1998/12/01 by Koichiro Morihira, Ryoma Hara, Shigeru Kawahara +4 · 7 citations
Medicine · Chemistry · Biochemistry, Genetics and Molecular Biology · #Cancer Treatment and Pharmacology #Synthetic Organic Chemistry Methods #Microtubule and mitosis dynamics
paper · doi:10.1021/ja9824932
openalex publication_date 1998/12/01 · 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\npure 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\nwas reduced under Birch conditions to the cyclohexadiene derivative, which was oxygenated by singlet oxygen\nfrom the convex β-face to give the C4β,C7β-diol stereoselectively. For introduction of the C19-methyl, the\ncyclopropyl ketone was prepared via cyclopropanation of the C-ring allylic alcohol or conjugate addition of\na cyano group to the C-ring enone. Reductive cleavage of the cyclopropane ring followed by isomerization of\nthe 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\nC4-carbonyl group to the allyl chloride, and introduction of the C10-oxygen functionality afforded a precursor\nfor D-ring construction. Dihydroxylation of the allyl chloride moiety followed by basic treatment of the resulting\ndiol gave a fully functionalized taxol skeleton. Functional group manipulation of this product including\nattachment of the C13 side chain provided (−)-taxol.