Novel Reactions in the Cephalostatin Series

Abstract

This work aimed at selective synthesis of analogues of cephalostatin 1, a highly anti-cancer marine natural product according to NCI measurements. We summarized here the work done in our laboratories of five years studying the selectivity of certain reactions of cephalostatin-like bis-steroidal pyrazines and hence, the biological activity variation. This study includes chemo-, regio-and stereoselective reactions of analogues starting from the symmetrical bis-steroidal diketone (3), which can be synthesized in a gram scale from the commercially available hecogenine acetate (1a). The following routes have been tested: the regioselective hydroboration of the exocyclic double bond at C-12, the regioselective F-ring opening of the spiroketals moieties, the chemo-and regioselective hydroboration of 14,15 double bond and finally, the chemo-and regioselective reduction of the carbonyl group at C-12.