NEW AND EFFICIENT APPROACHES TO THE SEMISYNTHESIS OF TAXOL AND ITS C-13 SIDE-CHAIN ANALOGS BY MEANS OF BETA-LACTAM SYNTHON METHOD

Highly efficient chiral ester enolate-imine condensation giving 3-hydroxy-4-aryl-beta-lactams with excellent enantiomeric purity is successfully applied to the asymmetric synthesis of the enantiomerically pure taxol C-13 side chain, N-benzoyl-(2R,3S)-3-phenyl-isoserine and its analogs. (3R,4S)-N-benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetidinone readily derived from the 3-hydroxy-4-phenyl-beta-lactam is coupled with protected baccatin IIIs, followed by deprotection to give optically pure taxol and 10-deacetyl-7,10-bis(Troc)-taxol in good yields. Fully assigned H-1, C-13, and 2D (COSY and HETCOR) NMR spectra of taxol thus synthesized are shown and discussed.