氨基酸的非对称α-arylation
Daniel J Leonard1, John W Ward1, Jonathan Clayden2
1School of Chemistry, University of Bristol, Bristol, UK.
Nature
|October 5, 2018
概括
现在可以在不损失立体化学完整性的情况下合成四级α-氨基酸. 这种新方法使用易于获得的氨基酸,避免了昂贵的过渡金属,使得多克的生产成为可能.
科学领域:
- 有机化学
- 医学化学
- 合成化学
背景情况:
- 四级氨基酸对于改变结构和生物活性至关重要.
- 在合成上具有挑战性,氨基酸的酶选择性α-化是制造有价值的生物活性分子的关键.
- 已有可用于化的方法,但在α-碳的一般化仍然很困难.
研究的目的:
- 开发一种实用且可扩展的合成四级α-氨基酸的方法.
- 在不损害立体化学完整性的情况下实现氨基酸前体的酶选择性α-化.
- 通过使用易于获得的原料来合成各种α-aryl氨基酸.
主要方法:
- 用于α-arylation的纯氨基酸前体.
- 采用了一种策略,包括在一种伊米达佐利丁衍生物的N'-arylurea添加物中临时形成第二个立体中心.
- 在合成过程中避免使用过渡金属.
主要成果:
- 从具有高立体化学完整性的纯原体成功合成了四级α-氨基酸.
- 与广泛的替代物,包括电子丰富的,电子贫乏的和异环群的证明.
- 展示了从单个前体中生产产品的任何一个体的能力,并可扩展到多克的数量.
结论:
- 开发了一种新的,实用的,可扩展的四级α-aryl氨基酸的合成方法.
- 这种方法提供了一条有价值的途径,以获得各种α-结氨基酸,这是药物化学的重要前体.
- 这种方法克服了以前的合成限制,提供了无过渡金属的复杂氨基酸衍生物.
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