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Synlett 2004(7): 1183-1186  
DOI: 10.1055/s-2004-825582
LETTER
© Georg Thieme Verlag Stuttgart · New York

Preparation of an Advanced Phenylglycine-Derived Intermediate en route to the Southern Hemisphere Tetraene of Viridenomycin

Graham N. Mawa, Carl Thirskb, Jean-Louis Toujasc, Michel Vaultierc, Andrew Whiting*b
a Pfizer Global Research & Development, Sandwich, Kent CT13 9NJ, UK
b Department of Chemistry, University Science Laboratories, South Road, Durham, DH1 3LE, UK
Fax: +44(191)3843747; e-Mail: andy.whiting@durham.ac.uk;
c Institut de Chimie de Rennes, Campus de Beaulieu, Avenue du Général Leclerc 35042 Rennes Cedex, France
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Publication History

Received 29 October 2003
Publication Date:
10 May 2004 (online)

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Abstract

A high-yielding synthesis of a phenylglycine derived (E,Z)-dienylboronate en route to the C16-C23 tetraene of the polyene macrolide viridenomycin is described. Crucial to this synthesis was the development of conditions enabling ready access to synthetically useful amino acid derivatives that should be widely applicable to other amino acids. These conditions confer advantages of increased yield and reliability over many of the existing literature alternatives, and also circumvent several of the problems encountered when dealing with such derivatives. The synthesis features a highly selective Heck coupling between an N-protected (Z)-alkenyl iodide and a hexylene glycol derived vinylboronate ester.

Key words

natural product - palladium - Heck reaction - asymmetric synthesis - amino alcohol

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