Synthesis of the Simple Peptide Model Ac-Abu(PO₃H₂)-NHMe

Abstract

The simple model substrate AC-L-Abu(PO₃H₂)- NHMe was prepared by the use of the protected 4( diethylphosphono ) butanoic acid derivative Boc -Abu(PO₃Et₂)-OH in the Boc mode of solution phase peptide synthesis. The protected peptide model Ac-Abu(P0₃Et₂)- NHMe was prepared by initial reaction of the isobutoxycarbonyl mixed anhydride of Boc-Abu(PO₃Et₂)-OH with N-methylamine followed by cleavage of the Boc group from Boc -Abu(PO₃Et₂)- NHMe with 4 M HCl/dioxan and N- acetylation of H-Abu(PO₃Et₂)-NHMe.HCl with the isobutoxycarbonyl mixed anhydride of acetic acid. Cleavage of the phosphonate ethyl groups was effected with 33% hydrogen bromidelacetic acid or 10% bromotrimethylsilane/acetonitrile to give AC-L-Abu(PO₃H₂)-NHMe in near-quantitative yield.