测序Ir/Cu介导方法用于 (异质) 场的Meta-选择性C-H放射性化
Jay S Wright1, Liam S Sharninghausen2, Sean Preshlock1
1Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Journal of the American Chemical Society
|April 29, 2021
概括
这项研究提出了一种新的基准方法,用于使用顺序的/铜催化剂对的元选择性C-H放射性化. 该过程有效地产生-18标记的体,而不会隔离中间体,简化放射性体的合成.
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.
- 催化剂是一种催化剂.
背景情况:
- 开发用于将-18 (F) 引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.
- 目前的放射性化技术往往需要专门的设备和多步骤的程序,限制了可访问性.
- 超选择性C-H功能化提供了直接通往特定异构体的途径,但通过放射性化实现这一目标仍然具有挑战性.
研究的目的:
- 开发一种新的,与基板兼容的连续性/铜介导工艺,用于 (异质) 的元选择性C-H放射性化.
- 为了实现高产量和纯度的-18标记 (异质) ,使用简化,单程序.
- 为了证明这种过程的自动化,合成PET成像剂.
主要方法:
- 序列的Ir-催化C ((sp2) -H玻里化 (异质) 基质以形成有机酸.
- 使用[18F]四甲基化物对中间有机酸盐进行直接铜介导的放射化.
- 没有Schlenk或手套箱技术的板执行,避免中间隔离.
主要成果:
- 成功地进行了对1,3-二甲氧化和甲型氨酸衍生物的C-H选择性放射性化.
- [18F]1--3,5-二甲基烯以37 ± 5%的分离放射性化学产量和> 99%的放射性化学纯度获得.
- 标有F的甲氨酸衍生物达到25%的分离放射化学产量,99%的放射化学纯度和0.52Ci/μmol的摩尔活性.
- 该过程在TracerLab FXFN模块上进行自动化.
结论:
- 开发的顺序Ir/Cu介导工艺为元选择性C-H放射性化提供了一种高效且易于使用的方法.
- 该反应的基板,单性质简化了F标记化合物的合成.
- 这种方法对用于PET成像的新型放射追踪剂的常规合成具有前景.
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