Ring-closing metathesis for the synthesis of side chain knotted pentapeptides inspired by vancomycin

ten Brink, H.T., Rijkers, D.T.S., Kemmink, J., Hilbers, H.W. and Liskamp, R.M.J. (2004) Ring-closing metathesis for the synthesis of side chain knotted pentapeptides inspired by vancomycin. Organic and Biomolecular Chemistry, 2(18), pp. 2658-2663. (doi: 10.1039/b408820d)

Abstract

A versatile method for the synthesis of bicyclic side chain knotted peptides inspired by vancomycin is described. The synthetic approach is based on the incorporation of a central amino acid derivative 3 having two allylic groups—introduced by a Stille coupling—into pentapeptide 8 containing two allylated serine residues. Treatment of this bis-ring-closing metathesis precursor with 2nd generation Grubbs catalyst results in the formation of a bicyclic pentapeptide with the correct side chain to side chain connectivity pattern as observed in vancomycin: i − 2 → i, i → i + 2. Modelling studies using MacroModel hint at a cavity-like structure of the bicyclic pentapeptide which may bind suitable ligands.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert
• Authors: ten Brink, H.T., Rijkers, D.T.S., Kemmink, J., Hilbers, H.W., and Liskamp, R.M.J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Organic and Biomolecular Chemistry
• ISSN: 1477-0520
• ISSN (Online): 1477-0539