合成和结构的新型pyrimidine-thioethers:结构影响的反应性,以及一个不可预测的二甲基化反应反应
Inês C C Costa1,2, Luís M T Frija3, André F Augusto1,2
1Center of Marine Sciences, CCMAR, Gambelas Campus, University of Algarve, 8005-139, Faro, Portugal.
概括
研究人员合成了新型阿米诺皮里米丁-阿里硫化联体,以抑制番氨酸减少酶,这是番胺酸中的关键酶. 反应条件,包括Boc保护,影响了区域选择性,产生了用于药物发现应用的不同产品.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药物发现 药物发现 药物发现
背景情况:
- 阿米诺皮里米丁是具有广泛生物相关性的重要异环结构.
- 含有氨基和二氨基胺基基因的化合物具有抗病毒,抗菌,抗寄生虫,抗真菌,抗癌和抗炎性质.
- 阿米诺皮里米丁在设计针对特定目标的候选药物中至关重要.
研究的目的:
- 合成和描述四种新型阿米诺皮里米丁-阿里硫化联体.
- 为了研究松缩酶的抑制,松缩酶是trypanosomatids的氧化还原途径中的一个关键酶.
- 探索布赫瓦尔德-哈特维格反应的区域选择性在合成这些联物.
主要方法:
- 利用布赫瓦尔德 - 哈特维格合成方法来形成并联.
- 修改反应条件,包括反应时间和Boc保护,以控制区域选择性.
- 采用X射线晶体学来确定合成的结合物和前体的结构.
主要成果:
- 成功合成了四种阿米诺皮里米丁-阿里硫化物联合体 (3,4,5和6).
- 证明了 2,6-二皮里米丁-4-胺的反应时间和 Boc 保护会影响区域选择性.
- 观察到取电子的 Boc 组在 C2 位置促进反应,产生二氨基胺联体.
结论:
- 该研究报告了新型阿米诺皮里米丁-二硫酸联体的合成和结构阐明.
- 布赫瓦尔德-哈特维格反应中的区域选择性可以通过反应参数进行控制.
- 这些发现有助于开发新的治疗药物,以向试类虫病.
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
Preparation of 1° Amines: Gabriel Synthesis
3.8K
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...
3.8K
Preparation of 1° Amines: Azide Synthesis
4.1K
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...
4.1K
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
3.3K
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
3.3K
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
Nucleophilic Aromatic Substitution: Elimination–Addition
4.1K
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...
4.1K


