Salicylihalamide A is a novel, highly potent (GI50 = 7 +/- 2 nM for melanoma cell lines), cytotoxic macrolide isolated from the marine sponge Haliclona sp. The testing on this compound suggests the possibility of a novel mechanism of action different from the known cytotoxic compounds. It is crucial for the study of the mechanism of action of this class of compounds to develop convergent syntheses of salicylihalamide A and its structurally related natural or non-natural analogues. Preparation of these compounds may aid the development of novel cancer chemotherapeutic agents. With the biological implications in mind, convergent synthetic plans for salicylihalamide are proposed. These include exploratory employment of a novel methodology, alkenylboronate tethered ring closing metathesis. This methodology will be a valuable extension on the existing olefin metathesis reaction by providing a way to control stereochemistry of the product olefin. The synthesis proposed by using this methodology is versatile enough to provide not only salicylihalamide A itself, but also its structurally related compounds.
