結合還元と還元性アミネーションのための多機能生物触媒
Thomas W Thorpe1, James R Marshall1, Vanessa Harawa1
1Department of Chemistry, University of Manchester, Manchester Institute of Biotechnology, Manchester, UK.
Nature
|April 7, 2022
まとめ
新種の酵素であるEneIREDは 薬剤や農薬に不可欠なキラルアミンダイアステロエーマーを 効率的に合成します この生物触媒は,非対称合成のための報告されていないメカニズムを使用して,生産を簡素化します.
科学分野:
- 生物触媒と合成生物学
- 有機化学
背景:
- チラルアミン二ステロエーマーは,医薬品と農薬に不可欠です.
- 現在の合成方法はしばしば非効率で多段階です.
- エナチオメアの生化学的性質が異なるため,非対称な合成が重要である.
研究 の 目的:
- キラルアミン合成のための新しい多機能生物触媒の特徴づけ
- 酵素の独特の触媒メカニズムを解明する
- 複雑なキラルアミンの非対称合成における酵素の可能性を調査する.
主な方法:
- メタゲノムイミン還元酵素 (IRED) コレクションによる酵素発見.
- 機械的および構造的研究を含む生物触媒の特徴づけ
- 炭基素とアミンの結合のための酵素の基板の範囲を評価する.
主要な成果:
- Pseudomonas の新しい生物触媒である EneIRED の識別と特徴付け
- EneIREDは,アミン活性化結合アルケンの還元と還元性アミネーションを含む未報告のメカニズムを使用しています.
- 酵素は,様々な基板から最大3つのステレオセンターを持つキラルアミンダイアステロエーマーを効率的に生成します.
結論:
- EneIREDは価値あるキラルアミンダイアステロエーマーへの効率的な経路を提供します.
- IREDファミリーは新しい酵素活動を発見するための有望なプラットフォームとして機能します.
- 合成生物学と有機合成の応用が進んでいます
関連する概念動画
01:38Preparation of Amines: Reductive Amination of Aldehydes and Ketones
3.2K
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
3.2K
01:27Phase I Reactions: Reductive Reactions
286
Phase I biotransformation reductive reactions are chemical processes that modify drugs by introducing or revealing polar functional groups via reduction. Enzymes called reductases catalyze these reactions, playing a pivotal role in drug metabolism by transforming lipophilic drugs into more polar, water-soluble metabolites for easy excretion. An essential type of reductive reaction is the carbonyl group reduction, where aldehydes and ketones are reduced to alcohols. An example is the...
286
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
3.5K
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...
3.5K
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
4.1K
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
4.1K
02:23Alcohols from Carbonyl Compounds: Reduction
10.9K
Reduction is a simple strategy to convert a carbonyl group to a hydroxyl group. The three major pathways to reduce carbonyls to alcohols are catalytic hydrogenation, hydride reduction, and borane reduction.
Catalytic hydrogenation is similar to the reduction of an alkene or alkyne by adding H2 across the pi bond in the presence of transition metal catalysts like Raney Ni, Pd–C, Pt, or Ru. Aldehydes and ketones can be reduced by this method, often under mild to moderate heat (25–100°C) and...
Catalytic hydrogenation is similar to the reduction of an alkene or alkyne by adding H2 across the pi bond in the presence of transition metal catalysts like Raney Ni, Pd–C, Pt, or Ru. Aldehydes and ketones can be reduced by this method, often under mild to moderate heat (25–100°C) and...
10.9K
00:55Nitriles to Amines: LiAlH4 Reduction
3.8K
Nitriles are reduced to amines in the presence of strong reducing agents like lithium aluminum hydride through a typical nucleophilic acyl substitution. The reaction requires two equivalents of the reducing agent. The reducing agent acts as a source of hydride ions.
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
3.8K