N(Ï)-2-Naphthylmethoxymethyl-Protected Histidines: Scalable, Racemization-Free Building Blocks for Peptide Synthesis

Kohei Torikai, Ryota Yanagimoto, Louis A. Watanabe

Research output: Contribution to journalArticle

Abstract

Histidine (His) racemizes with relative ease during peptide synthesis. One strategy to suppress this racemization is to protect the nitrogen atom of the imidazole moiety in His with a suitable protecting group. Among the numerous protecting groups that have already been tested, the p-methoxybenzyloxymethyl (PMBOM) group on the Ï-nitrogen atom effectively suppresses the racemization. However, a large-scale synthesis of N(Ï)-PMBOM-protected derivatives has hitherto been hampered by the requirement of a freshly prepared unstable reagent. Herein we report the synthesis of N(Ï)-2-naphthylmethoxymethyl (NAPOM)-protected His derivatives, which can be prepared on a gram scale and do not suffer from the aforementioned instability problems. Furthermore, these NAPOM-protected His derivatives suppress the racemization in Boc- A nd Fmoc-based peptide synthesis.

Original languageEnglish
Pages (from-to)448-453
Number of pages6
JournalOrganic Process Research and Development
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 20 2020

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All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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