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Communication | Regular issue | Vol 36, No. 1, 1993, pp.13-20
Published online, 1st January, 1970
DOI: 10.3987/COM-92-6177
■ Studies with Plant Cell Culture of Podophyllum peltatum L. II. Biotransformation of Dibenzylbutanolides to Lignans. Development of a "Biological Factory" for Lignan Synthesis

James P. Kutney,* Yung Ping Chen, Shixiang Gao, Gary M. Hewitt, Francisco Kuri-Brena, Radka K. Milanova, and Nikolay M. Stoynov

*Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B.C. V6T 1Z1, Canada

Abstract

An efficient and versatile synthetic route to appropriate dibenzylbutanolides suitable for biotransformation to lignans as potentila intermediates for the syntheses of the clinical anti-cancer drug etoposide has been developed. Biotransformation of such substrates, for example 10, with cell cultures of Podophyllum peltatum affords a potentially exciting route to this drug. Of particular significance is the development of a semi-continuous fermentation process with these plant cells wherein successive additions of substrate and isolation of end products can be pursued with a given batch of cells and over a period of several months. Biotransformation times for the conversion of 10 to 11 and 12 are short (usually 24-48 h). Although conditions have not yet optimized, this "biological factory" for lignan synthesis provides a novel approach for the use of plant cells, in combination with chemistry, for continuous and large scale production of such metabolites.