收回:用于合成多种乳酸的选择性酶C−H化
Inha Cho1, Zhi-Jun Jia1, Frances H Arnold2
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
概括
工程酶精确地控制碳-键反应,使各种乳结构的选择性合成成为可能. 这一突破为各种应用提供了高效和高度选择性的碳键形成.
科学领域:
- 生物催化
- 有机化学
- 酶工程
背景情况:
- 碳- (C-H) 键的功能化在化学中至关重要.
- 控制C-H激活的选择性仍然是一个重大挑战.
- 细胞P450酶具有选择性催化潜力.
研究的目的:
- 为了对细胞P450酶进行反选择性C-H化.
- 在乳合成中实现精确的位点选择性,超过固有的C-H反应性.
- 开发一种有效且可扩展的非生物碳键形成方法.
主要方法:
- 细胞P450酶的工程.
- 在大肠杆菌中表达工程酶.
- 使用自然启发的乙烯基保护酸盐前体来产生碳酸.
主要成果:
- 取得了前所未有的C-H选择性化反应.
- 通过构建β,γ和δ乳酸体,对位点选择性的精确控制.
- 观察到高效率 (高达1,020,000个总周转率) 和选择性 (高达25:1的区域选择性,97%.
- 在准备规模上成功进行了转换.
结论:
- 工程P450酶可以精确地控制C-H功能.
- 这种方法可使各种乳结构的分离合成具有高选择性.
- 开发的生物催化方法是高效的,可扩展的,并为生物C-N键形成提供了强大的工具.
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