Divergent Strategy for the Synthesis of -Aryl-Substituted Fosmidomycin Analogues

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• 作者：Vincent Devreux ; Jochen Wiesner ; Hassan Jomaa ; Jef Rozenski ; Johan Van der Eycken ; Serge Van Calenbergh
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：May 11, 2007
• 年：2007
• 卷：72
• 期：10
• 页码：3783 - 3789
• 全文大小：131K
• 年卷期：v.72,no.10(May 11, 2007)
• ISSN：1520-6904

文摘

Fosmidomycin is the first representative of a new class of antimalarial drugs acting through inhibition of1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway for the synthesis of isoprenoids. This work describes a divergent strategy for thesynthesis of a series of DER=0>-aryl-substituted fosmidomycin analogues, featuring a palladium-catalyzed Stillecoupling as the key step. An -(4-cyanophenyl)fosmidomycin analogue emerged as the most potentanalogue in the present series. Its antimalarial activity clearly surpasses that of the reference compoundfosmidomycin.