晚期基C-H化与[18F]化物用于PET成像
Xiongyi Huang1, Wei Liu, Hong Ren
1Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
Journal of the American Chemical Society
|April 29, 2014
概括
这项研究引入了一种新的方法,用于使用催化剂对C-H键进行后期-18标记. 这简化了放射性药物合成,使各种药物分子的快速标记成为可能.
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:
- 晚期放射性标记对于开发诊断和治疗剂至关重要.
- 有效地将-18 ([(18) F]) 纳入复杂分子仍然是一个挑战.
- 目前的方法往往需要前体预激活和繁的净化步骤.
研究的目的:
- 开发一种新的,晚期[(18) F]化方法,用于形C-H键.
- 为了简化[(18) F]标记的放射追踪剂的合成.
- 为了允许在C-H功能化中直接使用没有添加载体的[18) F]化物.
主要方法:
- 使用一个Mn{(salen) OTs催化剂进行直接的[{18) F]化物转移.
- 开发了一种方法,通过催化剂从离子交换子中直接化[(18) F]化物.
- 将该方法应用于各种生物活性分子和药物支架的后期C-H标签.
主要成果:
- 在不到10分钟的时间内,实现了20-72%的放射化学收益率 (RCY) 的形C-H键的[18]F]标记.
- 证明了催化剂能够以>90%的效率化[F18) ]化物,而无需干燥阶段.
- 在没有前体预激活的情况下,成功标记了八种药物分子,包括COX,ACE,MAO和PDE抑制剂.
结论:
- 开发的Mn催化方法代表了阿里法性C-H键的第一个后期[{18) F]化.
- 这种方法大大简化了放射性药物合成协议,并缩短了合成时间.
- 该方法有望加速开发新的[(18) F]标记成像剂和治疗药物.
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