Synthesis, structures, and acute toxicity of gossypol nonsymmetrical aldehyde derivatives

Nonsymmetrical aldehyde derivatives of gossypol, a yellow polyphenolic pigment of cottonseed, were synthesized by reactions with ammonia, aniline, 4-aminoantipyrine, and barbituric acid. Their structures were determined by UV spectrophotometry and IR and 1H NMR spectroscopy methods. Their acute toxicities in white mice were compared with those of gossypol and the corresponding symmetrical analogues. It was demonstrated that in general, the fewer free aldehyde groups available in the gossypol derivative, the lower its acute toxicity. Only in the case of a nonsymmetrical gossypol derivative bearing a 4-aminoantipyrine residue did we observe a deviation from the above correlation: its symmetrical counterpart was even more toxic, but still less toxic than gossypol.