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

[Image: see text] Nicotinamide (a vitamin B(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-(15)N...

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Autores principales: Shchepin, Roman V., Barskiy, Danila A., Mikhaylov, Dmitry M., Chekmenev, Eduard Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2016
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843783/
https://www.ncbi.nlm.nih.gov/pubmed/26999571
http://dx.doi.org/10.1021/acs.bioconjchem.6b00148
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author Shchepin, Roman V.
Barskiy, Danila A.
Mikhaylov, Dmitry M.
Chekmenev, Eduard Y.
author_facet Shchepin, Roman V.
Barskiy, Danila A.
Mikhaylov, Dmitry M.
Chekmenev, Eduard Y.
author_sort Shchepin, Roman V.
collection PubMed
description [Image: see text] Nicotinamide (a vitamin B(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-(15)N with an excellent isotopic purity (98%) and good yield (55%). (15)N nuclear spin label in nicotinamide-1-(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-(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-(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 (15)N-enriched N-heterocycles that can be used as hyperpolarized contrast agents for future in vivo molecular imaging studies.
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spelling pubmed-48437832017-03-21 Efficient Synthesis of Nicotinamide-1-(15)N for Ultrafast NMR Hyperpolarization Using Parahydrogen Shchepin, Roman V. Barskiy, Danila A. Mikhaylov, Dmitry M. Chekmenev, Eduard Y. Bioconjug Chem [Image: see text] Nicotinamide (a vitamin B(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-(15)N with an excellent isotopic purity (98%) and good yield (55%). (15)N nuclear spin label in nicotinamide-1-(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-(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-(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 (15)N-enriched N-heterocycles that can be used as hyperpolarized contrast agents for future in vivo molecular imaging studies. American Chemical Society 2016-03-21 2016-04-20 /pmc/articles/PMC4843783/ /pubmed/26999571 http://dx.doi.org/10.1021/acs.bioconjchem.6b00148 Text en Copyright © 2016 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Shchepin, Roman V.
Barskiy, Danila A.
Mikhaylov, Dmitry M.
Chekmenev, Eduard Y.
Efficient Synthesis of Nicotinamide-1-(15)N for Ultrafast NMR Hyperpolarization Using Parahydrogen
title Efficient Synthesis of Nicotinamide-1-(15)N for Ultrafast NMR Hyperpolarization Using Parahydrogen
title_full Efficient Synthesis of Nicotinamide-1-(15)N for Ultrafast NMR Hyperpolarization Using Parahydrogen
title_fullStr Efficient Synthesis of Nicotinamide-1-(15)N for Ultrafast NMR Hyperpolarization Using Parahydrogen
title_full_unstemmed Efficient Synthesis of Nicotinamide-1-(15)N for Ultrafast NMR Hyperpolarization Using Parahydrogen
title_short Efficient Synthesis of Nicotinamide-1-(15)N for Ultrafast NMR Hyperpolarization Using Parahydrogen
title_sort efficient synthesis of nicotinamide-1-(15)n for ultrafast nmr hyperpolarization using parahydrogen
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843783/
https://www.ncbi.nlm.nih.gov/pubmed/26999571
http://dx.doi.org/10.1021/acs.bioconjchem.6b00148
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