Total Synthesis of Violaceoid A and (-)- and (+)-Violaceoid B

The first total synthesis of violaceoid A, a cytotoxic agent, and the asymmetric total synthesis of (-)- and (+)-violaceoid B are reported. The precursor was accessed by desymmetrization of a substituted quinol moiety, and the racemic secondary alcohol was kinetically resolved using a chiral nucleophilic catalyst. The asymmetric synthesis of (-)- and (+)-violaceoid B elucidated the absolute configuration of the naturally occurring violaceoid B. Synthetic violaceoid A inhibited the growth of human breast cancer cell lines MCF-7 and Hs 578T at concentrations of less than 100 mu M, while (S)- and (R)-violaceoid B were inactive.