用同位素标记CO2的阿尔代催化剂制备C1标记的α-氨基酸的实用指南
Michael G J Doyle1, Braeden A Mair2,3, Anna Sib4
1Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
Nature protocols
|March 29, 2024
概括
这项研究引入了一种新的,具有成本效益的方法,用于制备以同位素碳标记的α-氨基酸,使用二氧化碳 (CO2) 的后期标记. 这一突破简化了用于药理学和医学成像的有价值化合物的合成.
科学领域:
- 有机化学 有机化学
- 放射化学 放射化学是指辐射化学.
- 合成化学 合成化学
背景情况:
- 同位素碳标记的α-氨基酸对于药理学和医学成像学至关重要.
- 目前合成这些化合物的方法涉及早期的同位素标签,导致高成本和漫长的程序.
- 需要更高效和更容易获得的合成策略.
研究的目的:
- 为C1标记的α-氨基酸开发一种新的后期标签协议.
- 使用随时可用的化物催化剂和二氧化碳 (CO2) 同位素 (*C = 14,13,11).
- 为了建立一个单碳酸盐交换反应,对未受保护的α-氨基酸.
主要方法:
- 在基本条件下在二甲基硫氧化物 (DMSO) 中使用未受保护的α-氨基酸和[*C]CO2的碳酸盐交换反应.
- 在50-90°C的温度下加热反应组件.
- 为合成 (±) -[1-13C]氨酸, (±) -[1-11C]氨酸和 (±) -[1-14C]氨酸而开发的特殊程序.
主要成果:
- 使用后期标记方法成功合成C1标记的氨同位素.
- 对于 (±) - [1-13C]氨酸,与70-88%的同位素合并实现了60-80%的分离产量.
- 在1小时内 (±) -[1-11C]氨酸 (13%放射性化学产量) 和2天内 (±) -[1-14C]氨酸 (11%放射性化学产量) 的快速合成.
结论:
- 开发的协议在合成C1标记的α-氨基酸方面取得了突破,包括非天然衍生物.
- 与现有方法相比,这种后期标签策略显著降低了合成成本和制备时间.
- 该方法可扩展 (高达0.5mmol) 并广泛适用于各种α-氨基酸.
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