Thiocoraline is a bicyclic octadepsipeptide that has been previously shown to have robust antitumor activity against various cancer cells. Thiochondrilline C is a structurally similar natural product, but with a significantly lower molecular weight. It was isolated from a marine Verrucosispora sp. (Strain WMMA107) and has been shown to have moderate cytotoxicity against the A549 human cancer cell line. However, the ligand efficiency of thiochondrilline C (C25H31N5O7S3; EC50 = 2.9 �M) and thiocoraline (C48H56N10O12S6; EC50 = 0.010 �M) for inhibiting the growth of this cell line are 0.14 and 0.11, respectively, indicating that derivatives of thiochondrilline C may represent attractive lead structures for medicinal chemistry optimization. Herein we report the synthesis of thiochondrilline C by N-terminal extension of the peptide, oxidative disulfide bond formation and heterocycle installation as key steps. Finally, the rationale for designing thiochondrilline C derivatives as possible mimetics of thiocoraline will also be presented.

Synthetic approaches to thiochondrilline C and potential use of its derivatives as mimetics of the antitumor bicyclic octadepsipeptide thiocoraline

247th National Meeting (2014)

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