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

doi:10.1016/j.tetlet.2012.06.111

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 journal › Article › peer-review

7 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 language	English (US)
Pages (from-to)	4738-4742
Number of pages	5
Journal	Tetrahedron Letters
Volume	53
Issue number	35
DOIs	https://doi.org/10.1016/j.tetlet.2012.06.111
State	Published - Aug 29 2012
Externally published	Yes

Keywords

Arylacetamides
Glucokinase activators
Oxo-rearrangement
Ruthenium-catalyzed

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tetlet.2012.06.111

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@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",

note = "Funding Information: The authors are grateful to the Chinese National Science Foundation (30772625, 81072528), the Shanghai Commission of Science and Technology (10410702600, 10JC1417100, 10dz1910104), and National Science & Technology Major Project on {\textquoteleft}Key New Drug Creation and Manufacturing Program{\textquoteright} (2009ZX09301-001, 2009ZX09103-062). ",

year = "2012",

month = aug,

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

N1 - Funding Information: The authors are grateful to the Chinese National Science Foundation (30772625, 81072528), the Shanghai Commission of Science and Technology (10410702600, 10JC1417100, 10dz1910104), and National Science & Technology Major Project on ‘Key New Drug Creation and Manufacturing Program’ (2009ZX09301-001, 2009ZX09103-062).

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

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JO - Tetrahedron Letters

JF - Tetrahedron Letters

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ER -

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

Abstract

Keywords

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