title: Scalable enantioselective total synthesis of taxanes.
abstract: Taxanes form a large family of terpenes comprising over 350 members, the most famous of which is Taxol (paclitaxel), a billion-dollar anticancer drug. Here, we describe the first practical and scalable synthetic entry to these natural products via a concise preparation of (+)-taxa-4(5),11(12)-dien-2-one, which has a suitable functional handle with which to access more oxidized members of its family. This route enables a gram-scale preparation of the 'parent' taxane--taxadiene--which is the largest quantity of this naturally occurring terpene ever isolated or prepared in pure form. The characteristic 6-8-6 tricyclic system of the taxane family, containing a bridgehead alkene, is forged via a vicinal difunctionalization/Diels-Alder strategy. Asymmetry is introduced by means of an enantioselective conjugate addition that forms an all-carbon quaternary centre, from which all other stereocentres are fixed through substrate control. This study lays a critical foundation for a planned access to minimally oxidized taxane analogues and a scalable laboratory preparation of Taxol itself.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Mendoza
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000475:Alkenes; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D043823:Taxoids; C093125:taxa-4(5),11(12)diene