Efficient Synthesis of Nicotinamide-1-^sup 15^N for Ultrafast NMR Hyperpolarization Using Parahydrogen

Nicotinamide (a vitamin B^sub 3^ amide) is one of the key vitamins as well as a drug for treatment of M. tuberculosis, HIV, cancer, and other diseases. Here, an improved Zincke reaction methodology is presented allowing for straightforward and scalable synthesis of nicotinamide-1-^sup 15^N with an e...

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Bibliographic Details
Published in:Bioconjugate chemistry 2016-04, Vol.27 (4), p.878
Main Authors: Shchepin, Roman V, Barskiy, Danila A, Mikhaylov, Dmitry M, Chekmenev, Eduard Y
Format: Article
Language:English
Subjects:
Chemical reactions
Chemical synthesis
NMR
Nuclear magnetic resonance
Vitamins
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Summary:Nicotinamide (a vitamin B^sub 3^ amide) is one of the key vitamins as well as a drug for treatment of M. tuberculosis, HIV, cancer, and other diseases. Here, an improved Zincke reaction methodology is presented allowing for straightforward and scalable synthesis of nicotinamide-1-^sup 15^N with an excellent isotopic purity (98%) and good yield (55%). ^sup 15^N nuclear spin label in nicotinamide-1-^sup 15^N can be NMR hyperpolarized in seconds using parahydrogen gas. NMR hyperpolarization using the process of temporary conjugation between parahydrogen and to-be-hyperpolarized biomolecule on hexacoordinate iridium complex via the Signal Amplification By Reversible Exchange (SABRE) method significantly increases detection sensitivity (e.g., >20 000-fold for nicotinamide-1-^sup 15^N at 9.4 T) as has been shown by Theis T. et al. (J. Am. Chem. Soc. 2015, 137, 1404), and hyperpolarized in this fashion, nicotinamide-1-^sup 15^N can be potentially used to probe metabolic processes in vivo in future studies. Moreover, the presented synthetic methodology utilizes mild reaction conditions, and therefore can also be potentially applied to synthesis of a wide range of ^sup 15^N-enriched N-heterocycles that can be used as hyperpolarized contrast agents for future in vivo molecular imaging studies.
ISSN:1043-1802
1520-4812