Gossypol

Gossypol is a natural phenol derived from the cotton plant (genus Gossypium). Gossypol is a phenolic aldehyde that permeates cells and acts as an inhibitor for several dehydrogenase enzymes. It is a yellow pigment.

Among other things, it has been tested as a male oral contraceptive in China. In addition to its putative contraceptive properties, gossypol has also long been known to possess antimalarial properties. Other researchers are investigating the anticancer properties of gossypol.

Biosynthesis

Gossypol is a terpenoid aldehyde which is formed metabolically through acetate via the isoprenoid pathway. Sesquiterpene dimer undergoes a radical coupling reaction to form gossypol. The biosynthesis begins when geranyl pyrophosphate (GPP) and isopentenyl pyrophosphate (IPP) are combined to make the sesquiterpene precursor farnesyl diphosphate (FPP). Cadinyl cation (1) is oxidized to 2 by (+)-d-cadinene synthase. The (+)-d-cadinene (2) is involved in making the basic aromatic sesquiterpene unit, homigossypol, by oxidation, which generates the 3 (8-hydroxy-d-cadinene) with the help of (+)-d-cadinene 8-hyroxylase. Compound 3 goes through various oxidative processes to make 4 (deoxyhemigossypol), which is oxidized by one electron into hemigossypol (5, 6, 7) and then undergoes a phenolic oxidative coupling, ortho to the phenol groups, to form gossypol (8). The coupling is catalyzed by a hydrogen peroxide-dependent peroxidise enzyme, which results in the final product.