在DNA上合成多替代的内
András Gy Németh1,2, Levente Kollár1,3,2, Krisztina Németh1,4
1Medicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary.
Organic letters
|December 18, 2023
概括
我们开发了一种与DNA兼容的新方法,用于合成多替代性英多尔,这对于药物发现至关重要. 这种方法可以有效地构建用于识别新疗法化合物的库.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 化学生物学 化学生物学
背景情况:
- 用DNA编码的库技术对于早期药物发现至关重要.
- 需要使用DNA兼容的合成方法来制造各种异环化合物.
- 印度尔是具有显著治疗意义的基质环的关键类别.
研究的目的:
- 报告首次在DNA上合成多重置换的内醇.
- 开发一种DNA兼容的级联反应,用于醇合成.
- 通过使用DNA编码的图书馆技术,使各种化学空间的探索成为可能.
主要方法:
- 在DNA合成中使用级联反应.
- 索诺加希拉合,然后进行分子内环闭合,以形成内醇.
- 在C3位置进行进一步的功能化,Suzuki合器.
主要成果:
- 在DNA上直接成功合成多重替代的醇.
- 一个级反应的演示,该反应结合了Sonogashira合和循环.
- 通过随后的苏苏基合来扩大化学多样性.
- 以高保真度构建一个基于印的模拟DNA编码图书馆.
结论:
- 开发的方法为DNA上道合成提供了强大而高效的途径.
- 这种方法显著提高了DNA编码库在药物发现中的实用性.
- 该方法允许快速探索内置脚手架周围的化学空间.
相关概念视频
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
3.4K
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
3.4K
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
10.2K
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
10.2K
Diels–Alder Reaction: Characteristics of Dienes
4.1K
The Diels–Alder reaction brings together a diene and a dienophile to form a six-membered ring. Both components have unique characteristics that influence the rate of the reaction.
Characteristics of the diene
Conformation
The simplest example of a diene is 1,3-butadiene, an acyclic conjugated π system. At room temperature, the molecule exists as a mixture of s-cis and s-trans conformers by virtue of rotation around the carbon–carbon single bond. Although the s-trans isomer is...
Characteristics of the diene
Conformation
The simplest example of a diene is 1,3-butadiene, an acyclic conjugated π system. At room temperature, the molecule exists as a mixture of s-cis and s-trans conformers by virtue of rotation around the carbon–carbon single bond. Although the s-trans isomer is...
4.1K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
6.1K
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
6.1K
Nucleophilic Aromatic Substitution: Elimination–Addition
4.0K
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...
4.0K
Disubstituted Cyclohexanes: cis-trans Isomerism
12.0K
Depending upon the different spatial orientation of the substituents, the disubstituted cycloalkanes exhibit two types of stereoisomers. The cis isomers have the substituents on the same side of the ring, whereas the trans isomers have the substituents on the opposite sides. These stereoisomers exhibit different physical properties and cannot be interconverted without breaking the carbon-carbon bonds.
In cyclohexane, the substituents can occupy different positions generating distinct isomers....
In cyclohexane, the substituents can occupy different positions generating distinct isomers....
12.0K


