Evidence for a trianion intermediate in the metalation of 4-hydroxy-6,7-dimethoxy-8-methyl-2-naphthoic acid. Methodology and application to racemic 5,5'-didesisopropyl-5,5'-dialkylapogossypol derivatives.

The metalation of 4-hydroxy-6,7-dimethoxy-8-methyl-2-naphthoic acid (8) affording trianion 6 is presented and applied to the regioselective efficient construction of a series of 5,5'-didesisopropyl-5,5'-dialkylapogossypol derivatives 3 that are potent pan-active inhibitors of antiapoptotic Bcl-2 family proteins.