Synthesis of alkyne-bridged cyclic tripeptides toward constrained mimics of vancomycin

ten Brink, H.T., Rijkers, D.T.S. and Liskamp, R.M.J. (2006) Synthesis of alkyne-bridged cyclic tripeptides toward constrained mimics of vancomycin. Journal of Organic Chemistry, 71(5), pp. 1817-1824. (doi: 10.1021/jo051933m)

Abstract

The synthesis of a range of highly constrained cyclic tripeptides has been performed using either an intramolecular Sonogashira coupling or a macrolactamization as the final ring-closing reaction. Our approach gives access to rigidified 15-membered peptidic macrocycles based on the central ring system of vancomycin. Tripeptides 3a−c and dipeptide 11 were cyclized via an intramolecular Sonogashira reaction, and the cyclic peptides 4a−c and 15a were obtained in 6−23% yield. In contrast, macrolactamization of 12 and 17 resulted in the desired peptidic macrocycles 15b and 18 with 54−61% yield. Modeling studies hint at a distorted triple bond, which explains the low yield of the Sonogashira-based cyclization. Moreover, modeling data also showed that this class of peptidic macrocycles formed a cavity-like structure in which guest molecules may bind.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert
• Authors: ten Brink, H.T., Rijkers, D.T.S., and Liskamp, R.M.J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Journal of Organic Chemistry
• ISSN: 0022-3263