Chemistry of A83543A Derivatives. 1. Oxidations and Reductions of A83543A Aglycon

A retro-biomimetic degradation of the A83543 tetracyclic ring system was investigated as one approach to obtaining putative polypetide-derived, late-stage biosynthetic precursors for the subsequent study of their cyclizations. However, initial studies revealed an unexpected chemical stability of the ring system that required the development of indirect methods to cleave the ring-forming bonds. Hydride reagents were espe- cially useful for reductively cleaving the lactone and generating novel derivatives, whose structures and stereochemistries were determined by detailed NMR analyses correlated with results from molecular modeling. The latter were also used to rationalize the conformational behaviors and lack of reactivities exhibited by the macrocyclic lactone systems in the parent and 13,14-enone-reduced derivatives