The facile synthesis of ala-glu-tyr( P)-ser-ala by ‘Global’ di-t-butyl N,N-diethylphosphoramidite ‘Phosphite-triester’ phosphorylation of a resin-bound peptide

Abstract

The O-phosphotyrosyl-containing peptide, Ala-Glu-Tyr( P)-Ser-Ala, was prepared by a methodology which featured ‘phosphite-triester’ phosphorylation of a resin-bound Tyr-containing peptide. The peptide-resin was assembled by Fmoc/solid phase peptide synthesis using HBTU as the coupling reagent and the tyrosyl residue incorporated as Fmoc-Tyr-OH. The peptide-resin was phosphorylated using di-t-butyl N,N-diethylphosphonamidite/ 1 H-tetrazole followed by m-chloroperoxybenzoic acid oxidation. Simultaneous peptide-resin cleavage and peptide deprotection was effected by 5% anisole/TFA to give the crude Tyr( P)-peptide in high yield and in >95% purity.