由酶控制的原子转移使区域分离的C-H氨基化成为可能
Todd K Hyster1, Christopher C Farwell, Andrew R Buller
1Division of Chemistry and Chemical Engineering 210-41, California Institute of Technology , 1200 East California Boulevard, Pasadena, California 91125, United States.
工程化细胞染色体P450BM3 (CYP102A1) 变体实现了选择性的C-H氨基化. 这些催化剂控制区域选择性,指导插入到基或同基C-H键.
科学领域:
- 生物催化剂是一种生物催化剂.
- 有机化学 有机化学
- 酵素工程是什么意思 酵素工程
背景情况:
- 细胞染色体P450BM3 (CYP102A1) 变体催化C-H氨基化,形成新的C-N键.
- 在C-H氨基化中实现催化剂控制的区域选择性仍然是一个重大挑战.
研究的目的:
- 为了设计P450BM3变体,对C-H氨基化具有不同的区域选择性.
- 研究C-H氨基化中催化剂控制的区域选择性的机制.
主要方法:
- 在P450BM3变体的蛋白质工程.
- C-H 氨基化试验.
- 运动同位素效应测量.
- 在X射线晶体学 (2.66 Å分辨率).
主要成果:
- 两种工程P450BM3变体显示出不同的区域选择性.
- 一种变种偏爱基C-H氨基化,另一种偏爱 homo-benzylic C-H氨基化.
- 几乎相同的动态同位素效应值 (2.8-3.0) 表明限制速度的C-H抽象.
- 晶体结构表明工程活动部位预先组织了基质以进行反应.
结论:
- 设计的P450BM3变体可以控制C-H氨基化中的区域选择性.
- 酶活性部位工程是实现选择性C-H功能化的可行策略.
- 区域选择性很可能是由C-H键在铁化物附近的精确定位控制的.
更多相关视频
12:31Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry
Published on: August 19, 2012
07:30A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones
Published on: January 21, 2020
相关概念视频
Preparation of Amines: Reductive Amination of Aldehydes and Ketones
Nucleophilic Aromatic Substitution: Elimination–Addition
Electrophilic Aromatic Substitution: Nitration of Benzene
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Preparation of Amines: Reduction of Oximes and Nitro Compounds
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
