Practical Strategy to 1,1'-Dideoxygossypol Derivatives from Gossypol and Its Antitumor Activities.

A practical and scalable route for the synthesis of 1,1'-dideoxygossypol from natural polyphenol product gossypol is described. The key step is the successful regioselective deacetylation of hexaacetyl apogossypol and the following reductive removal of hydroxyl groups. The two steps of deacetylation occurred on the different sites under different conditions. The synthetic route follows a simple protection-deprotection strategy, and the yields of each step are over 85%. The total yield of this 9-step synthesis is over 40%, which is much better than the reported total synthesis method. The antitumor results illustrate that 1,1'-hydroxyl groups are not necessary for antitumor activities. In addition, 1,1'-dideoxygossypol has superior aqueous solubility (215 mg/L) compared to gossypol (64 mg/L).