Total Synthesis and Stereochemical Assignment of Sunshinamide and Its Anticancer Activity.

Total synthesis of cyclodepsipeptide sunshinamide has been achieved for the first time using a convergent approach. The key features of this synthesis comprise Crimmins acetate aldol, Shiina esterification, amide coupling, macrolactamization, and an I-2-mediated deprotection with concomitant disulfide-bridge formation. This synthetic study enabled the unambiguous determination of the stereochemistry of the unassigned stereocenter of the isolated sunshinamide. The cytotoxicity of sunshinamide and one of its analogues was evaluated against different cancerous and noncancerous human cell lines, which revealed their attractive and selective activities toward cancer cells at very low concentrations.