ASYMMETRIC-SYNTHESIS OF A XANTHINE DEHYDROGENASE INHIBITOR (S)-(-)-BOP-4272 - UTILITY OF CHIRAL ALKOXYSULFONIUM SALTS

A practical synthetic method for a xanthine dehydrogenase inhibitor, ( S)-(-)-BOF-4272, was established utilizing an asymmetric oxidation of diaryl sulfide BOF-4269; The oxidation of the sulfide with 1-chloroben zotriazole carried out in the presence of 4-cyanopyridine and chiral 2 -phenylcyclohexanol gave a high enantiomeric excess (73%ee). The sulfo xides in each enantiomerically pure form could be obtained by treating with alkaline hydrolysis or thermolysis of one of the diastereomeric intermediate sulfonium salts (>99%de). Thus the transformation into th e sulfoxides occur with virtually perfect inversion (alkaline hydrolys is) or retention (thermolysis). It is therefore possible to obtain the target sulfoxide, (S)-(-)-BOF-4272, from both the two diastereomeric sulfonium intermediates.