The synthesis of a N^γ‐phthalyl‐N^α‐methyl‐α, γ‐diaminobutyryl congener of virginiamycin S₁

Abstract

Abstract A synthesis of Z‐Thr 1 ‐D‐Abu 2 ‐Pro 3 ‐MePhe 4 ‐MeA 2 bu(γPht) 5 ‐Phg 6 ‐ (A 2 bu = α, γ‐diaminobutyric acid) is reported using the very efficient coupling agent BOP‐Cl (N, N'‐bis(3‐oxo‐2‐oxazolidinyl)phosphinic chloride) for imino acid peptide bond formation. The total yield is 11% for the 5 coupling steps and one lactonization. The final step was a cyclization between residues 5 and 6, after (i) first t‐Boc acidic deprotection with 85% HCOOH of the linear precursor Z‐Thr (N α ‐Boc‐Phg‐O‐)‐D‐Abu‐Pro‐MePhe‐MeA 2 bu(γPht)‐OBu followed by (ii) acidic saponification (Tfa) of the t‐Bu ester. This sequence was found to be a prerequisite, in view of the extreme lability of the 4–5 peptide bond under acidic conditions.