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Updated: Jul 16, 2026

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Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
サリノスポラミドAの全合成
Atsushi Endo1, Samuel J Danishefsky
1Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021, USA.
Journal of the American Chemical Society
|June 9, 2005
まとめ
強力なプロテアソーム阻害剤であるサリノスポラミドAの全合成は,基板制御反応を用いて達成されました. 主なステップは,分子内アシレーションとセレノサイクリングによる四次炭素の構築を含んでいた.
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
- 合成化学 合成化学とは
背景:
- サリノスポラミドAは,複雑な分子構造を持つ強力なプロテアソーム阻害剤です.
- 複雑な天然製品のための効率的な合成経路の開発は,薬物の発見に不可欠です.
研究 の 目的:
- サリノスポラミドAの全合成を達成するために.
- 複雑な構造モチーフを構築するための新しい合成戦略を探求する.
主な方法:
- (R) -ピログルタミン酸をキラル起始材料として使用した.
- 立体化学的制御のために,基板制御反応を使用した.
- 二つの重要な分子内反応を開発した:炭酸中介の内部アシレーションとセレノサイクル化.
主要な成果:
- サリノスポラミドA (1) を成功して合成した.
- 分子内の連続した四次炭素を効率的に構成する.
- 複雑な合成のための開発された分子内反応の有用性を実証した.
結論:
- サリノスポラミドAの全合成が成功しました.
- 合成戦略は,四次炭素を構成するための効率的な方法を強調しています.
- この研究は,サリノスポラミドAおよび関連アナログにアクセスするための貴重な経路を提供します.
関連する概念動画
Ions as Acids and Bases
Salts with Acidic Ions
Salts are ionic compounds composed of cations and anions, either of which may be capable of undergoing an acid or base ionization reaction with water. Aqueous salt solutions, therefore, may be acidic, basic, or neutral, depending on the relative acid-base strengths of the salt’s constituent ions. For example, dissolving the ammonium chloride in water results in its dissociation, as described by the equation:
Salts are ionic compounds composed of cations and anions, either of which may be capable of undergoing an acid or base ionization reaction with water. Aqueous salt solutions, therefore, may be acidic, basic, or neutral, depending on the relative acid-base strengths of the salt’s constituent ions. For example, dissolving the ammonium chloride in water results in its dissociation, as described by the equation:
Determining the pH of Salt Solutions
The pH of a salt solution is determined by its component anions and cations. Salts that contain pH-neutral anions and the hydronium ion-producing cations form a solution with a pH less than 7. For example, in ammonium nitrate (NH4NO3) solution, NO3− ions do not react with water whereas NH4+ ions produce the hydronium ions resulting in the acidic solution. In contrast, salts that contain pH-neutral cations and the hydroxide ion-producing anions form a solution with a pH greater than 7. For...
Acid 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...
Preparation 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...
Structure of Amines
The hybridized nitrogen atom in amines possesses a lone pair of electrons and is bound to three substituents with a bond angle of around 108°, which is less than the tetrahedral angle of 109.5°. However, the C–N–H bond angle is slightly larger at 112°, with a carbon–nitrogen bond length of 147 pm. This carbon–nitrogen bond length of of amines is longer than the carbon–oxygen bond of alcohols (143 pm) but shorter than alkanes’ carbon–carbon bond (154 pm). These aspects are illustrated in Figure...
Peptidoglycan Synthesis
Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan biosynthesis begins in...

