Asymmetric Total Synthesis of Taxol

摘要

The asymmetric total synthesis of Taxol was achieved by way of B to BC to ABC to ABCD ring construction. Optically active 8-membered ring enones 1 and 2 corresponding to the B ring of Taxol have been synthesized in high yields from thelinear precursors 28 and 32, respectively, by intramolecular aldol cyclization using SmI_2. The optically active linear polyoxy compounds 28 and 32 were obtained by way of diastereoselective aldol reaction between aldehyde 4 and ketene silyl acetal 8 catalyzed by MgBr_2 centre dot OEt_2. The chiral pentanal 4 was synthesized either by asymmetric aldol reactionof achiral aldehyde 7 and ketene silyl acetal 8 by means of a chiral Laewis acid or by diasteroselective aldol reaction between the chiral aldehyde 16, derived from L-serine, and thelithium enolate derived from methyl isobutyrate. Optically active bicyclo[6.4.0]dodecaone 38#beta#, corresponding to the BC ring system of Taxol, was prepared from 8-membered ring enone 2 in high yield by stereoselective Michael addition and successive intramolecular aldol cyclization. Furthermore, baccatin III, the ABCD ring system of Taxol, was efficiently synthesized from the BC ring system 38#beta# by successive construction of the A and D rings by intramolecular pinacol coupling cyclization, introduction of the C-13 hydroxyl group and an oxetane-forming reaction. Finally, the total synthesis of Taxol was accomplished by dehydration condensation between a protected N-benzoylphenylphenylisoserine 70 or 75 and 7-TES baccatin III, prepared from baccatin III. Taxol side chains 70,73,75, and 77, optically active protected N-benzoylphenylioserines, were synthesized by enantioselective aldol reaction from two achiral sarting materials, bezldehydr and an enol silyl ether 65 derived from S-ethyl benzyloxyethanethioate.