SYNTHETIC STUDIES ON THE POLYENE MACROLIDE ANTIBIOTICS - DEVELOPMENT OF SYN-1,3-DIOL AND ANTI-1,3-DIOL SUBUNITS AND ASSEMBLY OF THE POLYACETATE REGION OF AMPHOTERICIN-B

The synthesis of syn- and anti-1,3-diol subunits from thiol ester oxaz oline 4 has been described. The key features of these synthetic sequen ces include the stereodivergent allylation of an asymmetric beta-amino aldehyde (7) and the stereospecific transformation of a vicinal amino alcohol to an epoxide. The resultant diasteromeric silyl-protected ep oxy alcohols (10s and 10a) serve as convenient precursors to the isome ric diol aldehyde derivatives 13, 13-ent, and 16. One of these fragmen ts, compound 13, has been exploited in a highly convergent synthesis o f the C1-C13 polyacetate segment of amphotericin B.