchi esterification two building blocks and subsequent cyclization eventually provided target macrocycle 1. Since final lactonization with formation ester linkage between C1' C8 oxygen proceeded complete C2' epimerization, more readily available epimeric smaller could be used streamline synthetic sequence.