A method for the rapid synthesis of benzopyrone libraries employing a resin capture strategy.
A method for the rapid synthesis of benzopyrone libraries employing a resin capture strategy.
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一种采用树脂捕获策略快速合成苯并吡喃酮库的方法。
DOI：
10.1021/cc000042j
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Brueggemeier,RW
中科院分区：
文献类型：
--
作者：
Bhat,AS;Whetstone,JL;Brueggemeier,RW
The benzopyrone ring system is present in a number of natural products, including flavonoids, that interact with various enzymes and receptors of pharmacological significance. This ring system can serve as an important scaffold for developing novel small molecule therapeutic agents for the emerging molecular targets in breast and prostate cancer. We are interested in the construction and screening of combinatorial libraries focused on the benzopyrone ring system, with an aim to develop novel anticancer agents. Although there are numerous literature methods for synthesis of the benzopyrone ring system, they are not ideally suited for combinatorial approaches due to harsh reaction conditions, poor yields, and limited substituent tolerance. 1 In a recent communication we described a novel synthetic approach, suitable for constructing benzopyrone combinatorial libraries by solution phase chemistry. 2 We effected a onepot conversion of bis-silylated salicylic acids into alkynyl ketones via an acid chlorination and subsequent Sonogashira coupling with terminal alkynes. The alkynyl ketones were treated with secondary amines to form enaminones, which underwent a facile cyclization and elimination of secondary amine to provide the benzopyrone nucleus (Figure 1). This method uses readily available starting materials in mild and high yielding reactions that display a high substituent tolerance and, therefore, is ideally suited for rapid synthesis of diverse libraries. Since our initial report, two recent papers have described efforts in constructing benzopyrone libraries, thus underscoring the importance of this scaffold in lead discovery. 3
