具有潜在DNA解旋酶B及热休克蛋白90抑制活性的4-去羟基氯新生霉素类似物的合成

doi:10.5246/jcps.2011.03.027

具有潜在DNA解旋酶B及热休克蛋白90抑制活性的4-去羟基氯新生霉素类似物的合成

何奕秋, 李永强, 马良, 俞晓明^*

中国医学科学院药物研究所, 北京 100050

收稿日期:2011-01-07 修回日期:2011-03-25 出版日期:2011-05-06 发布日期:2011-05-06
通讯作者: 俞晓明*

Synthesis of 4-des-hydroxyl clorobiocin analogues as possible bacterial DNA gyrase B and human Hsp90 inhibitors

Yi-Qiu He, Yong-Qiang Li, Liang Ma, Xiao-Ming Yu^*

Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China

Received:2011-01-07 Revised:2011-03-25 Online:2011-05-06 Published:2011-05-06
Contact: Xiao-Ming Yu*

摘要/Abstract

摘要：

氨基香豆素类抗生素系一类兼具细菌DNA解旋酶B (DNA gyrase B) 和人体热休克蛋白90 (Hsp90) 抑制活性的天然产物。因缺乏有效的合成手段, 有关此类化合物的构效关系信息非常有限。本文首次详细探讨了3-O-酰化L-诺维糖的从头合成方法, 并最后完成了一系列4-去羟基氯新生霉素类似物的合成, 为氨基香豆素类化合物的合成提供了一套可行的化学合成路线。该路线的扩展应用将有助于氨基香豆素类化合物构效关系研究的进一步深入。

关键词: 氯新生霉素, 4-去羟基类似物, 合成

Abstract:

Aminocoumarin natural products are known as inhibitors of both bacterial DNA gyrase B and human Hsp90. Due to the lack of efficient synthetic approach, structure activity relationship (SAR) understandings of these molecules are still limited. Synthesis of a set of novel 4-des-hydroxyl clorobiocin analogues, including the de novo construction of properly functionalized L-noviose building blocks and the subsequent assembly of the target molecules, is described in full detail. Expanded application of this synthetic protocol is expected to help gaining more information about the SAR of aminocoumarins.

Key words: Clorobiocin, 4-Des-hydroxyl analogue, Synthesis

中图分类号:

R916

Supporting:

Foundation item: National Natural Science Foundation (Grant No. 30772634).
^*Corresponding author. Tel.: 86-10-63165259

何奕秋, 李永强, 马良, 俞晓明^*. 具有潜在DNA解旋酶B及热休克蛋白90抑制活性的4-去羟基氯新生霉素类似物的合成[J]. , DOI: 10.5246/jcps.2011.03.027.

Yi-Qiu He, Yong-Qiang Li, Liang Ma, Xiao-Ming Yu^* . Synthesis of 4-des-hydroxyl clorobiocin analogues as possible bacterial DNA gyrase B and human Hsp90 inhibitors [J]. , DOI: 10.5246/jcps.2011.03.027.

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