用铜催化直接合成硫胺的三组分
Yiding Chen1, Philip R D Murray1, Alyn T Davies1
1Department of Chemistry, Chemistry Research Laboratory , University of Oxford , Mansfield Road , Oxford OX1 3TA , United Kingdom.
Journal of the American Chemical Society
|July 3, 2018
概括
这项研究引入了一种新的,单步合成硫胺,这是药物中关键的功能组. 该方法有效地结合了现有的构建块,为硫胺药物发现提供了一种多功能方法.
科学领域:
- 有机化学
- 医学化学
- 催化剂
背景情况:
- 自20世纪30年代以来,硫胺在制药和农业化学品中起到了至关重要的作用.
- 目前的硫胺合成方法基本没有变化,需要预先安装的硫功能.
- 这限制了创造多样化的硫胺结构的范围和效率.
研究的目的:
- 开发一种直接的,单步合成广泛的硫胺.
- 使用易于获得的原料,包括酸和氨基.
- 建立适用于药物发现和开发的多功能方法.
主要方法:
- 使用铜 (II) 催化剂直接合 (异) 酸和氨基.
- 通过代用试剂DABSO提供使用的二氧化硫.
- 研究了该反应对各种基,异基,基和基胺合伙伴的耐受性.
主要成果:
- 在单个步骤中实现了硫胺的广泛合成.
- 与各种酸 (基,异基,基) 和氨基 (循环,非循环,基) 证明了相容性.
- 成功地将药物碎片和各种药物构建块纳入反应.
结论:
- 报告的方法提供了一种高效和多用途的硫胺途径.
- 这种进步简化了硫胺的合成,使其在药物发现中得到更广泛的应用.
- 直接合方法扩大了可用于新生物活性分子设计的化学空间.
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