A protecting group-free synthesis of deazathiamine: A step toward inhibitor design Journal Article
| Authors: | Zhao, H.; de Carvalho, L. P. S.; Nathan, C.; Ouerfelli, O. |
| Article Title: | A protecting group-free synthesis of deazathiamine: A step toward inhibitor design |
| Abstract: | 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. © 2010 Elsevier Ltd. All rights reserved. |
| Keywords: | unclassified drug; drug structure; in vitro study; drug synthesis; antiinfective agent; ic 50; pyrimidine; carbon nuclear magnetic resonance; 2 hydroxy 3 oxoadipate synthase; bacterial enzyme; antimicrobial activity; 2,3,5-tribromo-3-methylthiophene; 3-deazathiamine; 3-deazathiamine synthesis; 3-deazathiaminediphosphate; deazathiamine; 3 deazathiamine; 3 deazathiamine diphosphate |
| Journal Title: | Bioorganic & Medicinal Chemistry Letters |
| Volume: | 20 |
| Issue: | 22 |
| ISSN: | 0960-894X |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2010-11-15 |
| Start Page: | 6472 |
| End Page: | 6474 |
| Language: | English |
| DOI: | 10.1016/j.bmcl.2010.09.053 |
| PROVIDER: | scopus |
| PUBMED: | 20943392 |
| PMCID: | PMC2957563 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: BMCLE" - "Source: Scopus" |
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