生物催化 2-Arylindoles 的立体选择性氧化
Sarah E Champagne1,2, Chang-Hwa Chiang1,2, Philipp M Gemmel1
1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
Journal of the American Chemical Society
|January 18, 2024
概括
研究人员开发了一种不对称的生物催化氧化方法,使用黄素依赖单氧酶 (FDMOs) 合成3-氨基烯酸. 一种新兴的酶,香酶,通过立体选择性地产生了这些具有高反体过量的有价值的化合物.
科学领域:
- 生物催化
- 有机化学
- 酵素学
背景情况:
- 在天然产品和药品中,3-二烯酸是关键的结构基因.
- 传统的3-二氨酸化学合成面临过度氧化和复杂产品混合等挑战.
- 酶反应具有很高的选择性,可以克服合成障碍并产生富含的产品.
研究的目的:
- 开发一种高效的不对称生物催化氧化方法来合成3-二烯.
- 识别和描述能够进行立体选择性内醇氧化的新酶.
- 在获取有价值的化学支架时探索工程制造的黄素依赖单氧酶 (FDMOs).
主要方法:
- 使用祖先序列空间,序列相似性网络和深度学习开发的黄素依赖单氧酶 (FDMOs) 的策划库.
- 选FDMO图书馆对2-arylindole基质的不对称氧化.
- 确定酶的基质范围和立体选择性的特征.
- 优化反应条件的产量和反体比 (er).
主要成果:
- 一种以前未被描述的FDMO,名为Champase,来自*Coccidioides immitis*.
- 香在氧化各种替代的2 - 亚林多尔到3 - 英多林的过程中表现出高的立体选择性.
- 该酶获得了中等到优异的产量和高达95: 5的反体比.
- 这项研究展示了该酶在一系列的基质中的杂交性.
结论:
- 使用工程化FDMOs,特别是Champase的不对称生物催化氧化提供了一种有效的途径,以获得富含的3-氨.
- 香是一种新型的生物催化剂,用于有价值的药物中间体的立体选择合成.
- 这种方法克服了传统化学合成的局限性,提供了更环保,更有选择性的替代方案.
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