アリファ酸およびベンゾ酸塩基のパラジウム触媒による炭素同位体交換
Donald R Gauthier1, Nelo R Rivera1, Haifeng Yang1
1Department of Process Research and Development , Merck & Co., Inc. , Rahway , New Jersey 07065 , United States.
Journal of the American Chemical Society
|November 3, 2018
まとめ
パラジウム触媒による新しい方法は,炭素同位体 (炭素-13と炭素-14) をカルボニル化合物と交換することを可能にします. このテクニックは,医薬品や天然製品のような複雑な分子のラベル付けに有用です.
科学分野:
- 有機化学
- 同位体化学
- カタリシス
背景:
- カルボニル化合物は,多用途の合成中間物質である.
- 炭素同位体 (例えば,13C,14C) を含めることは,メカニズム研究,代謝追跡,放射性標識に不可欠である.
- 炭素イソトープ交換の既存の方法は複雑で,範囲は限られている.
研究 の 目的:
- パラジアム触媒による炭素同位体交換のための 操作的に単純なプロトコルを開発する.
- 13COと14COが活性化されたアリファートカルボニルとベンゾイックカルボニルに組み込まれていることを証明する.
- 後期段階の機能化におけるメソッドの有用性と,多様な機能グループとの互換性を示します.
主な方法:
- パラジウム触媒による炭化反応
- 13COと14COガスの使用
- 基質の範囲には活性化アリファティックおよびベンゾ酸カルボニル化合物が含まれます.
- 自然産物の誘導体や医薬品に適用する.
主要な成果:
- 13COと14COの交換のための簡単なプロトコルの開発に成功しました.
- 様々な基板との機能群の互換性が実証されている.
- 13Cと14Cのラベルを貼ったいくつかのビルディングブロック,天然製品の派生物,および医薬品の製造.
- この方法は,後期的な炭素同位体の組み込みを可能にします.
結論:
- 提出されたプロトコルは,炭素同位体を有機分子に導入するための効率的で簡単な経路を提供します.
- この方法は,研究開発,特に後期機能化のためのラベル付き化合物の合成に価値があります.
- 証明された互換性は,医薬品化学と天然製品の合成における炭素同位体ラベルの適用範囲を拡大する.
関連する概念動画
Carboxylic Acids to Acid Chlorides
8.9K
Carboxylic acids react with SOCl2 or PCl5 to form acid chlorides. Amongst the carboxylic acid derivatives, acid chlorides are the most reactive and synthetically important derivatives. They are useful reagents for Friedel–Crafts acylation of some aromatic compounds.
8.9K
Acid-Catalyzed Ring-Opening of Epoxides
9.0K
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...
9.0K
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
727
Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
727
Isotopes
64.5K
Elements have a set number of protons that determines their atomic number (Z). For example, all atoms with eight protons are oxygen; however, the number of neutrons can vary for atoms of the same element. The sum of the number of protons and the number of neutrons is the mass number (A). Atoms with the same atomic number but different mass numbers are called isotopes. Elements can have multiple isotopes, for example, carbon-12, carbon-13, and carbon-14.
An element's atomic mass, or weight,...
An element's atomic mass, or weight,...
64.5K
Acid-Catalyzed Hydration of Alkenes
17.2K
Alkenes react with water in the presence of an acid to form an alcohol. In the absence of acid, hydration of alkenes does not occur at a significant rate, and the acid is not consumed in the reaction. Therefore, alkene hydration is an acid-catalyzed reaction.
17.2K
Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis
4.1K
Hydrolysis of esters under acidic conditions proceeds through a nucleophilic acyl substitution. In the presence of excess water, the reaction proceeds in a reversible manner, forming carboxylic acids and alcohols.
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
4.1K


