Facile biocatalytic reduction of the carbon-carbon double bond of 5-benzylidenethiazolidine-2,4-diones. Synthesis of ( )-5-(4-{2-[methyl(2-pyridyl)amino]ethoxy}benzyl)thiazolidine-2,4-dione (BRL 49653), its (R)-(+)-enantiomer and analogs.

Cantello, Barrier C. C.; Eggleston, Drake S.; Haigh, David; Haltiwanger, R. Curtis; Heath, Catherine M.; Hindley, Richard M.; Jennings, Keith R.; Sime, John T.; Woroniecki, Stefan R. SmithKline Beecham Pharmaceuticals, Surrey, UK. Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1994), (22), 3319-24. Publisher: Royal Society of Chemistry, CODEN: JCPRB4 ISSN: 0300-922X. Journal written in English. CAN 122:105736 AN 1995:237497 CAPLUS (Copyright (C) 2009 ACS on SciFinder (R)) Abstract A novel biotransformation system for the redn. of carbon-carbon double bonds in 5-benzylidenethiazolidine-2,4-diones to give the corresponding 5-benzylthiazolidine-1,4-diones, using whole cells of red yeasts, is described. These reduced compds., which are recovered in good yield, are of potential use in the treatment of non-insulin dependent diabetes mellitus. The mild reaction conditions developed allow redn. of 5-benzylidenethiazolidine-2,4-diones contg. other functionalities which are not compatible with alternative redn. methods. The biocatalytic redn. is enantioselective and the synthesis of R-(+)-5-(4-{2-[methyl(2-pyridyl)amino]ethoxy}benzyl)thiazolidine-2,4-dione by Rhodotorula rubra CBS 6469 and structure confirmation by X-ray crystallog. is detailed. Optimization of reaction conditions (including immobilization) for these whole cell redn. system is described.