Enantioselective total synthesis of (-)-taxol

Enantioselective total synthesis of taxol has been accomplished. Coupling r eaction of the optically pure A-ring hydroxy aldehyde with the aromatic C-r ing fragment followed by Lewis acid mediated eight-membered B-ring cyclizat ion gave the desired ABC endo-tricarbocycle. The C-ring moiety of this prod uct was reduced under Birch conditions to the cyclohexadiene derivative, wh ich was oxygenated by singlet oxygen from the convex beta-face to give the C4 beta,C7 beta-diol stereoselectively. For introduction of the C19-methyl, the cyclopropyl ketone was prepared via cydopropanation of the C-ring ally lic alcohol or conjugate addition of a cyano group to the C-ring enone. Red uctive cleavage of the cyclopropane ring followed by isomerization of the r esulting enol to the corresponding ketone gave the crucial synthetic interm ediate containing the C19-methyl group. Regioselective transformation of th ree hydroxyl groups of this intermediate, conversion of the C4-carbonyl gro up to the allyl chloride, and introduction of the C10-oxygen functionality afforded a precursor for D-ring construction. Dihydroxylation of the allyl chloride moiety followed by basic treatment of the resulting diol gave a fu lly functionalized taxol skeleton. Functional group manipulation of this pr oduct including attachment of the C13 side chain provided (-)-taxol.