催化不对称的氨酸和氨酸的总合成
Izzat T Raheem1, Steven N Goodman, Eric N Jacobsen
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Journal of the American Chemical Society
|January 22, 2004
概括
研究人员开发了一种16步的催化不对称合成和胺. 关键步骤包括salen ((Al) 催化迈克尔添加用于立体中心控制和非对称二氧化二氧化物用于二氧化物分化.
科学领域:
- 有机化学 有机化学
- 不对称的合成方法
- 药用化学 医学化学
背景情况:
- 氨酸和氨酸是具有复杂立体化学的重要抗疟药物.
- 有效和选择性的合成路线对于它们的生产和模拟开发至关重要.
研究的目的:
- 为了建立一个催化,不对称的合成和丁.
- 用新的催化方法来实现精确的立体化学控制.
主要方法:
- 采用了一个16步合成序列.
- 盐 ((Al) 催化酶的反选择性迈克尔添加甲基酸建立了C4立体中心 (92% ee).
- 晚期不对称的二基化分化中间体,产生二聚体.
主要成果:
- 成功实现了因和因丁的催化不对称合成.
- 在关键的迈克尔添加步骤中获得了高的酶选择性 (92% ee).
- 在后期的二基化过程中观察到高的二基选择性.
结论:
- 开发的合成策略提供了一条有效的通往氨酸和氨酸的途径.
- 使用的催化方法可以精确控制立体化学.
- 这种方法可以更容易地获得这些重要的药物化合物.
相关概念视频
Catalysis
The presence of a catalyst affects the rate of a chemical reaction. A catalyst is a substance that can increase the reaction rate without being consumed during the process. A basic comprehension of a catalysts’ role during chemical reactions can be understood from the concept of reaction mechanisms and energy diagrams.
Aldehydes and Ketones with Alcohols: Hemiacetal Formation
Similar to water, alcohols can add to the carbonyl carbon of the aldehydes and ketones. The addition of one molecule of alcohol to the carbonyl compound forms the hemiacetal or half acetal. As depicted below, in a hemiacetal, the carbon is directly linked to an OH and OR group.
Acid Halides to Esters: Alcoholysis
Alcoholysis is a nucleophilic acyl substitution reaction in which an alcohol functions as a nucleophile. Acid halides react with alcohol to produce esters. The mechanism proceeds in three steps:
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Acid-Catalyzed Aldol Addition Reaction
The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The acid-catalyzed aldol reaction is depicted in Figure 1.
Aldol Condensation vs Claisen Condensation
Aldol condensation is an acid or base-catalyzed condensation between aldehydes or ketones to give an α,ꞵ-unsaturated carbonyl compound. A base-promoted condensation between ester molecules to produce a ꞵ-ketoester is known as the Claisen condensation. In the presence of a base, both reactions involve deprotonation of the acidic α hydrogen to produce the corresponding enolates. The nucleophilic enolates attack their respective nonenolized carbonyl compound forming a tetrahedral intermediate.


