Synthesis of cyclopentadienyltricarbonyl rhenium phenyltropanes by double ligand transfer: organometallic ligands for the dopamine transporter.

Abstract

Cyclopentadienyltricarbonyl rhenium (CpRe(CO)(3)) systems can be prepared from ferrocenes and perrhenate by a double ligand transfer (DLT) reaction that gives reasonable yields and shows excellent functional group tolerance. We used this reaction for the direct preparation of CpRe(CO)(3)-phenyltropane conjugates. Such agents, when labeled with technetium-99m, might function as imaging agents for the dopamine transporter (DAT) system that would be useful for assessing the onset and severity of Parkinson's disease. Of the CpRe(CO)(3)-tropane conjugates prepared by the DLT reaction (as well as other analogues prepared by related methods), those substituted at the N-8 position seem most promising; their affinity for the DAT in all cases was high, and their ferrocene precursors for the DLT reaction can be prepared in a convenient manner. By contrast, the 3 beta-conjugates were poor DAT binders. The modular nature of these systems offers considerable flexibility that could be used to improve the binding characteristics of these compounds further.