胺酸提供了一般的 thioamide, amidine 和 imidazolone 键同质醇的接入
Jacob Byerly-Duke1, Emily A O'Brien1, Brendan J Wall1
1Department of Chemistry, Iowa State University, Ames, IA, United States.
Methods in enzymology
|June 17, 2024
概括
这项研究引入了一种新的方法,用于将胺物纳入基骨,使用胺酸保护基. 这一突破使得新结构和异环修饰的合成能够用于先进的设计.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 类化学 类化学
背景情况:
- 像胺,氨基酸和异环等键同位素提供了修改骨的方法.
- 从历史上看,有限的合成方法阻碍了胺在化工中的使用.
- 在安装这些修改时,胺酸保护组为合成挑战提供了解决方案.
研究的目的:
- 开发一种强大且通用的方法,用于将氨基酸引入脊髓.
- 为了探索 (4H) - imidazolone异循环的形成,在树脂胺素作为cis-amide异体.
- 通过提供对新架构和构造的访问来推进体设计.
主要方法:
- 利用胺酸保护基来克服合成中的反应性问题.
- 在树脂上安装阿米丁的一般程序的开发.
- 研究阿米丁的循环形成 (4H) - 伊米达佐异环的过程.
主要成果:
- 建立了一个强大的和通用的合成路径,用于将胺素纳入质主链.
- 在-树脂胺基因被成功转化为 (4H) - imidazolone 异环.
- 这种方法有助于创建几何限制的形状.
结论:
- 开发的基于 thioimidate 的策略为合成具有胺和异环修饰的提供了一个多功能平台.
- 这项工作显著扩大了类工程的工具包,使得探索新设计和功能成为可能.
- 该方法为以前无法访问的质架构提供了一种普遍适用的方法.
相关概念视频
Preparation of Amides
3.0K
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...
3.0K
Preparation of 1° Amines: Azide Synthesis
3.9K
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...
3.9K
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
4.6K
Primary amines react with carbonyl compounds—aldehydes and ketones—to generate imines. Imines consist of a C=N double bond and are named Schiff bases after its discoverer—the German chemist Hugo Schiff. On the other hand, secondary amines react with carbonyl compounds to give enamines. In enamines, the presence of a C=C double bond adjacent to the nitrogen atom leads to the delocalization of the lone pair.
4.6K
Preparation of 1° Amines: Gabriel Synthesis
3.5K
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...
3.5K
Aldehydes and Ketones with Amines: Imine Formation Mechanism
5.4K
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
5.4K
Amines to Amides: Acylation of Amines
2.4K
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...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
2.4K


