Synthesis of Mixed α/β2,2-Peptides by Site-Selective Ring-Opening of Cyclic Quaternary Sulfamidates

A method for site- and stereoselective peptide modification using a cyclic sulfamidate scaffold containing peptides is described. A peptide synthesis strategy allowing the rapid generation of mixed α/β-peptides incorporating a sulfamidate residue, derived from 2-methylisoserine, has been generalized. The unique electrophilic nature of this scaffold for nucleophilic substitution at a quaternary center with total inversion of its configuration, which was demonstrated computationally, allows for site-selective conjugation with various nucleophiles, such as anomeric thiocarbohydrates and pyridines. This strategy provides rapid access to complex thioglyco-α/β-conjugates and charged α/β-peptides.