Abstract

PIP: The resolution of gossypol for the purpose of comparing the biologic action of (-)-gossypol with its naturally occurring antipode has attracted the attention of scientists. Recently the 1st successful resolution accomplished by chromatographic separation of the hexa-acetates of the condensation products of (+)-gossypol with (S)-1-methylphenethylamine followed by acid hydrolysis of the 2 main hexa-acetate, to give (+)- and (-)-gossypol with identical mp and alpha D values, was reported. Treatment of racemic gossypol with either (R)- or (S)-methylphenethylamine afforded yellow solids with mp 197-200 degrees C and m/z 753 (M + 1)+. By quick chromatography of the condensation products of either the (S) or (R) amine with (+)-gossypol on a silica column with diethyl ether-light petroleum as eluant, pure compounds were obtained. The compounds were assigned as (S)-amino-(+)-gossypol and (R)-amino-(-)-gossypol. These gossypols contained less than 5% of their antipodes. Although different in their antifertility action, the (+ or -), (+), and (-) isomers of gossypol demonstrate the same degree of inhibitory activity against the enzyme lactate dehydrogenase-X. Comparison of the antifertility action of the 3 isomers in male rats revealed that (-)-gossypol in half the dose of the (+ or -) isomer showed comparable activity, while the (+)-gossypol proved to be inactive.