Abstract
Novel, efficient and mild preparation of 7- and 8-membered cyclic di- and 10-membered cyclic tripeptides containing alpha-, beta- or gamma-amino acid residues is effected by a Staudinger-mediated ring closure. Medium-sized cyclic di- and tripeptides - recognized as difficult targets - were obtained in moderate to good yields according to a straightforward sequence. Empirical force-field calculations were undertaken to determine their conformational behaviors and showed high levels of similarity with X-ray results. A computational study at the B3LYP/6-31+G** level of theory afforded information regarding the impact of the sequence, ring-size and substitution on the activation barriers for the cyclization of azido peptide thioesters.