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Synthesis 2002(7): 0888-0894
DOI: 10.1055/s-2002-28510
PAPER
© Georg Thieme Verlag Stuttgart · New York

Toward a Total Synthesis of Okilactomycin. 1. A Direct, Enantiocontrolled Route to the Western Sector

Leo A. Paquette*, Serge L. Boulet
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA
Fax: +1(614)2921685; e-Mail: paquette.1@osu.edu;
Further Information

Publication History

Received 19 November 2001
Publication Date:
14 May 2002 (online)

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Abstract

A synthesis of the western half of the macrocyclic ring framework of the antitumor antibiotic okilactomycin is described. The strategy employed rests on an efficient synthesis of meso-2,4-dimethylglutaric anhydride and ensuing resolution via reaction with (S)-(-)-α-methylbenzylamine, diborane reduction, and selective crystallization. Following acid-catalyzed cyclization to (2S,4R)-2,4-dimethyl-δ-valerolactone, an acyclic stereocontrol strategy was adopted to achieve chain lengthening with appropriate incorporation of functionality. The sensitive aldehyde 2 was further homologated to β-keto ester 17 in a model reaction sequence performed to simulate its ultimate projected coupling to 3.

Key words

anhydride - resolution - epoxidation - dithiane - oxidation

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