ルテニウム触媒による生物活性アミンの選択的α,β-デュテレーション
Lorenz Neubert1, Dirk Michalik, Sebastian Bähn
1Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Strasse 29a, D-18059 Rostock, Germany.
Journal of the American Chemical Society
|June 19, 2012
まとめ
この研究は,借用水素を用いた三次アミンの水素-デウテリウム交換のための新しい方法を導入しています. Shvo触媒は,複雑な分子の効率的なデュテレーションを可能にし,生命科学分析のための重要な内部標準を作成します.
科学分野:
- 有機化学 オーガニック・ケミストリー
- カタリシス カタリシス カタリシス
- 薬用化学 薬用化学について
背景:
- 三次アミンは医薬品において極めて重要です.
- 減塩化合物は,LC-MS/MS分析における内部標準として機能する.
- 複雑な分子には,効率的で選択的なデュテレーション方法が必要です.
研究 の 目的:
- 三次アミンの触媒的水素-デウテリウム交換のための新しいプロトコルを開発する.
- 効率的なデュテレーションのために,借用水素の方法論を利用する.
- LC-MS/MS.の内部標準として使用するための減塩化合物を生成する.
主な方法:
- シュボの触媒を用いた触媒的水素-デウテリウム交換.
- 借用水素の方法論を使用しています.
- 生物学的活性のある三次アミンと,薬学的に重要な基質のデュテレーション.
主要な成果:
- 窒素原子に比べてα-およびβ-陽子に対する優れた化学選択性を達成した.
- 高いデウテリウム含有量と幅広い機能群耐性を実証している.
- 市場に出されている薬物化合物を含む,複雑で薬学的に興味深い基質をデュテレーションに成功しました.
結論:
- 開発されたプロトコルは,三次アミンをデュテレーションするための便利で効率的な方法を提供します.
- このアプローチは,生命科学におけるLC-MS/MS分析のための内部標準の合成に役立ちます.
- この方法は,複雑な薬物分子に適用できる高い選択性と機能群耐性を示しています.
関連する概念動画
Preparation 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.
Preparation 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...
Preparation of 1° Amines: Gabriel Synthesis
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
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.
Preparation of Amines: Alkylation of Ammonia and Amines
Alkylation is one of the methods used to prepare amines. Direct alkylation of ammonia or a primary amine with an alkyl halide gives polyalkylated amines along with a quaternary ammonium salt through successive SN2 reactions. This process of making the quaternary salt through the direct alkylation method is called exhaustive alkylation.
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
Amines 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...


