ORGN 514

The Caribbean gorgonian octocoral Eunicea succinea is a rich source of bioactive cembranolides such as eunicin. Chemical transformations to eunicin have been carried out to develop chemotherapeutic agents that could be used as pharmacological probes. For instance, new analogs are being synthesized in our laboratory through the careful oxidative cleavage of eunicin at the D⁷ position with the purpose of increasing their biological activity. The synthetic sequence also includes the photochemical transformation of an intermediate cembranolide-type pyrazoline into an a-cyclopropyl-g-lactone followed by ozonolysis thus yielding the open-chain bilactone shown below. The main structural feature among these analogs is that they possess lactone and cyclic ether functionality whose chemical architecture is somewhat reminiscent of that found in several cytotoxic polyethers of marine origin. Some of these analogs have displayed cytotoxic activity against leukemia and CNS cancer cell lines. Random screening of some of these analogs as possible antimalarial agents is currently in progress.