アミドをα-ケトアミドとα-ヒドロキシアミドに柔軟かつ化学選択的に酸化する
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PubMedで要約を見る
まとめ
この要約は機械生成です。新しい方法により,アミドを過渡金属なしで有価なα-ケトおよびα-ヒドロキシアミドに酸化することができる. これらの反応は,薬剤合成に有用な,高収量,ステレオ選択性,および機能群耐性を提供します.
科学分野
- 有機化学
- 合成方法論
- 薬剤化学
背景
- アミドは有機合成における多用途な機能群である.
- 生物学的活性分子合成には,α-ケトとα-ヒドロキシアミドへのアクセスが不可欠です.
- 既存の酸化方法はしばしば移行金属を必要とし,その範囲と持続可能性を制限しています.
研究 の 目的
- アミド酸化のための新しい移行金属のない方法を開発する.
- α-ケトアミドとα-ヒドロキシアミドを効率的に合成する.
- 複雑な分子合成におけるこれらの方法の広範な適用性を実証する.
主な方法
- すぐ利用可能な試薬を用いた化学選択酸化反応の開発.
- 高収量とステレオ選択性のための反応条件の最適化.
- 生物学的活性化合物の重要な中間物質を合成するために開発された方法の適用.
主要な成果
- 柔軟で化学選択的な酸化方法のセットが確立されました.
- アミドは,α-ケトアミドとα-ヒドロキシアミドに良好から優れた収量で変換された.
- 高機能群耐性およびステレオ選択性が得られた.
- この方法は,ヒストンデセチラーゼ阻害剤の正式な合成に成功しました.
結論
- 開発された過渡金属のない酸化方法は,価値あるアミド誘導体への効率的なアクセスを提供します.
- これらの方法は既存の合成経路に 持続可能で多岐にわたる代替手段を提供します
- 薬の発見と開発におけるこれらの方法の可能性を強調しています.
関連する概念動画
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,...
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...
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
Aldehydes and ketones are prepared from alcohols, alkenes, and alkynes via different reaction pathways. Alcohols are the most commonly used substrates for synthesizing aldehydes and ketones. The conversion of alcohol to aldehyde, which involves the oxidation process, depends on the class of the alcohol used and the strength of the oxidizing agent. For instance, primary alcohol will form an aldehyde when treated with a weak oxidizing agent; however, it gets over-oxidized to a carboxylic acid in...
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...
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
In the Curtius rearrangement, acyl azides are converted into primary amines under thermal conditions, accompanied by the loss of gaseous N2 and CO2. The loss of nitrogen acts as...