Development of novel LpxC inhibitors: chiral-pool synthesis of?C-triazolyl glycosides
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- 作者：Sunit Kumar Jana ; Marius L?ppenberg ; Constantin G. Daniliuc ; Joachim Jose ; Ralph Holl
- 关键词：LpxC inhibitors ; C-Aryl furanosides ; Click chemistry ; Triazoles ; Chiral pool synthesis ; Stereoselective synthesis
- 刊名：Tetrahedron
- 出版年：2013
- 出版时间：11 November, 2013
- 年：2013
- 卷：69
- 期：45
- 页码：9434-9442
- 全文大小：771 K
文摘
The Zn2+-dependent deacetylase LpxC plays an important role in the biosynthesis of the cell wall of Gram-negative bacteria and therefore represents an interesting target for the development of novel antibiotics. In a 10-step, chiral pool synthesis starting from d-mannose (3), a series of C-aryl furanosidic hydroxamic acids bearing a 1,4-disubstituted triazole ring in ¦Á-configuration at the furanose moiety was stereoselectively synthesized and tested for inhibitory activity against LpxC. The key step of the synthesis comprises a Cu(I) catalyzed Huisgen cycloaddition of terminal alkyne 10 with various azides to introduce diversity to the potential LpxC inhibitors. The X-ray crystal structure of the click product 11e proves the stereochemistry at the anomeric center and the substitution pattern of the triazole ring. The synthesized compounds did not inhibit LpxC.