Triazole-Linked Iminosugars and Aromatic Systems as Simplified UDP-Galf Mimics: Synthesis and Preliminary Evaluation as Galf-Transferase Inhibitors

被引：10

作者：

Cocaud, Chloe ^{[1
]}

Maujoin, Audrey ^{[1
]}

Zheng, Ruixiang B. ^{[2
,3
]}

Lowary, Todd L. ^{[2
,3
]}

Rodrigues, Nuno

Percina, Nathalie ^{[1
]}

Chartier, Agnes ^{[1
]}

Buron, Frederic ^{[1
]}

Routier, Sylvain ^{[1
]}

Nicolas, Cyril ^{[1
]}

Martin, Olivier R. ^{[1
]}

机构：

[1] Univ Orleans, UMR CNRS 7311, Inst Chim Organ & Analyt, Rue Chartres,BP 6759, F-45067 Orleans 2, France

[2] Univ Alberta, Gunning Lemieux Chem Ctr, Alberta Glyc Ctr, 11227 Saskatchewan Dr, Edmonton, AB T6G 2G2, Canada

[3] Univ Alberta, Gunning Lemieux Chem Ctr, Dept Chem, 11227 Saskatchewan Dr, Edmonton, AB T6G 2G2, Canada

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2017年 / 2017卷 / 41期

关键词：

Carbohydrates; Iminosugars; Click chemistry; Inhibitors; Transferases; Biological activity; DIVERSITY-GENERATING ELEMENT; 5'-METHYLTHIOADENOSINE/S-ADENOSYLHOMOCYSTEINE NUCLEOSIDASE; BIOLOGICAL-PROPERTIES; ESCHERICHIA-COLI; ANALOGS; GALACTOFURANOSYLTRANSFERASE; PROPARGYLATION; MYCOBACTERIA; REAGENTS; GAUCHER;

D O I：

10.1002/ejoc.201701283

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The convenient preparation of 1,4-dideoxy-1,4-imino-l-arabinitol derivatives bearing a propargyl group through the addition of a trimethylsilylpropargyl Grignard reagent to an N-sulfinylglycosylamine is reported. One of these compounds was coupled by a triazole tether to various aromatic and heteroaromatic groups to give structures that can be considered to be simplified mimics of UDP-Galf, the substrate of GlfT2, a galactofuranosyltransferase present in mycobacteria. The new compounds were evaluated as inhibitors of this enzyme and were found to have significant activity (IC50 values in the high mu m to low mm range), despite the absence of the diphospho linkage present in the parent sugar nucleotide.

引用

页码：6192 / 6201

页数：10

共 42 条

[1] Mercury-free preparation and selective reactions of propargyl (and propargylic) grignard Reagents [J].