对α,β-非替代β-氨基酸的酶选择性合成
Mukund P Sibi1, Prabagaran Narayanasamy, Sandeep G Ghorpade
1Department of Chemistry, North Dakota State University, Fargo, North Dakota 58105, USA.
Journal of the American Chemical Society
|September 25, 2003
概括
这项研究引入了一种新方法,用于使用催化剂从伊米德合成奇拉性异索利丁. 由此产生的化合物可以转化为有价值的β-氨基酸.
科学领域:
- 有机化学 有机化学
- 不对称的合成方法
- 催化剂是一种催化剂.
背景情况:
- 基拉尔β-氨基酸是药品中重要的构建基.
- 开发高效的合成方法至关重要.
研究的目的:
- 开发一种高度分离选择和分离选择的方法,用于合成α,β-转换异位的N-基氧化丁.
- 探索这些异二丁直接转化为有价值的β-氨基酸.
主要方法:
- 将N-基氧胺添加到由Mg ((NTf2) 2) 和接体18催化的伊米德中.
- 由此产生的异xazolidinones的解.
主要成果:
- 实现了高的二选择性 (93-99% de) 和反选择性 (60-96% ee).
- 成功合成了α,β-转换异位的N-基氧化丁.
- 已证明直接转化为α,β-非替代β-氨基酸.
结论:
- 开发的催化系统提供了一个有效的途径,以奇拉性isoxazolidinones.
- 这种方法提供了一条直接的途径,可以获得有价值的性β-氨基酸衍生物.
相关概念视频
Reactions of Aldehydes and Ketones: Baeyer–Villiger Oxidation
Baeyer–Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often catalyzed by acid. The reaction is named after its pioneers, Adolf von Baeyer and Victor Villiger. The reaction is achieved by a wide range of peracids such as m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid (C6H5COOOH), peracetic acid (CH3COOOH), hydrogen peroxide (H2O2), and tert-butyl hydroperoxide (t-BuOOH).
The carbonyl center is activated by...
The carbonyl center is activated by...
Regioselective Formation of Enolates
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are more stable. But the energy required to form kinetic enolates is less.
Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in the molecule leads to three resonance structures. The hybrid form exhibits two probable electrophilic sites: the carbonyl carbon and the β carbon.
Factors Affecting α-Alkylation of Ketones: Choice of Base
α-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed by nucleophilic substitution. The choice of base employed is essential as it is the key factor in determining the reaction outcome.
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence, side reactions...
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence, side reactions...
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.


