新型曼尼希型多元件反应:发现,机制和应用
Xianjing Zhou1, Zhencheng Lai1, Jiaming Li1
1Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Accounts of chemical research
|July 1, 2025
概括
这项研究引入了用于合成复杂分子的新型多元组分反应 (MCR),特别是在药物发现和天然产品修改中实现未激活的C-H键的曼尼赫反应.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成方法论 合成方法论
背景情况:
- 多元组分反应 (MCR) 对于高效合成复杂分子至关重要.
- 曼尼赫反应是一个关键的MCR,通常涉及激活的C-H键.
- 对于未被激活的C-H键,特别是C(sp3)-H,开发曼尼赫反应是具有挑战性的.
研究的目的:
- 开发新的曼尼赫型多元组分反应,涉及未激活的C-H键.
- 探索这些MCR在自然产品和药物发现的支架进化中的应用.
- 阐明新型曼尼赫反应的机械路径.
主要方法:
- 调查了一项偶然的发现,导致双曼尼赫基化.
- 进行了涉及多个曼尼赫,逆曼尼赫和脱步骤的机制研究.
- 开发了Mannich类型的MCR,使用佐/英多,甲和基胺化物.
主要成果:
- 在C ((sp2) -H和未激活的基C ((sp3) -H键中实现了前所未有的基化.
- 成功合成了与皮佩里丁合的佐/醇和醇合的七个成员异环.
- 与医学上相关的功能和tanshinones成功的支架进化证明了广泛的兼容性.
结论:
- 开发了一种强大的合成工具箱,用于天然产品和药物发现的支架进化.
- 开创了tanshinones的化学进化,导致强大的NLRP3炎症酶抑制剂和有效的ALI治疗.
- 产生了有前途的候选药物,包括新的HDAC,P-gp和STAT3抑制剂,突出了MCRs的治疗潜力.
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
9.7K
10:51The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes
Published on: April 10, 2015
12.3K
相关概念视频
02:34Nucleophilic Substitution Reactions
17.1K
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...
17.1K
03:06Reaction Mechanisms
26.5K
Chemical reactions often occur in a stepwise fashion, involving two or more distinct reactions taking place in a sequence. A balanced equation indicates the reacting species and the product species, but it reveals no details about how the reaction occurs at the molecular level. The reaction mechanism (or reaction path) provides details regarding the precise, step-by-step process by which a reaction occurs.
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
26.5K
02:31Multi-Step Reactions
7.5K
Chemical reactions often occur in a stepwise fashion involving two or more distinct reactions taking place in a sequence. A balanced equation indicates the reacting species and the product species, but it reveals no details about how the reaction occurs at the molecular level. The reaction mechanism (or reaction path) provides details regarding the precise, step-by-step process by which a reaction occurs. Each of the steps in a reaction mechanism is called an elementary reaction. These...
7.5K
01:26Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
3.6K
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
3.6K
01:11Radical Reactivity: Overview
2.2K
Radicals, the highly reactive species, gain stability by undergoing three different reactions. The first reaction involves a radical-radical coupling, in which a radical combines with another radical, forming a spin‐paired molecule. The second reaction is between a radical and a spin‐paired molecule, generating a new radical and a new spin‐paired molecule. The third reaction is radical decomposition in a unimolecular reaction, forming a new radical and a spin‐paired...
2.2K
01:17Radical Anti-Markovnikov Addition to Alkenes: Mechanism
4.1K
The reaction of hydrogen bromide with alkenes in the presence of hydroperoxides or peroxides proceeds via anti-Markovnikov addition. The radical chain reaction comprises initiation, propagation, and termination steps.
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
4.1K