キラルフォスフィナートエステルの酵素分解
Yingchun Li1, Sarah D Aubert, Eugene G Maes
1Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, USA.
Journal of the American Chemical Society
|July 22, 2004
まとめ
細菌のフォスフォートリエステラーゼ酵素は,フォスフィナートエステルのステレオ選択的水解を示します. 変異した酵素が野生型の選択性を逆転させ,キラルフォスフィンと酸化物の化学酵素合成を可能にします.
科学分野:
- バイオケミストリー バイオケミストリー
- 酵素学 酵素学とは
- 有機化学 オーガニック・ケミストリー
背景:
- 細菌のフォスフォートリエステラーゼ (Bpt) 酵素は,その触媒活性で知られている.
- リン酸塩エステルのステレオ選択的水解は,合成化学における重要な反応である.
研究 の 目的:
- フォスフィナートエステルに対する野生型および変異性細菌のフォスフォトトリエステラーゼのステレオ選択性を調査する.
- 化学酵素合成におけるエナチオメリックに純粋なフォスフィナートエステルの可能性を調査する.
主な方法:
- 野生型および変異型Bpt.を使用したラセミック・フォスフィナートエステルの運動解像度.
- エナティオメリカルに純粋なフォスフィナートエステルの調製.
- P-キラルフォスフィンとフォスフィン酸化物の化学酵素合成.
主要な成果:
- 野生型Bptは,メチルフェニルp-X-フェニルフォスフィナートエステルのSP-エナントイオマーを好ましく水解する.
- 特定の変異酵素 (I106T/F132A/H254G/H257W) は,逆のステレオ選択性を示し,RP-エナティオメアを好む.
- 変異した酵素は,RP-エナチオメールの水解速度を大幅に高めています.
結論:
- バクテリアのフォスフォートリエステラーゼは,フォスフィナートエステル水解における変化したステレオ選択性のために設計することができます.
- 酵素的運動分解によって生成されるエナチオメリックに純粋なフォスフィナートエステルは,キラル有機リン化合物の貴重な前駆体である.
関連する概念動画
Enzyme Inhibition
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
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:
Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis
Hydrolysis of esters under acidic conditions proceeds through a nucleophilic acyl substitution. In the presence of excess water, the reaction proceeds in a reversible manner, forming carboxylic acids and alcohols.
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
Reactivity of Enols
Enols are a class of compounds where a hydroxyl group is attached to a carbon–carbon double bond, which implies that it is a vinyl alcohol. A carbonyl compound with an α hydrogen undergoes keto–enol tautomerism and remains in equilibrium with its tautomer, the enol form. Usually, the keto tautomer is present in a higher concentration than the enol tautomer due to the higher bond energy of C=O compared to C=C. Moreover, the direction of the keto–enol equilibrium is governed by factors like...
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.
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
Carboxylic acids react with alcohols to yield esters via an acid-catalyzed condensation reaction called Fischer esterification. This is a nucleophilic acyl substitution reaction that proceeds via a tetrahedral intermediate, where a water molecule is eliminated as the leaving group.


