通过由工程化细胞染色体P450酶催化的碳转移进行烯环化
Pedro S Coelho1, Eric M Brustad, Arvind Kannan
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Science (New York, N.Y.)
|December 22, 2012
概括
研究人员设计了细胞P450酶来执行碳转移反应,从而使循环 styrenes 的合成. 这一突破为自然界以前未知的关键有机合成反应创造了一种生物方法.
科学领域:
- 生物催化剂是一种生物催化剂.
- 有机合成 有机合成
- 酵素工程是什么意思 酵素工程
背景情况:
- 过渡金属催化剂对于通过碳,烯和氧基转移使C=C和C-H键发挥作用至关重要.
- 细胞染色体P450酶是自然界对氧基转移的催化剂,但没有观察到生物碳转移到烯.
- 碳转移到烯酸是合成有机化学中关键的C-C键形成反应.
研究的目的:
- 为了设计能够催化碳转移反应的细胞染色体P450的变体.
- 通过使用工程酶,实现对 styrenes 的高度二选择性和选择性循环化.
- 为了证明自然酶对自然中缺少的合成相关反应的适应性.
主要方法:
- 细胞染色体P450的蛋白质工程 (((BM3) 变体.
- 使用二氧化试剂的循环化反应的催化.
- 循环产品的立体化学分析.
主要成果:
- 改造的细胞染色体P450 (BM3) 变体成功催化了碳转移到烯.
- 酶性循环化过程具有较高的二选择性和反选择性.
- 为工程酶提出了假设的碳转移机制.
结论:
- 酶工程可以将P450s等自然酶适应新型合成转化.
- 这项工作建立了一个生物催化路径,用于酶选择性循环化,这是有机合成中的关键反应.
- 工程P450s为传统的金属催化剂提供了一个可持续和选择性的替代品,用于碳转移.
相关概念视频
01:16Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
01:26Thermal and Photochemical Electrocyclic Reactions: Overview
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Introduction
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
01:26Photochemical Electrocyclic Reactions: Stereochemistry
The absorption of UV–visible light by conjugated systems causes the promotion of an electron from the ground state to the excited state. Consequently, photochemical electrocyclic reactions proceed via the excited-state HOMO rather than the ground-state HOMO. Since the ground- and excited-state HOMOs have different symmetries, the stereochemical outcome of electrocyclic reactions depends on the mode of activation; i.e., thermal or photochemical.
Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation
01:17Pericyclic Reactions: Introduction
Pericyclic reactions are organic reactions that occur via a concerted mechanism without generating any intermediates. The reactions proceed through the movement of electrons in a closed loop to form a cyclic transition state, where rearrangement of the σ and π bonds yields specific products.
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic rearrangements are...
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic rearrangements are...