Total synthesis of apoptolidin: construction of enantiomerically pure fragments

K C Nicolaou; Konstantina C Fylaktakidou; Holger Monenschein; Yiwei Li; Bernd Weyershausen; Helen J Mitchell; Heng-xu Wei; Prasuna Guntupalli; David Hepworth; Kazuyuki Sugita

doi:10.1021/ja0304953

Total synthesis of apoptolidin: construction of enantiomerically pure fragments

J Am Chem Soc. 2003 Dec 17;125(50):15433-42. doi: 10.1021/ja0304953.

Authors

K C Nicolaou¹, Konstantina C Fylaktakidou, Holger Monenschein, Yiwei Li, Bernd Weyershausen, Helen J Mitchell, Heng-xu Wei, Prasuna Guntupalli, David Hepworth, Kazuyuki Sugita

Affiliation

¹ 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

PMID: 14664589
DOI: 10.1021/ja0304953

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Macrolides / chemical synthesis*
Stereoisomerism

Substances

Macrolides
apoptolidin