Late‐Stage Functionalization of Peptides and Cyclopeptides Using Organozinc Reagents. Issue 24 (9th May 2019)

• Record Type: Journal Article
• Authors: Leroux, Marcel; Vorherr, Thomas; Lewis, Ian; Schaefer, Michael; Koch, Guido; Karaghiosoff, Konstantin; Knochel, Paul
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 24(2019)
• Page Start: 8231
• Page End: 8234
• Publication Date: 2019-05-09
• Subjects: cross-coupling -- cyclopeptides -- membrane permeability -- organozinc -- peptides; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201902454
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: We report a new late‐stage functionalization of small peptides and cyclopeptides relying on the Negishi cross‐coupling of readily prepared iodotyrosine‐ or iodophenylalanine‐containing peptides with aryl‐, heteroaryl‐, and alkylzinc pivalates or halides. In silico and in vitro determinations of membrane permeability parameters of the modified cyclopeptides showed that in most cases, the solubility was improved by the introduction of polar pyridyl units while the cell‐membrane permeability was maintained. Abstract : Just in time : A late‐stage functionalization of small peptides and cyclopeptides relies on the Negishi cross‐coupling of readily prepared iodotyrosine‐ or iodophenylalanine‐containing peptides with aryl‐, heteroaryl‐ and alkylzinc pivalates or halides. In most cases, the solubility was improved by the introduction of polar pyridyl units, while the cell‐membrane permeability was maintained.