Preparation of phosphopeptide thioesters by Fmoc- and Fmoc(2-F)-solid phase synthesis

Efficient methods for the preparation of phosphopeptide thioesters were examined, using Fmoc-based solid-phase method. Phosphopeptide thioesters were obtained in good yields by the use of 1-methylpyrrolidine, hexamethyleneimine and 1-hydroxybenzotriazole in a DMSO-DMF (1:1, v/v) solution for deblocking the Fmoc groups. Epimerization, which is often observed at the C-terminal amino acid, was effectively suppressed by shortening the time of deblocking process via the use of highly base sensitive Fmoc(2-F) groups for alpha-amino protection.