Diastereoselective Total Synthesis and Structural Confirmation of Surugamide F.

Surugamide F is a linear decapeptide (1) isolated along with the cyclic octapeptides surugamides A-E (2-6), from a marine-derived Streptomyces species. The linear peptide 1 is produced by two nonribosomal peptide synthetases (NRPSs) encoded in adjacent open reading frames, which are further flanked by an additional pair of NRPS genes responsible for the biosyntheses of the cyclic peptides 2-6. While the cyclic peptides 2-6 were identified to be cathepsin B inhibitors, the biological activity of the new metabolite 1 still remained unclear. In order to elucidate its unique biosynthetic pathway and biological activity in detail, we planned to develop an efficient synthetic route toward 1. Here we report the diastereoselective total synthesis of 1, utilizing 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis. During this study, we found that the structural correction of 1 was required, due to the mislabeling of the commercially obtained 3-amino-2-methylpropionic acid, and the true structure of 1 was corroborated by the chemical synthesis and chromatographic comparison.