Efficient Access to New Chemical Space Through Flow-Construction of Druglike Macrocycles Through Copper-Surface-Catalyzed Azide-Alkyne Cycloaddition Reactions
Efficient Access to New Chemical Space Through Flow-Construction of Druglike Macrocycles Through Copper-Surface-Catalyzed Azide-Alkyne Cycloaddition Reactions
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DOI：
10.1002/chem.201002215
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
James, Keith
中科院分区：
文献类型：
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作者：
Bogdan, Andrew R.;James, Keith
利用铜催化的叠氮化物-乙炔环加成反应，在环境友好的条件下，在高温铜管中流动进行，生成了一系列具有类似药物的功能和性质的12-22元大环。含有三氮唑的大环在5分钟的反应中以高达90%的产率生成，而不需要借助典型的大环反应的高稀释条件。就产率、浓度和环境因素而言，这种方法代表了一种非常有效的方法来构建这类重要的分子。
A series of 12- to 22-membered macrocycles, with druglike functionality and properties, have been generated by using a simple and efficient copper-catalyzed azide-acetylene cycloaddition reaction, conducted in flow in high-temperature copper tubing, under environmentally friendly conditions. The triazole-containing macrocycles have been generated in up to 90% yield in a 5 min reaction, without resorting to the high-dilution conditions typical of macrocyclization reactions. This approach represents a very efficient method for constructing this important class of molecules, in terms of yield, concentration, and environmental considerations.