A versatile synthetic route to the preparation of N-15 heterocycles

摘要

A robust medium-scale (approximately 3 g) synthetic method for N-15 labeling of pyridine (N-15-Py) is reported based on the Zincke reaction. N-15 enrichment in excess of 81% was achieved with approximately 33% yield. N-15-Py serves as a standard substrate in a wide range of studies employing a hyperpolarization technique for efficient polarization transfer from parahydrogen to heteronuclei; this technique, called SABRE (signal amplification by reversible exchange), employs a simultaneous chemical exchange of parahydrogen and a to-be-hyperpolarized substrate (e.g., pyridine) on metal centers. In studies aimed at the development of hyperpolarized contrast agents for in vivo molecular imaging, pyridine is often employed either as a model substrate (for hyperpolarization technique development, quality assurance, and phantom imaging studies) or as a co-substrate to facilitate more efficient hyperpolarization of a wide range of emerging contrast agents (e.g., nicotinamide). Here, the produced N-15-Py was used for the feasibility study of spontaneous N-15 hyperpolarization at high magnetic (HF) fields (7 T and 9.4 T) of an NMR spectrometer and an MRI scanner. SABRE hyperpolarization enabled acquisition of 2D MRI imaging of catalyst-bound N-15-pyridine with 75 x 75 mm(2) field of view (FOV), 32 x 32 matrix size, demonstrating the feasibility of N-15 HF-SABRE molecular imaging with 2.4 x 2.4 mm(2) spatial resolution.