Didemnins, tamandarins and related natural products

Since the discovery and isolation of the didemnin family of marine depsipeptides in 1981, the synthesis and biological activity of its congeners have been of great interest to the scientific community. The didemnins have demonstrated antitumor, antiviral, and immunosuppressive activity at low nano- and femtomolar levels. Of the congeners, didemnin B was the first marine natural product to reach phase II clinical trials in the United States, stimulating many analogue syntheses to date. About two decades later, tamandarins A and B were isolated, and were found to possess very similar structure and biological activity to that of the didemnin B. These compounds have shown impressive biological activity and some progress has been made in establishing structure-activity relationships. However, their molecular mechanism of action still remains unclear. This review highlights the long-standing study of didemnins and its critical application towards the understanding of the molecular mechanism of action of tamandarins and their potential use as therapeutic agents.