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)

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Publisher's URL: http://dx.doi.org/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

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