通过正式的SO2插入C-N键进入硫胺
Myojeong Kim1, Carys E Obertone1, Christopher B Kelly2
1Department of Chemistry, University of Chicago, Chicago, IL, USA.
Nature chemistry
|June 20, 2025
概括
这项研究引入了一种新方法,通过插入二氧化硫 (SO2) 来直接从初级氨基中合成初级硫胺. 这种方法通过使药物库的快速多样化和活性药物成分的修改来简化药物发现.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 化学合成 化学合成
背景情况:
- 功能组的相互转换对于优化和药物化学库的多样化至关重要.
- 由于需要预先激活起始材料,直接合成初级硫胺酸具有挑战性.
研究的目的:
- 从初级氨基酸中开发一种用于直接合成初级硫胺的新方法.
- 为了使有效的图书馆多样化和修改活性药物成分.
主要方法:
- 使用双重功能异构胺试剂将二氧化硫 (SO2) 插入到初级胺的C-N键中.
- 涉及异二基链机制的机制研究.
- 高通量库的多样化和应用在已批准的活性药物成分中.
主要成果:
- 从初级胺基直接合成初级硫胺基,没有预激活.
- 开发的协议容纳了广泛的功能.
- 在高通量图书馆多样化和现有药物的修改中成功应用.
结论:
- 这种新的SO2插入方法提供了一个容易通往初级硫胺的途径,反转的特性.
- 这种方法通过高效的库合成和修改来促进药物发现.
- 该协议使异替代策略成为可能,例如CO-to-SO2替代.
相关概念视频
Preparation and Reactions of Sulfides
5.1K
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
5.1K
Electrophilic Aromatic Substitution: Sulfonation of Benzene
6.5K
Sulfonation of benzene is a reaction wherein benzene is treated with fuming sulfuric acid at room temperature to produce benzenesulfonic acid. Fuming sulfuric acid is a mixture of sulfur trioxide and concentrated sulfuric acid.
6.5K
Amines to Sulfonamides: The Hinsberg Test
3.8K
The Hinsberg test is a method to identify primary, secondary and tertiary amines, named after its pioneer, Oscar Hinsberg. Here, amines are treated with benzenesulfonyl chloride, also known as the Hinsberg reagent, in the presence of an excess of aqueous base, followed by acidification. Based on the nature of the amines, different changes are observed.
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing...
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing...
3.8K
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
455
Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme...
455
Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)
4.1K
Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
4.1K
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
2.2K
Treating arylamines with nitrous acid gives aryldiazonium salts that are effective substrates in nucleophilic aromatic substitution reactions. The diazonio group in these salts can be easily displaced by different nucleophiles, yielding a wide variety of substituted benzenes. The leaving group departs as nitrogen gas, and this easy elimination is the driving force for the substitution reaction.
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...
2.2K


