Stereoselective synthesis of (2S,3R)- and (2R,3S)-iodoreboxetine; potential SPECT imaging agents for the noradrenaline transporter.
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.
WestChem, Department of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow, UK G12 8QQ.
Nicola K
NK
Jobson
Rosemary
R
Spike
Andrew R
AR
Crawford
Deborah
D
Dewar
Sally L
SL
Pimlott
Andrew
A
Sutherland
D007455:Iodine / Q000737:chemistry; D009025:Morpholines / Q000032:analysis* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism*; D011854:Radiochemistry; D000077593:Reboxetine; D013237:Stereoisomerism; D013379:Substrate Specificity; D015899:Tomography, Emission-Computed, Single-Photon
D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C531378:iodoreboxetine; D000077593:Reboxetine; D007455:Iodine