Total synthesis of apoptolidin: construction of enantiomerically pure fragments.
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.
Nicolaou
K C
KC
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
Fylaktakidou
Konstantina C
KC
Monenschein
Holger
H
Li
Yiwei
Y
Weyershausen
Bernd
B
Mitchell
Helen J
HJ
Wei
Heng-xu
HX
Guntupalli
Prasuna
P
Hepworth
David
D
Sugita
Kazuyuki
K
D018942:Macrolides / Q000138:chemical synthesis*; D013237:Stereoisomerism
D018942:Macrolides; C114125:apoptolidin