Mechanistic Insight into the TBHP-Mediated Decarboxylative Condensation of a-Ketoacids: Reaction Development and Application to Oligopeptide Synthesis

With the aim of achieving the convergent elongation of peptide chains, an amide bond formation reac-tion that enables a peptide fragment coupling has long been pursued. The decarboxylative amidation recently reported by our group is a potential solution to this problem. In this article, a mechanisti...

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Bibliographic Details
Published inChemical & pharmaceutical bulletin Vol. 71; no. 5; pp. 354 - 359
Main Authors Yoshikawa, Kosuke, Kato, Natsuki, Nanjo, Takeshi, Takemoto, Yoshiji
Format Journal Article
LanguageEnglish
Published TOKYO Pharmaceutical Soc Japan 01.05.2023
Subjects
Chemistry
Chemistry, Medicinal
Chemistry, Multidisciplinary
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Physical Sciences
Science & Technology
amidation
peptide
decarboxylation
AMIDE
COUPLING REAGENTS
alpha-ketoacid
fragment condensation
ALPHA-KETO ACIDS
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Summary:With the aim of achieving the convergent elongation of peptide chains, an amide bond formation reac-tion that enables a peptide fragment coupling has long been pursued. The decarboxylative amidation recently reported by our group is a potential solution to this problem. In this article, a mechanistic analysis of the t-butyl hydroperoxide (TBHP) mediated-decarboxylative amidation of a-ketoacids that results in a significant advance in convergent peptide synthesis is described. Despite the observation of epimerization with low bulk substrates in preliminary studies, a systematic examination and understanding of the reaction mechanism enabled the development of a modified epimerization-free reaction whereby peptide fragment couplings using peptide a-ketoacids were successfully achieved.
ISSN:0009-2363