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

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• 作者：Roman V. Shchepin ; Danila A. Barskiy ; Dmitry M. Mikhaylov ; Eduard Y. Chekmenev
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：April 20, 2016
• 年：2016
• 卷：27
• 期：4
• 页码：878-882
• 全文大小：351K
• 年卷期：0
• ISSN：1520-4812

文摘

Nicotinamide (a vitamin B₃ 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-1-¹⁵N with an excellent isotopic purity (98%) and good yield (55%). ¹⁵N nuclear spin label in nicotinamide-1-¹⁵N 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-1-¹⁵N 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-1-¹⁵N 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 ¹⁵N-enriched N-heterocycles that can be used as hyperpolarized contrast agents for future in vivo molecular imaging studies.