Chemical synthesis of 15N-labeled zervamicins IIB
Rimawi, W.H.; Ogrel, A.A.; Raap, J.; Shvets, V.I.
Bioorganicheskaia Khimiia 26(11): 808-816
2000
ISSN/ISBN: 0132-3423 PMID: 11696891 Document Number: 514077
Analogues of 16-membered peptide antibiotic zervamicin IIB with the Gln3 and Gln11 residues 15N-labeled at the C alpha-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 their C-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.