一个简单的立体控制合成盐酸胺A的合成
Leleti Rajender Reddy1, P Saravanan, E J Corey
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Journal of the American Chemical Society
|May 20, 2004
概括
开发了一种新的盐酸胺A合成方法,为研究提供了大量的量. 这一突破使其强大的抗癌特性对各种瘤细胞系进行进一步研究.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 癌症生物学 癌症生物学
背景情况:
- 沙利诺胺A在体外对许多瘤细胞系表现出强烈的细胞毒性活性.
- 该化合物的显著抗癌潜力需要一种可靠和可扩展的合成方法.
- 之前的合成路线没有针对实质性产量或简单性进行优化.
研究的目的:
- 开发一种简单而有效的立体控制合成盐酸胺A.
- 为了进一步进行生物评估,大量生产盐酸胺A.
- 促进对盐酸胺A.抗癌机制的研究.
主要方法:
- 一个新的立体控制合成路径被设计和执行.
- 优化反应条件以提高效率和产量.
- 合成的盐酸胺A的净化和表征.
主要成果:
- 一个简单的,立体选择性的合成salinosporamide A已成功建立.
- 开发的方法产生了大量的盐酸胺A.
- 合成的化合物对各种癌症细胞系保持强烈的细胞毒性活性 (IC(50) ≤10nM).
结论:
- 沙利诺胺A的首次成功合成为获得大量化合物的可行途径提供了可行的途径.
- 这种可扩展的合成将加速研究盐酸胺A在瘤学中的治疗潜力的生物学研究.
- 通过这种方法可获得盐胺A,为药物开发和癌症研究开辟了新的途径.
相关概念视频
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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:
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Brønsted-Lowry Acids and Bases
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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...
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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...


