Synthesis, absolute configuration and conformation of the aldose reductase inhibitor sorbinil

Abstract

The aldose reductase inhibitor 2,3-dihydro-6-fluorospiro[4H-1-benzopyran-4,4''-imidazolidine]-2'',5''-dione was resolved into its enantiomers. Sorbinil, the S isomer, was found to be a better inhibitor of the enzyme in vitro and in vivo than the corresponding R isomer. X-ray data on sorbinil, which were used to determine its absolute configuration, are presented. NMR studies of sorbinil in solution indicate the existence of two conformers with a low energy barrier for interconversion.