160147-03-5Relevant articles and documents
Enantioselective total synthesis of (-)-taxol
Kusama, Hiroyuki,Hara, Ryoma,Kawahara, Shigeru,Nishimori, Toshiyuki,Kashima, Hajime,Nakamura, Nobuhito,Morihira, Koichiro,Kuwajima, Isao
, p. 3811 - 3820 (2007/10/03)
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.
