キニンとキニジンの触媒的非対称総合成
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
まとめ
研究者は,キニンとキニジンの16段階の触媒的非対称合成を開発しました. 主なステップには,ステレオセンター制御のためのサラン (((Al)) 触媒化されたマイケルの添加と,ダイアステロエーマー分化のための非対称性ダイヒドロキシル化が含まれています.
科学分野:
- 有機化学 オーガニック・ケミストリー
- アシンメトリック・シンセシス
- 薬用化学 薬用化学について
背景:
- キニンとキニジンは,複雑なステレオ化学を備えた重要な抗マラリア薬である.
- 効率的で選択的な合成経路は,その生産とアナログ開発に不可欠です.
研究 の 目的:
- キニンとキニジンの両方の触媒的,非対称な合成を確立する.
- 精密なステレオ化学制御のための新しい触媒的方法を使用する.
主な方法:
- 16段階の合成シーケンスが採用されました.
- メチルシアノアセタートの付加により,C4ステレオセンター (92% ee) が確立されました.
- 後期段階の非対称性ダイヒドロキシル化は,ダイアステロエーマーを生成する中介物質を微分化しました.
主要な成果:
- キニンとキニジンの触媒的非対称合成が成功しました.
- 重要なマイケルの追加ステップで高いエナチオセレクティブ性 (92% ee) が得られた.
- 高度なダイアステロ選択性は,後期的なダイヒドロキシル化において観察された.
結論:
- 開発された合成戦略は,キニンとキニジンへの効率的な経路を提供します.
- 採用された触媒的方法は,ステレオ化学を正確に制御することができます.
- このアプローチは,これらの重要な医薬品化合物へのアクセスを容易にします.
さらに関連する動画
関連する概念動画
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.


