A protecting group-free synthesis of deazathiamine: A step toward inhibitor design

被引：10

作者：

Zhao, Hong ^{[1
]}

de Carvalho, Luiz Pedro S. ^{[2
]}

Nathan, Carl ^{[2
]}

Ouerfelli, Ouathek ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, Organ Synth Core Facil, New York, NY 10021 USA

[2] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 22期

关键词：

Deazathiamine; 3-Deazathiaminediphosphate; 3-Deazathiamine; 3-Deazathiamine synthesis; 2,3,5-Tribromo-3-methylthiophene; THIAMINE PYROPHOSPHATE; DEPENDENT ENZYMES; GENE-REGULATION; ANALOGS; DIPHOSPHATE; DERIVATIVES; TUBERCULOSIS; RIBOSWITCH; RNA;

D O I：

10.1016/j.bmcl.2010.09.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery of 3-deazathiamine diphosphate (deazaThDP) as a potent inhibitor analog of the cofactor thiamine diphosphate (ThDP) has highlighted the need for an efficient and scalable synthesis of deazaThDP. Such a method would facilitate development of analogs with the ability to inhibit individual ThDP-dependent enzymes selectively. Toward the goal of developing selective inhibitors of the mycobacterial enzyme 2-hydroxy-3-oxoadipate synthase (HOAS), we report an improved synthesis of deazaThDP without use of protecting groups. Tribromo-3-methylthiophene served as a versatile starting material whose selective functionalization permitted access to deazaThDP in five steps, with potential to make other analogs accessible in substantial amounts. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6472 / 6474

页数：3

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