title: Total synthesis of apoptolidin: construction of enantiomerically pure fragments.
abstract: A general strategy for the total synthesis of the antitumor agent apoptolidin (1) is proposed, and the chemical synthesis of the defined key building blocks (4, 5, 6, 8, and 9) in their enantiomerically pure forms is described. The projected total synthesis calls for a dithiane coupling reaction to construct the C(20)-C(21) bond, a Stille coupling reaction to form the C(11)-C(12) bond, and a Yamaguchi macrolactonization to assemble the macrolide ring, as well as two glycosidation reactions to fuse the carbohydrate units onto the molecule. First and second generation syntheses to the required fragments for apoptolidin (1) are described.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. kcn@scripps.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.forename: Konstantina C
authors.initials: KC
authors.lastname: Fylaktakidou
authors.forename: Holger
authors.initials: H
authors.lastname: Monenschein
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
authors.forename: Bernd
authors.initials: B
authors.lastname: Weyershausen
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mitchell
authors.forename: Heng-xu
authors.initials: HX
authors.lastname: Wei
authors.forename: Prasuna
authors.initials: P
authors.lastname: Guntupalli
authors.forename: David
authors.initials: D
authors.lastname: Hepworth
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugita
mesh_terms: D018942:Macrolides / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D018942:Macrolides; C114125:apoptolidin