Glucosamine Conjugates of Tricarbonylcyclopentadienyl Rhenium(I) and Technetium(I) Cores

To obtain a 99mTc glucose conjugate for imaging, double-ligand transfer (DLT) and related reactions were examined
for the preparation of CpM(CO)3 (Cp = cyclopentadienyl; M = Re, Tc) complexes with pendant carbohydrates at
Cp. Tricarbonyl{N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-d-glucopyranose)cyclopentadienyl carboxamide}rhenium(I) (1a) and tricarbonyl{N-(2-amino-2-deoxy-β-d-glucopyranose)cyclopentadienyl carboxamide}rhenium(I) (2a) were
prepared. The compounds were fully characterized by mass spectrometry, elemental analysis, IR, and NMR
spectroscopy. Full assignment of the NMR spectra verified the pendant nature of the glucosamine moieties in the
solution state and that 2a exists as both anomers. The solid-state structure of 2a was determined by X-ray
crystallography, again confirming the pendant nature of the glucosamine, but differing from the solution state in
that the β anomer crystallized preferentially (93%). Compound 2a was determined to be a high-affinity competitive
inhibitor (Ki = 330 ± 70 μM) of the glucose metabolism enzyme hexokinase, demonstrating that it retains certain
biological activity. The 99mTc analogues 1b and 2b were prepared in moderate radiochemical yields by means of
the single-ligand transfer (SLT) route, which is more pertinent to radiopharmaceutical synthesis.