Synthesis of 15N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates DOI Creative Commons
Hillary M. H. Nguyen, D. Thomas, Marie A. Hart

и другие.

Опубликована: Ноя. 2, 2023

Methods to incorporate stable radioisotopes are integral pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods 15N-atoms within their structures limited. Here, we present a general approach pyridine 15N-labeling that proceeds via ring-opening NTf-Zincke imines then ring-closure with commercially available 15NH4Cl salts. This process functions on range substituted pyridines, from simple building block-type compounds late-stage labeling complex pharmaceuticals, 15N-incorporation is >95% most cases. The reactivity Zincke imine intermediates also enables deuteration C3- C5-positions, resulting higher mass isotopologs required for LCMS analysis biological fluids during drug

Язык: Английский

15NRORC: An Azine Labeling Protocol DOI

Zachary A. Tolchin,

Joel M. Smith

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(5), С. 2939 - 2943

Опубликована: Янв. 12, 2024

A practical method for the synthesis of 15N-labeled azines with a high degree isotopic enrichment is described. Activation azine heterocycles an electron-deficient arene allows facile substitution nitrogen atom specifically designed reagent that undergoes canonical ANRORC-type mechanism. wide range can be converted to their corresponding 15N isotopologs using this method, and it also dearomative access reduced heterocyclic congeners. short formal 15N-solifenacin accomplished as well demonstrate application generating labeled pharmaceuticals.

Язык: Английский

Процитировано

25
Synthesis of 15N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates DOI
Hillary M. H. Nguyen, D. Thomas, Marie A. Hart

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(5), С. 2944 - 2949

Опубликована: Янв. 16, 2024

Methods to incorporate stable radioisotopes are integral pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods 15N atoms within their structures limited. Here, we present a general approach pyridine 15N-labeling that proceeds via ring-opening NTf-Zincke imines then ring-closure with commercially available 15NH4Cl salts. This process functions on range substituted pyridines, from simple building block-type compounds late-stage labeling complex pharmaceuticals, 15N-incorporation is >95% most cases. The reactivity Zincke imine intermediates also enables deuteration C3- C5-positions, resulting higher mass isotopologs required for LCMS analysis biological fluids during drug

Язык: Английский

Процитировано

21
Pyridine-based Strategy towards Nitrogen Isotope Exchange DOI Creative Commons
Minghao Feng,

Maylis Norlöff,

Benoit Guichard

и другие.

Опубликована: Окт. 31, 2023

Isotopic labeling is at the core of health and life science applications such as nuclear imaging, pharmacokinetics bio-distribution studies plays a central role in drug development. The rapid access to isotopically labeled organic molecules sine qua non condition support these societally vital areas research. Despite relevance pyridine biologically active scaffold, nitrogen-13 this scaffold remains elusive an almost prohibited challenge for radio-labelling (+ emitter, T1/2 9.97 min), despite its positron emission tomography. Based on rationally driven approach, study presents innovative solution pyridines by nitrogen isotope exchange reaction based Zincke activation strategy. technology conceptualizes new opportunity field labeling. 15N-labeling other heterocycles pyrimidines isoquinolines was provided large set derivatives including structurally elaborated pharmaceuticals. Using [13N]NH3 primary source, proof-of-concept achieve examples 13N-labeling pyridines. We believe method will play fundamental future developments 13N-based PET radiotracers.

Язык: Английский

Процитировано

6
Combining Umpolung and Carbon Isotope Exchange Strategies for Accessing Isotopically Labeled α-Keto Acids DOI

Jingran Ning,

Baoyang Du,

Shilong Cao

и другие.

Organic Letters, Год журнала: 2024, Номер 26(28), С. 5966 - 5971

Опубликована: Июль 3, 2024

The integration of umpolung and carbon isotope exchange for accessing isotopically labeled α-keto acids through photoredox catalysis is elucidated. This process involves the carbonyl C(sp

Язык: Английский

Процитировано

1
Heterocyclic Surgery for Isotopic Labeling DOI
Joel M. Smith

Synlett, Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Abstract Recent developments in the isotopic labeling of heteroarenes may prove to be useful realms biomedical science, materials chemistry, and fundamental organic chemistry. The use age-old Zincke reaction, or tactical variants thereof, has become particularly utilitarian effecting single-atom nitrogen replacement various azines generate their desired isotopologues. This chemistry can synthetically leveraged at an early stage for diversity-oriented heterocyclic pharmaceuticals and/or natural products. Additionally, given prevalence saturated azacycles biologically relevant molecules, access these isotopologues becomes through dearomative retrosynthetic analysis from corresponding 15N-labeled heteroarenes. 1 Introduction 2 Our Lab’s Development 15NRORC Reaction 3 Other Azine-Labeling Methods 4 Expanded ANRORC Utilization 5 Conclusion Outlook

Язык: Английский

Процитировано

0
Synthesis of 15N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates DOI Creative Commons
Hillary M. H. Nguyen, D. Thomas, Marie A. Hart

и другие.

Опубликована: Ноя. 2, 2023

Methods to incorporate stable radioisotopes are integral pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods 15N-atoms within their structures limited. Here, we present a general approach pyridine 15N-labeling that proceeds via ring-opening NTf-Zincke imines then ring-closure with commercially available 15NH4Cl salts. This process functions on range substituted pyridines, from simple building block-type compounds late-stage labeling complex pharmaceuticals, 15N-incorporation is >95% most cases. The reactivity Zincke imine intermediates also enables deuteration C3- C5-positions, resulting higher mass isotopologs required for LCMS analysis biological fluids during drug

Язык: Английский

Процитировано

0