RESUMEN
Gossypol has been resolved into its pure optical isomers by conversion into the Schiff's base derivative of (+)-phenylalanine methyl ester, normal or reverse phase chromatography and hydrolysis. Forty grams of pure (-)-gossypol has been prepared in a micronised form for assessment of its antifertility and toxicological effects.
PIP: There is a requirement for multigram quantities of the gossypol enantiomers to confirm claims of the antispermatogenic and antitumor properties of gossypol's (-) isomer. The authors have resolved gossypol into its pure optical isomers by conversion into the Schiff's base derivative of (+)-phenylalanine methyl ester and used normal or reverse phase chromatography and hydrolysis to assess its antifertility and toxicologic effects. 40 grams of pure (-)-gossypol were obtained and tested in adult male Golden Syrian hamsters. The 40 grams of resolved (-)-gossypol was dissolved in ethanol and the solution poured slowly into cold water. When administered at a dosage of 8 mg/kg/day, (-)-gossypol produced the same antifertility effects as twice that dose of racemic gossypol-acetic acid. The (+) isomer was without antifertility effect at the same dose. The observation of an enantioselective effect of the gossypol isomers on male fertility is significant in that it offers the possibility of reducing the drug dosage by half, perhaps minimizing side effects. In addition, the availability of 2 compounds that are chemically identical but differ in their biologic properties provides a valuable pair of probes. They can be used to examine gossypol's mechanism of action and distinguish between effects that are general properties of gossypol's reactive phenolic and aldehydic groups and effects that are specific properties related to the antifertility and antitumor activity of the (-) isomer.