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.

Synthesis and biological evaluation of a novel 99mTc‐cyclopentadienyltricarbonyl technetium complex as a new potential brain perfusion imaging agent

“…[21] In our hands, no difference in yield was observed using DMAP instead of Hünig's base in the second step. As expected, compound 2 exhibits a typical strong ν C O band (amide I band) at 1643 cm −1 in IR and characteristic ferrocenyl moiety peaks in 13 C NMR (68-77 ppm).…”

“…[23] In order to characterize the technetium-99m complex, we prepared first the corresponding rhenium analog (Scheme 3). Depending of both the nature of the ferrocene derivatives and the oxidation state of the metallic precursor, different synthetic strategies (via double-ligand transfer [13,24,25] or single-ligand transfer reactions [18,25 -27] ) were described for the preparation of 'CpM(CO) 3 '-type complexes (M = 99m Tc or Re) from ferrocene derivatives. Jaouen's team reported recently the preparation of complex Re-2 in 43% yield via a single-ligand transfer using the water-soluble cation Re(CO) 6 + as Re I (CO) 3 source.…”

Cyclopentadienyl technetium (99mTc) tricarbonyl piperidine conjugates: biodistribution and imaging studies

“…Katzenellenbogen and his group have also demonstrated the use of cytectrene complexes as BFCAs. [28][29][30] In the present studies, we have attempted to synthesize cyclopentadienyl technetium tricarbonyl conjugates of two piperidine analogs which were reported by Wenzel et al and used them for biodistribution studies in rats as well as for imaging studies in rabbits. The ferrocene-based precursor ligands, I and II, used in these studies and the proposed structure of the corresponding Tc complexes formed 25,27 are shown in Figure 1.…”

Novel Chemical Strategies for Labeling Small Molecule Ligands for Androgen, Progestin, and Peroxisome Proliferator-Activated Receptors for Imaging Prostate and Breast Cancer and the Heart

“…The first was an integrated complex in which the dimethyl gallium unit substituted for an isopropyl group (20), and in the second, a dimethylgallium salicylaldimine system was a pendant substituent on a non-steroidal estrogen (22). However, we found that neither system was sufficiently stable in water.…”