Solid-phase synthesis of N-nosyl- and N-Fmoc-N-methyl-alpha-amino acids

We report here a convenient and simple solid-phase synthesis of N-nosyl-N-methyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids, important building blocks for the synthesis of conformationally restricted and protease-resistant natural peptides and peptide analogues. The methodology involves the use of 2-chlorotrityl chloride resin to temporarily protect the carboxylic group of alpha-amino acids and of diazomethane as the reagent to methylate the sulfonamidic function. The approach developed is particularly efficient also with alpha-amino acids bearing appropriately protected functionalized side chains.