A convenient synthesis of difficult medium-sized cyclic peptides by Staudinger mediated ring-closure?

Organic & Biomolecular Chemistry Pub Date: 2012-08-23 DOI: 10.1039/C2OB25996F

Abstract

Novel, efficient and mild preparation of 7- and 8-membered cyclic di- and 10-membered cyclic tripeptides containing α-, β- or γ-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.

Graphical abstract: A convenient synthesis of difficult medium-sized cyclic peptides by Staudinger mediated ring-closure
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