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Late-Stage Functionalization of Peptides and Cyclopeptides Using Organozinc Reagents
Marcel Leroux1, Thomas Vorherr2, Ian Lewis2
1Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
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.
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