FACILE BIOCATALYTIC REDUCTION OF THE CARBON-CARBON DOUBLE-BOND OF 5-BENZYLIDENETHIAZOLIDINE-2,4-DIONES - SYNTHESIS OF (+ 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 do uble bonds in 5-benzylidenethiazolidine-2,4-diones, to give the corres ponding 5-benzylthiazolidin-2,4-diones, using whole cells of red yeast s is described. These reduced compounds, which are recovered in good y ield, are of potential use in the treatment of non-insulin dependent d iabetes mellitus. The mild reaction conditions developed allow reducti on of 5-benzylidenethiazolidine-2,4-diones containing other functional ities which are not compatible with alternative reduction methods. The biocatalytic reduction is enantioselective and the synthesis of pyrid yl)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 th ese whole cell reduction systems is described.