Stereoselective synthesis of (2S,3R)- and (2R,3S)-iodoreboxetine; potential SPECT imaging agents for the noradrenaline transporter

Jobson, N., Spike, R., Crawford, A., Dewar, D., Pimlott, S. and Sutherland, A. (2008) Stereoselective synthesis of (2S,3R)- and (2R,3S)-iodoreboxetine; potential SPECT imaging agents for the noradrenaline transporter. Organic and Biomolecular Chemistry, 6(13), pp. 2369-2376. (doi: 10.1039/b802819b)

Abstract

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 [3H]nisoxetine displacement assay with homogenised rat brain shows both compounds to have significant affinity, with Ki values of 320.8 nM and 58.2 nM for (2S,3R)- and (2R,3S)-iodoreboxetine respectively.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dewar, Dr Deborah and Pimlott, Dr Sally and Sutherland, Professor Andrew
• Authors: Jobson, N., Spike, R., Crawford, A., Dewar, D., Pimlott, S., and Sutherland, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Science and Engineering > School of Chemistry
• Journal Name: Organic and Biomolecular Chemistry
• ISSN: 1477-0520