Chemical synthesis of15N-labeled analogues of zervamicin IIB

Analogues of 16-membered peptide antibiotic zervamicin IIB with the Gln³ and Gln¹¹ residues¹⁵N-labeled at the Cα-atoms were synthesized by coupling the antibiotic segments (1–4), (5–9), and (10–16). In turn, these were prepared by a stepwise chain elongation in solution starting from theirC-termini using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as an activating agent. The sterically hindered 2-aminoisobutyric acid was introduced by the BOP-dimethylaminopyridine system with the preactivation of the carboxyl component. The segment condensation was performed with the use of the 6-trifluoromethylbenzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate activating reagent. The homogeneity of the resulting zervamicin analogues was confirmed by HPLC, and their structures were proved by NMR spectroscopy and FAB mass spectrometry.