Total synthesis of amphoteronolide B and amphotericin B. 1. Strategy and stereocontrolled construction of key building blocks

The retrosynthetic analysis and strategy for the total synthesis of amphotericin B (1) and amphoteronolide B (2) is discussed. Focusing on subtle and repeated structural units, a retrosynthetic scheme was constructed that led to the recognition of readily available and enantiomerically related compounds as starting materials for the total synthesis of 1 and 2. Thus, the four key building blocks 8-11 were defined as subtargets and synthesized in optically active forms. Segments 8 and 11 were derived from epoxide 15, which is readily available from (+)-DET. Segments 9 and 10 were obtained from (+)- and (-)-xylose, respectively, or from the prostereogenic allylic alcohol 14 and (-)- and (+)-DET. respectively, via a stereocontrolled sequence based on the Sharpless asymmetric epoxidation reaction. This latter sequence provides a general and flexible entry into the 1,3,5,...(2n + 1) polyol series of compounds, reminiscent of substructures occurring in polyene macrolide antibiotics.