不受保护的-18标记的α-三级胺基的介导放射合成
Jay S Wright1, Richard Ma1, E William Webb1
1Department of Radiology, University of Michigan, Ann Arbor, MI-48109, USA.
Angewandte Chemie (International ed. in English)
|November 27, 2023
概括
本研究介绍了一种使用三酸盐和四甲基化制造-18标记胺的新方法. 该过程对于无菌阻碍的场所是高效的,并且已经自动化用于放射性同位素的生产.
科学领域:
- 放射化学 放射化学是指辐射化学.
- 有机合成 有机合成
- 药用化学 医学化学
背景情况:
- 开发用于将-18纳入有机分子的高效方法对于正电子发射断层扫描 (PET) 成像至关重要.
- 在放射性化反应中,绝缘阻碍的三级站点构成了重大挑战.
研究的目的:
- 开发一种新的三甲酸介导方法,用于合成标记为α-三级胺的-18 .
- 为了优化反应条件的高放射性化学产量和纯度,特别是在受阻的三级位置.
主要方法:
- 使用三酸盐 (Zn(OTf) 2) 作为α-三级胺的放射性化媒介.
- 使用没有载体添加的[18F]四甲化物作为化物来源.
- 包含1,5,7-triazabicyclo[4.4.0]dec-5-ene作为增强放射化学转换的关键添加剂.
主要成果:
- 实现了高的放射化学转化和产量,用于合成标记为-18的α-三级胺,即使在无菌阻碍的三级站点.
- 成功自动化了放射性化过程,使得可以生产超过200mCi (>7.4 GBq) 的模型放射性化物.
- 机械研究揭示了一种使用N-硫烯胺基底的新型核性C-H放射性化途径.
结论:
- 开发的Zn(OTf) 2介导方法为[18F]α-三级胺提供了一条高效且稳健的途径.
- 这个过程的自动化有助于常规生产有价值的PET成像剂.
- 发现一种新的C-H放射性化机制扩大了放射性药物开发的工具包.
相关概念视频
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
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
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
3.2K
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.
3.2K
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
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
6.1K
Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.
6.1K

![Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F55537.jpg&w=3840&q=50)
![Radiosynthesis of 1-2-[18F]Fluoroethyl-L-Tryptophan using a One-pot, Two-step Protocol](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F63025.jpg&w=3840&q=50)