Asymmetric synthesis and determination of the absolute configuration of FK584, an agent for the treatment of overactive detrusor

FK584 [(-)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride, (- )-4 . HCl], a potential candidate for the treatment of overactive detrusor, was synthesized in a 4-step approach starting with Sharpless oxidation of cyclopentenol 6 (kinetic resolution). This epoxidation is a rare case in th at the empirical rule does not work. Regio- and stereoselective introductio n of tert-butylamine to the obtained epoxycyclopentanol 5 and subsequent co nversion of the resulting diol to an olefin completed the synthesis. The ab solute configuration of FK584 was determined to be S by X-ray crystallograp hic analysis of the salt of S-(+)-mandelic acid.