Synthesis and evaluation of Apogossypol atropisomers as potential Bcl-xL antagonists

Anti-apoptotic Bcl-2 family proteins such as Bcl-2 and Bcl-XL have been recently validated as targets for the discovery of novel anti-cancer agents. We previously reported that racemic (+/−) Apogossypol, a semi-synthetic compound derived from the natural product Gossypol, binds and inhibits Bcl-2 and Bcl-XLin vitro and in cell. Given that (+) and (−) Gossypol display different proapoptotic activities, here we report on the synthesis of (+) and (−) Apogossypol and the evaluation of their in vitro and cellular activity.