Jobson Nicola K, Spike Rosemary, Crawford Andrew R, Dewar Deborah, Pimlott Sally L, Sutherland Andrew
WestChem, Department of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow, UK G12 8QQ.
Org Biomol Chem. 2008 Jul 7;6(13):2369-76. doi: 10.1039/b802819b. Epub 2008 Apr 30.
With the aim of developing a new SPECT imaging agent for the noradrenaline transporter, a twelve-step stereoselective synthesis of iodinated analogues of (2S,3R)- and (2R,3S)-reboxetine has been achieved from 4-bromobenzaldehyde. The key steps involve a Sharpless asymmetric epoxidation to establish the stereogenic centres and a copper catalysed aromatic halogen exchange reaction to introduce the key iodine atom. In vitro testing of these compounds using a [(3)H]nisoxetine displacement assay with homogenised rat brain shows both compounds to have significant affinity, with K(i) values of 320.8 nM and 58.2 nM for (2S,3R)- and (2R,3S)-iodoreboxetine respectively.
为了开发一种用于去甲肾上腺素转运体的新型单光子发射计算机断层扫描（SPECT）成像剂，已从4-溴苯甲醛出发，通过十二步立体选择性合成法制备了（2S,3R）-和（2R,3S）-瑞波西汀的碘化类似物。关键步骤包括利用夏普莱斯不对称环氧化反应来构建手性中心，以及通过铜催化的芳基卤交换反应引入关键碘原子。使用匀浆大鼠脑的[³H]尼索西汀置换试验对这些化合物进行体外测试，结果表明这两种化合物都具有显著亲和力，（2S,3R）-碘瑞波西汀和（2R,3S）-碘瑞波西汀的抑制常数（Kᵢ）值分别为320.8 nM和58.2 nM。
