Diastereoselective Total Synthesis and Structural Confirmation of Surugamide F

Abstract

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.

The Diversity, Metabolomics Profiling, and the Pharmacological Potential of Actinomycetes Isolated from the Estremadura Spur Pockmarks (Portugal)

“…Surugamide derivatives were found in seven Streptomyces strains: PTE-035, PTE-036, PTE-040, PTE-045, PTE-050, PTE-054, and PTE-064. To date, there are only five surugamides described in the literature [51,71]. The surugamide family contains several unknown derivatives (Figure 7A), thus suggesting that these actinomycetes are a promising source of new compounds to be further investigated.…”

A New Cyclase Family Catalyzing Head-to-Tail Macrolactamization of Non-ribosomal Peptides

“…We therefore recon rmed the absolute con guration of surugamide F by diastereoselective total synthesis (Scheme 1). 22 To prepare the optically pure AMPA residue, Evans asymmetric alkylation 23 of propionyl oxazolidinone with BOMCl was carried out. The removal of the benzyl group of 8a afforded a primary alcohol 9a, which was further converted to an amine 10a.…”

Identification and Total Synthesis of an Unstable Anticancer Macrolide Presaccharothriolide Z Produced by Saccharothrix sp. A1506

“…The synthesis of 17 commenced with the TBDPS protection of alcohol 18 , which had previously been synthesized on the multigram scale (Scheme ). The reductive cleavage of Evans’ chiral auxiliary produced alcohol 19 , which was then oxidized to aldehyde 20 by TEMPO and PhI­(OAc) 2 (83% yield over three steps). Subsequent Brown’s asymmetric allylation of 20 gave alcohol 21 .…”