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

[Image: see text] 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 9 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).