通过选择性亚齐里丁胺环开放反应快速sp3丰富的支架生成
Masahito Abe1, Jeremy S Coleman1, Christopher C Presley1
1Warren Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University, Franklin, Tennessee 37067, United States.
The Journal of organic chemistry
|February 10, 2024
概括
循环亚齐里丁胺胺的新型环开反应有效地产生了sp3丰富的支架. 这种方法为药物发现提供了快速访问具有改善物理化学性质的有价值的基结构.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
背景情况:
- 富含sp3混合碳原子的小分子对于药物开发至关重要.
- 设计具有增加sp3特性的分子是药物化学中持续存在的挑战.
研究的目的:
- 开发一种新的合成方法来产生与sp3丰富的脚手架.
- 探索循环-亚齐里丁胺胺环开放反应的实用性,用于创建复杂的分子架构.
主要方法:
- 采用了一种较少探索的循环-亚齐里丁胺胺环开放反应.
- 研究了与各种固态阻碍和功能化亚齐里丁胺胺的反应范围.
- 为拥挤的三级以太形成实现了区域选择性转换.
主要成果:
- 开发了一种方法来快速访问具有高fsp3值的sp3丰富的支架.
- 演示了广泛的反应范围,包括硬质阻碍基质和多种功能组.
- 成功合成了拥挤的三级乙醇,在药物发现中具有潜在的应用.
结论:
- 开发的方法提供了高效的访问sp3丰富的支架与改进的物理化学特性.
- 这种方法适用于药物发现目标,复杂的小分子合成和天然产品合成.
相关概念视频
Preparation of 1° Amines: Azide Synthesis
3.9K
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...
3.9K
Base-Catalyzed Ring-Opening of Epoxides
8.5K
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
8.5K
Acid-Catalyzed Ring-Opening of Epoxides
7.3K
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...
7.3K
Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)
2.6K
Ring-opening metathesis polymerization or ROMP involves strained cycloalkenes as starting materials. The mechanism of ROMP proceeds by reacting cycloalkene with Grubbs catalyst to give metallacyclobutane intermediate which undergoes a ring-opening reaction to form new carbene. The new carbene reacts with another molecule of cycloalkene. Repetition of these steps leads to the formation of an unsaturated open-chain polymer product. All these steps are reversible, however, relieving the ring...
2.6K
Preparation of 1° Amines: Gabriel Synthesis
3.6K
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...
3.6K
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
1.9K
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
1.9K


![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)