Novel methodology for the solid-phase synthesis of phosphinic peptides

Abstract

A novel, versatile strategy for the solid phase synthesis of phosphinic peptides is developed in which the phosphorus–carbon bond is formed on a polymer support during peptide synthesis. The formation of bis(trimethylsilyl) 1-(allyloxycarbonylamino)ethylphosphonite from 1-(allyloxycarbonylamino)ethylphosphinic acid is investigated, as well as the Michael addition of the former to a resin-bound acrylate. Conditions are also established for the clean, quantitative conversion of a resin-bound, N-terminus acryloylated peptide with bis(trimethylsilyl) 1-(allyloxycarbonylamino)ethylphosphonite. Conventional peptide synthesis is then employed to obtain a phosphinic undecapeptide in high yield and purity.