Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators

Na Ye, Xiangtao Xu, Fuying Li, Mengmeng Ning, Zhiqing Liu, Yuqing Cao, Ying Leng, Ao Zhang

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

RuCl 3/NaIO 4-initiated oxidation of oxiranemethanols was investigated, and two products, oxirane-2-carboxylic acid and (5′-oxotetrahydrofuran-3-yl)acetic acid, were obtained in variant ratios. The product structures were determined and a tentative mechanism involving oxidation-rearrangement-oxidation process was proposed. Glucokinase enzymatic assay revealed that oxiranecarboxamides 4a-c retained moderate GK activation potency with amide 4a showing an EC 50 value of 584 nM and a high activation fold of 3.14. However, (5′-oxotetrahydrofuran-3-yl)acetamide 11a is inactive. This study not only provided an alternative protocol to access (5′-oxotetrahydrofuran-3-yl)acetic acid analogs, but also yielded nanomolar GA activators (esp. 4a) for further structure-activity relationship study.

Original languageEnglish (US)
Pages (from-to)4738-4742
Number of pages5
JournalTetrahedron Letters
Volume53
Issue number35
DOIs
StatePublished - Aug 29 2012

Keywords

  • Arylacetamides
  • Glucokinase activators
  • Oxo-rearrangement
  • Ruthenium-catalyzed

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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