SYNTHESIS OF THE ISOTOPICALLY LABELED C-TERMINAL FRAGMENT OF ZERVAMICIN - AN APPROACH TO THE SYNTHESIS OF AIB-CONTAINING PEPTIDES

The isotopically labelled C-terminal fragment of zervamicin, -Hyp(10)- [4,4-H-2(2)-Gln]-Aib-Hyp-Aib-Pro-Phl(16), has been synthesized in solu tion by a Fmoc/tert-butyl strategy in 28% overall yield. The Fmoc grou p was removed by reaction for 2 min with 0.1 M NaOH in dioxane/methano l/water, (30:9:1, v:v:v). The couplings of the sterically hindered Aib residues were achieved by means of either BOP/DMAP activation or Fmoc -Aib-Cl. Acid deprotection of the peptide was performed by reaction wi th 50% TFA in CH2Cl2 for 30 min without significant cleavage of the ac id-labile Aib-Pro and Aib-Hyp peptide bonds.