A Robust, Recyclable Resin for Decagram Scale Resolution of ( ±

ISSN:1433-7851ISSN:1521-3773ISSN:0570-083

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

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

Synthetic Strategies for Macrocyclic Peptides

Peptide macrocycles form an outstanding class of natural and synthetic bioactive compounds. This chapter discusses synthetic strategies for the final ring‐closing reaction by the widely employed and versatile processes of lactamization, lactonization, and disulfide bridge formation. According to the nature of the chemical bond found in the backbone, cyclic peptides can be classified in two major categories: homodetic peptides and heterodetic peptides. In principle, all methods suitable for peptide bond formation can be applied for head‐to‐tail macrocyclization of linear peptides; however the reaction usually proceeds more slowly than the corresponding bimolecular version. During synthesis design, the C‐terminal amino acid of the linear precursor and the coupling reagent should be carefully chosen to minimize epimerization at the C‐terminal residue during cyclization. In many cases, the solution‐phase strategy is the best choice for performing the macrocyclization step, especially when larger quantities of cyclic peptide are required