オーガノボロン酸残留を含む人工フリーデルクラフトアルキル化酵素の設計と進化
Shu-Bin Mou1, Kai-Yue Chen1, Thittaya Kunthic1
1State Key Laboratory of Chemical Oncogenomics, Shenzhen Key Laboratory of Chemical Genomics, AI for Science (AI4S) Preferred Program, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. China.
Journal of the American Chemical Society
|August 27, 2024
まとめ
研究者は新しいアミノ酸を用いて 人工酵素を設計した. この酵素は効率的に炭素-炭素結合を作り,複雑なスパイロインデリン化合物の合成を可能にします.
科学分野:
- 生物化学
- 合成生物学
- 有機化学
背景:
- 自然の酵素は 触媒の多様性には 限界があります
- 非正規のアミノ酸の遺伝的組み込みは酵素の能力を拡張することができます.
- 人工酵素は新しい化学的変化をもたらします
研究 の 目的:
- 触媒機能を拡張した 新しい人工酵素を設計し 作る
- 合成酵素の触媒残基としてp-ボロノフェニララニンを利用する.
- 準備スケールの合成のための全細胞触媒法を開発する.
主な方法:
- 酵素にp-ボロノフェニララニンの遺伝子組み換え
- 酵素を設計して 高い生産性とエナチオセレクティブ性
- マイケル型フリーデル・クラフトスアルキル化のための全細胞触媒.
- 酵素反応とパラジアム触媒による脱オロマティブアリレーションを組み合わせる.
主要な成果:
- P-ボロフェニララニンを利用した人工酵素を成功裏に設計した.
- この酵素は,コバルント活性化によるマイケル型フリーデル=クラフトアルキル化を触媒とした.
- エンジニアリングされた酵素は高収量と優れたエナチオ選択性を達成した.
- 準備スケールの実用的な全細胞触媒法を開発した.
- スピロインドレニン化合物の効率的な合成を達成した.
結論:
- 非正規のアミノ酸を含む人工酵素は,触媒的可能性を大幅に拡大する.
- 開発された人工酵素は,C-C結合形成のための新しい経路を提供します.
- スピロインドレーニンのような複雑な分子を 合成するための実用的なアプローチを 提供しています
関連する概念動画
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
17.9K
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
17.9K
01:17Electrophilic Aromatic Substitution: Friedel–Crafts Alkylation of Benzene
6.5K
Friedel–Crafts reactions were developed in 1877 by the French chemist Charles Friedel and the American chemist James Crafts. Friedel–Crafts alkylation refers to the replacement of an aromatic proton with an alkyl group via electrophilic aromatic substitution. A Lewis acid catalyst such as aluminum chloride reacts with an alkyl halide to form a carbocation. The resulting carbocation then reacts with the aromatic ring and undergoes a series of electron rearrangements before giving the...
6.5K
01:26Limitations of Friedel–Crafts Reactions
5.3K
Several restrictions limit the use of Friedel–Crafts reactions. First, the halogen in the alkyl halide must be attached to an sp3-hybridized carbon for the Friedel–Crafts reactions to occur. Vinyl or aryl halides do not react since the carbocations formed are unstable under the reaction conditions. Second, Friedel–Crafts alkylation is susceptible to carbocation rearrangement, and the major products obtained have a rearranged carbon skeleton. In contrast, the acylium ion is...
5.3K
03:08Hydroboration-Oxidation of Alkenes
8.0K
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
8.0K
01:11Electrophilic Aromatic Substitution: Friedel–Crafts Acylation of Benzene
7.0K
The Friedel–Crafts acylation reactions involve the addition of an acyl group to an aromatic ring. These reactions proceed via electrophilic aromatic substitution by employing an acyl chloride and a Lewis acid catalyst such as aluminum chloride to form aryl ketone.
7.0K
01:13Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
7.8K
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.
7.8K