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Total synthesis of zervamicin IIB and its deuterium‐labelled analogues
Author(s) -
Ogrel Alexei,
Bloemhoff Wim,
Lugtenburg Johan,
Raap Jan
Publication year - 1997
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/(sici)1099-1387(199705)3:3<193::aid-psc101>3.0.co;2-6
Subject(s) - chemistry , total synthesis , peptide synthesis , reagent , yield (engineering) , steric effects , nuclear magnetic resonance spectroscopy , amino acid , peptide , residue (chemistry) , stereochemistry , organic chemistry , biochemistry , materials science , metallurgy
For the first time the total synthesis of the peptaibol antibiotic zervamicin IIB is described. Synthesis of this peptaibol 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 α‐aminoisobutyric acid residues BOP/DMAP activation was applied. The Fmoc group was removed by reaction with 0.1 M NaOH in dioxane/methanol/water (30/9/1, v/v/v). Peptide fragments were coupled by means of a new coupling reagent, CF 3 ‐PyBOP. Using the strategy developed, zervamicin IIB and two analogues specifically deuterium‐labelled at different positions of the glutamine‐11 residue have been synthesized in 40% overall yield based on the isotopically labelled amino acid and with 98±2% of isotope enrichment. FAB mass spectroscopy, 600 MHz 1 H‐NMR spectroscopy and high‐performance liquid chromatography provided convincing evidence that the synthetic products, zervamicin IIB and its deuterium‐labelled analogues, fully correspond to the naturally occurring zervamicin IIB. © 1997 European Peptide Society and John Wiley & Sons, Ltd.