重温比吉内利式反应:溶剂效应,机制,生物应用以及对几篇文献报告的纠正
Pedro S Beck1, Arthur G Leitão1, Yasmin B Santana1
1University of Brasilia, Institute of Chemistry, Laboratory of Medicinal and Technological Chemistry. Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. brenno.ipi@gmail.com.
Organic & biomolecular chemistry
|April 23, 2024
概括
这项研究发现了比吉内利式反应中的结构错误,揭示了伪衍生品而不是预期的产品. 严格的分析纠正了分配,并揭示了伪添加物的新细胞机制,影响了合成化学的重新评估.
科学领域:
- 有机合成 有机合成
- 药用化学 医学化学
- 化学晶体学 化学晶体学
背景情况:
- 比吉内利类反应是合成二皮里米丁的关键多元组分反应 (MCR).
- 之前的研究报告了各种MCR引证,但它们的结构完整性和反应机制需要进行批判性评估.
- 溶剂的影响对反应结果和产品稳定性起着重要作用.
研究的目的:
- 通过使用溶剂效应模型,批判性地重新评估报告的比尼内利类反应.
- 为了识别和纠正MCR产品中的结构性错误分配.
- 研究新发现的伪添加物的生物活动和细胞机制.
主要方法:
- 应用Kamlet-Abboud-Taft (KAT) 溶剂效应模型.
- 复制文献综合条件和详细表征.
- 光谱技术 (NMR,ESI-MS/MS),元素分析,点和单晶X射线衍射.
- 生物测定,对接研究和RMSD分析.
主要成果:
- 发现结构性错误分配,识别伪三元衍生品,而不是预期的MCR引证.
- 无法复制某些文献条件,表明报告的MCR和机制中的潜在不准确性.
- 阐明一个完整的催化循环,并提出纠正的结构.
- 鉴定了一种伪添加剂的新型细胞作用机制,作为类似于Monastrol的Eg5抑制剂.
结论:
- 在众多比吉内利式反应报告中,需要对结构性赋值进行批判性重新检查和纠正.
- 在合成化学中强调严格的表征和验证,以确保报告的化合物和活动的准确性.
- 伪添加物可能表现出独特的生物特性,需要进一步研究.
更多相关视频
06:31Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators
Published on: November 27, 2015
9.6K
13:05Reliable Mechanochemistry: Protocols for Reproducible Outcomes of Neat and Liquid Assisted Ball-mill Grinding Experiments
Published on: January 23, 2018
10.6K
相关概念视频
01:17Pericyclic Reactions: Introduction
8.3K
Pericyclic reactions are organic reactions that occur via a concerted mechanism without generating any intermediates. The reactions proceed through the movement of electrons in a closed loop to form a cyclic transition state, where rearrangement of the σ and π bonds yields specific products.
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic...
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic...
8.3K
02:25SN1 Reaction: Mechanism
11.8K
Kinetic studies of ionization of a tertiary halide in a protic solvent suggest that only the substrate participates in the rate-determining step (slow step). The nucleophile is involved only after the slowest step. The SN1 reaction takes place in a multiple-step mechanism.
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
11.8K
02:46E1 Reaction: Kinetics and Mechanism
15.4K
Here, in contrast to the E2 reaction mechanism, we delve into the aspects of the E1 reaction mechanism, which has two steps: rate-limiting loss of the leaving group and abstraction of the beta hydrogen by a weak base. Typically, the experimental proof for the E1 mechanism is via kinetic studies or isotope studies. While the former demonstrates the first-order kinetics—the dependence of the reaction solely on substrate concentration—the latter proves the abstraction of hydrogen only...
15.4K
02:27SN2 Reaction: Mechanism
14.3K
The kinetic studies of SN2 reactions suggest an essential feature of its mechanism: it is a single-step process without intermediates. Here, both the nucleophile and the substrate participate in the rate-determining step.
The presence of the more electronegative halogen in the substrate creates a polarized carbon-halide bond. The halide pulls the electron cloud generating an electrophilic center at the carbon atom. Thus, the carbon atom carries a partial positive charge while the halide has a...
The presence of the more electronegative halogen in the substrate creates a polarized carbon-halide bond. The halide pulls the electron cloud generating an electrophilic center at the carbon atom. Thus, the carbon atom carries a partial positive charge while the halide has a...
14.3K
02:34Nucleophilic Substitution Reactions
16.4K
Historical perspective
In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion suggested the involvement of optical inversion during the substitution reaction. Further, in 1930, Sir Christopher Ingold described for the first time two different forms of nucleophilic substitution reactions, which are known as SN1 (nucleophilic substitution unimolecular) and SN2 (nucleophilic substitution...
In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion suggested the involvement of optical inversion during the substitution reaction. Further, in 1930, Sir Christopher Ingold described for the first time two different forms of nucleophilic substitution reactions, which are known as SN1 (nucleophilic substitution unimolecular) and SN2 (nucleophilic substitution...
16.4K
02:45E2 Reaction: Kinetics and Mechanism
10.2K
SN2 substitutions and E2 eliminations of alkyl halides proceed via a concerted pathway. While the nucleophile attacks the alpha carbon in SN2 reactions, it functions as a strong base and abstracts a beta hydrogen in the E2 mechanism. The rate-limiting transition state in E2 elimination reactions is characterized by partially broken carbon–hydrogen and carbon–halogen bonds and a partially formed pi bond between the alpha and beta carbons. The beta hydrogen and halide are eliminated...
10.2K