Novel methodology for the solid-phase synthesis of phosphinic peptides

A novel. versatile strategy for the solid phase synthesis of phosphinic pep tides is developed in which the phosphorus- carbon bond is formed on a poly mer support during peptide synthesis. The formation of bis(trimethylsilyl) 1-(allyloxy-carbonylamino)ethylphosphonite from 1-(allyloxycarbonylamino)et hylphosphinic acid is investigated, as well as the Michael addition of the former to a resin-bound acrylate. Conditions are also established for the c lean, quantitative conversion of a resin-bound, N-terminus acryloylated pep tide with bis(trimethylsilyl) 1-(allyloxycarbonylamino)ethylphosphonite. Co nventional peptide synthesis is then employed to obtain a phosphinic undeca peptide in high yield and purity.