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)

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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 > Institute of Neuroscience and Psychology
College of Science and Engineering > School of Chemistry
Journal Name:Organic and Biomolecular Chemistry
ISSN:1477-0520

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