光駆動による酵素エナチオセレクティブ・ラジカルアサイレーション
Yuanyuan Xu1, Hongwei Chen1, Lu Yu2
1State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
Nature
|December 19, 2023
まとめ
この研究は,非対称な基質変換のためのチアミン二酸化物 (ThDP) 依存酵素を再利用し,新しい二重生物触媒と光触媒のアプローチを使用して,アルデヒドからキラルケトンを生成します.
科学分野:
- 生物触媒
- 有機化学
- 酵素工学
背景:
- 酵素はステレオ選択的触媒に優れているが 激素反応の制御は化学的方法に遅れている.
- チアミン二酸化物 (ThDP) に依存する酵素は,N-ヘテロサイクリックカルベン (NHC) を誘発したが,非対称的な基質反応では使用されていない.
- バイオコンパティブルなラジカル生成は,生物学的システムがしばしば反応性ラジカルを避けるため,制限されています.
研究 の 目的:
- ステレオセレクティブのラジカルアシル移転のためのThDP依存酵素を設計する.
- 一般的で生物互換性の高い非対称的な基質変換法を開発する.
- バイオカタリシスとオルガノフォテロドックスカタリシスを併用して 根幹を抑制する.
主な方法:
- ThDP依存型ライアゼをラジカルアシルトランスファーゼ (RAT) に変換するタンパク質工学.
- 酵素に結合したThDP由来ケチルラジカルを生成するために,オルガノフォテロドックス触媒を用いる.
- ケチルラジカルとプロキラルアルキルラジカルをクロスカップリングして非対称な合成を行う.
主要な成果:
- ThDP依存酵素をステレオセレクティブラジカルアシルトランスファーゼ (RAT) として再利用しました.
- 高いエナチオ選択性 (最大97%e.e.) アルデヒドから様々なキラルケトンを合成する.
- 新しい二重酵素触媒/光触媒の戦略が示された.
結論:
- バイオカタリシスの範囲を非対称な基質化学に拡張した.
- 反応性急性素を制御する 独特の酵素戦略を提供した
- キラル合成のための既存の化学的方法の補完的なツールを開発しました.
関連する概念動画
Radical Anti-Markovnikov Addition to Alkenes: Overview
3.4K
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.
3.4K
Radical Reactivity: Nucleophilic Radicals
2.1K
Radicals adjacent to electron-donating groups are called nucleophilic radicals. These radicals readily react with electrophilic alkenes. The SOMO–LUMO interactions are the driving force for the reaction, where the high-energy SOMO of the electron-rich, nucleophilic radicals interacts with the low-energy LUMO of the electron-deficient, electrophilic alkenes. Such SOMO–LUMO interactions are the basis of reactive radical traps, affecting the selectivity in radical reactions. For...
2.1K
Radical Reactivity: Electrophilic Radicals
1.9K
Radicals adjacent to electron‐withdrawing groups are called electrophilic radicals. These radicals readily react with nucleophilic alkenes. For example, the malonate radical, in which the radical center is flanked by two electron‐withdrawing groups, reacts readily with butyl vinyl ether, which consists of an electron‐donating oxygen substituent. The reaction between electrophilic malonate radical and nucleophilic vinyl ether is favored because the radical has a...
1.9K
Sharpless Epoxidation
4.0K
The conversion of allylic alcohols into epoxides using the chiral catalyst was discovered by K. Barry Sharpless and is known as Sharpless epoxidation. The use of a chiral catalyst enables the formation of one enantiomer of the product in excess. This chiral catalyst is mainly a chiral complex of titanium tetraisopropoxide and tartrate ester (specific stereoisomer). The stereoisomer used in the chiral catalyst dictates the formation of the enantiomer of the product. In other words, the use of...
4.0K
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
3.3K
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
3.3K
α-Alkylation of Ketones via Enolate Ions
3.1K
Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the...
3.1K


