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

3 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Glucokinase
Ethylene Oxide
Acetic Acid
Oxidation
Enzyme Assays
Structure-Activity Relationship
Carboxylic Acids
Chemical activation
Amides
Assays
acetamide

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators. / Ye, Na; Xu, Xiangtao; Li, Fuying; Ning, Mengmeng; Liu, Zhiqing; Cao, Yuqing; Leng, Ying; Zhang, Ao.

In: Tetrahedron Letters, Vol. 53, No. 35, 29.08.2012, p. 4738-4742.

Research output: Contribution to journalArticle

Ye, Na ; Xu, Xiangtao ; Li, Fuying ; Ning, Mengmeng ; Liu, Zhiqing ; Cao, Yuqing ; Leng, Ying ; Zhang, Ao. / Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators. In: Tetrahedron Letters. 2012 ; Vol. 53, No. 35. pp. 4738-4742.
@article{9b470331bfbb442aac7e484a77ae07c5,
title = "Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators",
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.",
keywords = "Arylacetamides, Glucokinase activators, Oxo-rearrangement, Ruthenium-catalyzed",
author = "Na Ye and Xiangtao Xu and Fuying Li and Mengmeng Ning and Zhiqing Liu and Yuqing Cao and Ying Leng and Ao Zhang",
year = "2012",
month = "8",
day = "29",
doi = "10.1016/j.tetlet.2012.06.111",
language = "English (US)",
volume = "53",
pages = "4738--4742",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Limited",
number = "35",

}

TY - JOUR

T1 - Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators

AU - Ye, Na

AU - Xu, Xiangtao

AU - Li, Fuying

AU - Ning, Mengmeng

AU - Liu, Zhiqing

AU - Cao, Yuqing

AU - Leng, Ying

AU - Zhang, Ao

PY - 2012/8/29

Y1 - 2012/8/29

N2 - 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.

AB - 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.

KW - Arylacetamides

KW - Glucokinase activators

KW - Oxo-rearrangement

KW - Ruthenium-catalyzed

UR - http://www.scopus.com/inward/record.url?scp=84864401430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864401430&partnerID=8YFLogxK

U2 - 10.1016/j.tetlet.2012.06.111

DO - 10.1016/j.tetlet.2012.06.111

M3 - Article

AN - SCOPUS:84864401430

VL - 53

SP - 4738

EP - 4742

JO - Tetrahedron Letters

JF - Tetrahedron Letters

SN - 0040-4039

IS - 35

ER -