Total synthesis of 14,21-diepi-squamocin-K

A new method to prepare annonaceous acetogenins is described in the synthesis of the 14,21-diepimer (14) of squamocin-K. The synthesis utilized the controlled sequence of ring-closing metathesis (RCM) and cross metathesis (CM) reactions to incorporate the stereocenters and skeleton from (3R,4R)-1,5-hexadiene-3,4-diol and 10-chloro-1-decene. The lactone moiety was attached through nucleophilic substitution and achieved the desymmetrization. Inhibitory activities of 14 against human hormone-refractory prostate cancer cell line (PC-3) were also evaluated.