ANALYSIS OF WARFARIN ENANTIOMERS - CHROMATOGRAPHIC-SEPARATION OF 6 STEREOISOMERIC ESTERS PREPARED FROM ,7-HEXACHLOROBICYCLO[2,2,1]HEPT-5-ENE-2-CARBOXYLIC ACID

Reaction of rac-warfarin, (-)-(1S, 2R, 4R)-endo-1, 4, 5, 6, 7, 7-hexac hlorobicyclo[2.2.1]hept-5-ene-2-carboxylic acid [(-)-HCA] and carbodii mide reagents gave two noncyclic ketonic diastereoisomeric derivatives whereas rac-warfarin and (-)-HCA acid chloride with 4-(dimethylamino) pyridine gave four cyclic hemiketal diastereoisomeric ester derivative s, The structure and stereochemistry of diastereoisomeric esters prepa red from warfarin and p-chlorowarfarin were determined from H-1- and C -13-NMR spectra, mass spectra, and hydrolysis to warfarin and p-chloro warfarin enantiomers, The structure and stereochemistry of one of the cyclic hemiketal diastereoisomeric derivatives of warfarin are support ed by an X-ray crystallographic determination, Mechanisms for the form ation of all products are proposed. (C) 1994 Wiley-Liss, Inc.