2000/04/01 by Hiroyuki Kusama, Ryoma Hara, Shigeru Kawahara +5 · 8 citations
Medicine · Chemistry · #Cancer Treatment and Pharmacology #Synthetic Organic Chemistry Methods #Oxidative Organic Chemistry Reactions
paper · doi:10.1021/ja9939439
openalex publication_date 2000/04/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Enantioselective total synthesis of taxol has been accomplished. Coupling reaction of the optically pure A-ring hydroxy aldehyde with the aromatic C-ring fragment followed by Lewis acid mediated eight-membered B-ring cyclization gave the desired ABC endo-tricarbocycle. The C-ring moiety of this product was reduced under Birch conditions to the cyclohexadiene derivative, which was oxygenated by singlet oxygen from the convex β-face to give the C4β,C7β-diol stereoselectively. For introduction of the C19-methyl, the cyclopropyl ketone was prepared via cyclopropanation of the C-ring allylic alcohol or conjugate addition of a cyano group to the C-ring enone. Reductive cleavage of the cyclopropane ring followed by isomerization of the resulting enol to the corresponding ketone gave the crucial synthetic intermediate containing the C19-methyl group. Regioselective transformation of three hydroxyl groups of this intermediate, conversion of the C4-carbonyl group 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 fully functionalized taxol skeleton. Functional group manipulation of this product including attachment of the C13 side chain provided (−)-taxol.