Synthesis of the15N-Gln11 labeled peptaibol antibiotic zervamicin-IIB

Abstract

Synthesis of zervamicin IIB, specifically labeled at the u-position of glutamine-ll with 15N, was achieved by the Fmoc/tert.-butyl strategy in solution using a fragment condensation approach. Three fragments of zervamicin IIB were obtained by stepwise elongation with Fmoc amino acids using BOP as a coupling reagent. For the introduction of the highly sterically hindered c~-aminoisobutyric acid residues, BOP/DMAP activation was applied. Peptide fragments were coupled by means of the coupling reagent, CF3-PyBOP. Using the strategy developed, zervamicin lib specifically 15N labeled has been synthesized in 30% overall yield based on the isotopically labeled amino acid. From 600 MHz NMR spectroscopy the position of the 15N-label was clearly detected. The isotope enrichment (98 + 2%) was determined by FAB-mass spectrometry.

15N and 31P Solid-State NMR Investigations on the Orientation of Zervamicin II and Alamethicin in Phosphatidylcholine Membranes

“…Zervamicin IIB, specifically labeled at the R-position of glutamine-11 with 15 N, was achieved by the Fmoc-tert-butyl strategy in solution using a fragment condensation approach as has been described elsewhere (47). From 600 MHz solution-state NMR spectroscopy the position of the 15 N label was clearly detected, and the isotope enrichment (98% ( 2%) was determined by FAB mass spectrometry.…”