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

A novel biotransformation system for the reduction of carbon-carbon double bonds in 5-benzylidenethiazolidine-2,4-diones, to give the corresponding 5-benzylthiazolidin-2,4-diones, using whole cells of red yeasts is described. These reduced compounds, 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 reduction of 5-benzylidenethiazolidine-2,4-diones containing other functionalities which are not compatible with alternative reduction methods. The biocatalytic reduction 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 crystallography is detailed. Optimisation of reaction conditions (including immobilisation) for these whole cell reduction systems is described.