アミドとペプチドの合成におけるアンポルングの反応性
Bo Shen1, Dawn M Makley, Jeffrey N Johnston
1Department of Chemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235-1822, USA.
Nature
|June 26, 2010
まとめ
この研究は,アミド結合を合成するための新しい方法を導入し,アミンとニトロアルカンをヨウ素で活性化します. このアプローチは反応物質の極性を逆転させ,ペプチド合成のための革新的な経路を提供します.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 薬用化学 薬用化学について
- バイオケミストリー バイオケミストリー
背景:
- アミド結合はペプチド,タンパク質,治療薬の基本です.
- 現在のアミド結合形成方法は主に脱水性であり,酸化性および根性的な代替方法があります.
- 伝統的な方法は,電友性炭素と核友性窒素を含む.
研究 の 目的:
- アミド結合構築のための新しい方法を開発する.
- ニトロアルカンをアシルアニオン等価物として使用することを調査する.
- C-Nボンド形成のためのアンポルング戦略を調査する.
主な方法:
- 電子性ヨウ素源を使用したアミンとニトロアルカンの活性化.
- アミド産物の直接的形成.
- 極性逆転 (umpolung) を含む反応機構の分析.
主要な成果:
- アミンとニトロアルカンから直接アミド結合の成功合成.
- 反応物質が典型的な電愛性/核愛性役割を逆転させるアンポリングメカニズムの実証.
- ニトロアルカンは,有効なアシルアニオン等価体として機能する.
結論:
- アミドとペプチドの合成に概念的に革新的なアプローチが確立されています.
- この方法は,伝統的な極性を逆転することによって,C-N結合形成のための新しい経路を提供します.
- この戦略を使用して効率的でエナチオセレクティブなペプチド合成の可能性.
関連する概念動画
01:29Preparation of Amides
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
01:07Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
01:19Amines to Amides: Acylation of Amines
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
01:22Preparation of 1° Amines: Azide Synthesis
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
01:28Amides to Carboxylic Acids: Hydrolysis
Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
01:38Preparation of Amines: Reductive Amination of Aldehydes and Ketones
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.