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Sulfanylmethyldimethylaminopyridine as a Useful Thiol Additive for Ligation Chemistry in Peptide/Protein Synthesis

Kento Ohkawachi, Daishiro Kobayashi, Kyohei Morimoto, Akira Shigenaga, Masaya Denda, Kenzo Yamatsugu, Motomu Kanai, Akira Otaka

2020Organic Letters17 citationsDOIOpen Access PDF

Abstract

Sulfanylmethyl-installed dimethylaminopyridine, 2-sulfanylmethyl-4-dimethylaminopyridine (2), has an acidic thiol group comparable to that in aryl thiols due to the formation of a zwitterion consisting of a thiolate anion and a pyridinium cation. It can be used as an additive for native chemical ligation. The alkyl thiol in 2 allows it to be used for the one-pot native chemical ligation–desulfurization protocol in peptide synthesis. The utility of 2 in the synthesis of cyclic peptides is demonstrated.

Topics & Concepts

Native chemical ligationChemistryZwitterionThiolPyridiniumChemical ligationAlkylPeptideLigationCysteineCombinatorial chemistryHydrazidePeptide synthesisOrganic chemistryMoleculeBiochemistryMolecular biologyEnzymeBiologyChemical Synthesis and AnalysisSulfur-Based Synthesis TechniquesClick Chemistry and Applications
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