Synthesis of the Isotopically Labelled C ‐Terminal Fragment of Zervamicin: An Approach to the Synthesis of Aib‐Containing Peptides

The isotopically labelled C ‐terminal fragment of zervamicin, H‐Hyp 10 ‐[4,4‐ 2 H 2 ‐Gln]‐Aib‐Hyp‐Aib‐Pro‐Phl 16 , has been synthesized in solution by a Fmoc/ tert ‐butyl strategy in 28% overall yield. The Fmoc group was removed by reaction for 2 min with 0.1 M NaOH in dioxane/methanol/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 with 50% TFA in CH 2 Cl 2 for 30 min without significant cleavage of the acid‐labile Aib‐Pro and Aib‐Hyp peptide bonds.