TOTAL SYNTHESIS OF TAXOL .1. RETROSYNTHESIS, DEGRADATION, AND RECONSTITUTION

A successful strategy for the enantioselective synthesis of the natural stereoisomer of Taxol (1) has been developed. This strategy utilized the convergent assembly of Taxol's central eight-membered B ring from preformed synthons for rings A (10) and C (9) followed by late introduction of the D ring and side chain. Degradative studies confirmed the viability of certain crucial manipulations including oxidation of the C13 position (35 --> 3) and regioselective introduction of the C1-hydroxyl, C2-benzoyloxy moiety (29 --> 31). Additionally, a convenient method for the large-scale production of 29, a derivative useful for C2 analog production, was developed.