Late‐Stage Functionalization of Peptides and Cyclopeptides Using Organozinc Reagents

Abstract

We have reported a new late‐stage functionalization of small peptides and cyclopeptides using readily prepared iodotyrosine or iodophenylalanine containing peptides and performing Negishi cross‐couplings with aryl‐, heteroaryl‐ and alkyl‐zinc pivalates or halides. In‐silico and in‐vitro determinations of membrane permeability data of the modified cyclopeptides showed that in most cases, the solubility was improved while the cell‐membrane permeability was maintained by the introduction of polar pyridyl units.