Pyridine-based strategies towards nitrogen isotope exchange and multiple isotope incorporation DOI Creative Commons
Minghao Feng,

Maylis Norlöff,

Benoit Guichard

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 18, 2024

Abstract Isotopic labeling is at the core of health and life science applications such as nuclear imaging, metabolomics 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. Based on rationally driven approach, this study presents an innovative solution pyridines by nitrogen isotope exchange reaction based Zincke activation strategy. technology conceptualizes opportunity field labeling. 15 N-labeling other relevant heterocycles pyrimidines isoquinolines showcases large set derivatives, including pharmaceuticals. Finally, we explore nitrogen-to-carbon strategy order 13 C-labeled phenyl derivatives deuterium mono-substituted benzene from pyridine- 2 H 5 . These results open alternative avenues for multiple aromatic cores.

Язык: Английский

Late-Stage C–H Functionalization of Azines DOI

Celena M. Josephitis,

Hillary M. H. Nguyen, Andrew McNally

и другие.

Chemical Reviews, Год журнала: 2023, Номер 123(12), С. 7655 - 7691

Опубликована: Май 3, 2023

Azines, such as pyridines, quinolines, pyrimidines, and pyridazines, are widespread components of pharmaceuticals. Their occurrence derives from a suite physiochemical properties that match key criteria in drug design is tunable by varying their substituents. Developments synthetic chemistry, therefore, directly impact these efforts, methods can install various groups azine C–H bonds particularly valuable. Furthermore, there growing interest late-stage functionalization (LSF) reactions focus on advanced candidate compounds often complex structures with multiple heterocycles, functional groups, reactive sites. Because factors electron-deficient nature the effects Lewis basic N atom, distinct arene counterparts, application LSF contexts difficult. However, have been many significant advances reactions, this review will describe progress, much which has occurred over past decade. It possible to categorize radical addition processes, metal-catalyzed activation transformations occurring via dearomatized intermediates. Substantial variation reaction within each category indicates both rich reactivity heterocycles creativity approaches involved.

Язык: Английский

Процитировано

111
Carbon-to-nitrogen single-atom transmutation of azaarenes DOI
Jisoo Woo, Colin Stein, Alec H. Christian

и другие.

Nature, Год журнала: 2023, Номер 623(7985), С. 77 - 82

Опубликована: Ноя. 1, 2023

Язык: Английский

Процитировано

93
Recent Advances in Pyridine Scaffold: Focus on Chemistry, Synthesis, and Antibacterial Activities DOI Creative Commons
Md. Badrul Islam, Md. Inshaful Islam,

Nikhil Nath

и другие.

BioMed Research International, Год журнала: 2023, Номер 2023(1)

Опубликована: Янв. 1, 2023

Multidrug-resistant (MDR) pathogens have created a fatal problem for human health and antimicrobial treatment. Among the currently available antibiotics, many are inactive against MDR pathogens. In this context, heterocyclic compounds/drugs play vital role. Thus, it is very much essential to explore new research combat issue. Of nitrogen-bearing compounds/drugs, pyridine derivatives of special interest due their solubility. Encouragingly, some newly synthesized found inhibit multidrug-resistant S. aureus (MRSA). Pyridine scaffold bearing poor basicity generally improves water solubility in pharmaceutically potential molecules has led discovery numerous broad-spectrum therapeutic agents. Keeping these mind, we reviewed chemistry, recent synthetic techniques, bacterial preventative activity since 2015. This will facilitate development pyridine-based novel antibiotic/drug design near future as versatile with limited side effects next-generation therapeutics.

Язык: Английский

Процитировано

62
Skeletal editing of pyridines through atom-pair swap from CN to CC DOI Creative Commons
Qiang Cheng,

Debkanta Bhattacharya,

Malte Haring

и другие.

Nature Chemistry, Год журнала: 2024, Номер 16(5), С. 741 - 748

Опубликована: Янв. 18, 2024

Abstract Skeletal editing is a straightforward synthetic strategy for precise substitution or rearrangement of atoms in core ring structures complex molecules; it enables quick diversification compounds that not possible by applying peripheral strategies. Previously reported skeletal common arenes mainly relies on carbene- nitrene-type insertion reactions rearrangements. Although powerful, efficient and applicable to late-stage heteroarene structure modification, these strategies cannot be used pyridines. Here we report the direct pyridines through atom-pair swap from CN CC generate benzenes naphthalenes modular fashion. Specifically, use sequential dearomatization, cycloaddition rearomatizing retrocycloaddition one-pot sequence transform parent into bearing diversified substituents at specific sites, as defined reaction components. Applications pyridine cores several drugs are demonstrated.

Язык: Английский

Процитировано

60
meta‐Selective C−H Functionalization of Pyridines DOI
Hui Cao, Qiang Cheng, Armido Studer

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(42)

Опубликована: Апрель 4, 2023

The pyridine moiety is an important core structure for a variety of drugs, agrochemicals, catalysts, and functional materials. Direct functionalization C-H bonds in pyridines straightforward approach to access valuable substituted pyridines. Compared the direct ortho- para-functionalization, meta-selective far more challenging due inherent electronic properties entity. This review summarizes currently available methods meta-C-H using directing group, non-directed metalation, temporary dearomatization strategies. Recent advances ligand control are highlighted. We analyze advantages as well limitations current techniques hope inspire further developments this area.

Язык: Английский

Процитировано

46
14N to 15N Isotopic Exchange of Nitrogen Heteroaromatics through Skeletal Editing DOI
G. Logan Bartholomew,

Samantha L. Kraus,

Lucas J. Karas

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(5), С. 2950 - 2958

Опубликована: Янв. 29, 2024

The selective modification of nitrogen heteroaromatics enables the development new chemical tools and accelerates drug discovery. While methods that focus on expanding or contracting skeletal structures are emerging, for direct exchange single core atoms remain limited. Here, we present a method 14N → 15N isotopic several aromatic heterocycles. This isotope transmutation occurs through activation heteroaromatic substrate by triflylation atom, followed ring-opening/ring-closure sequence mediated 15N-aspartate to effect atom. Key success this transformation is formation an isolable 15N-succinyl intermediate, which undergoes elimination give isotopically labeled heterocycle. These transformations occur under mild conditions in high yields.

Язык: Английский

Процитировано

42
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

27
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

24
A deconstruction-reconstruction strategy for pyrimidine diversification DOI

Benjamin J. H. Uhlenbruck,

Celena M. Josephitis,

Louis de Lescure

и другие.

Nature, Год журнала: 2024, Номер 631(8019), С. 87 - 93

Опубликована: Май 2, 2024

Язык: Английский

Процитировано

20
Asymmetric C3-Allylation of Pyridines DOI
Zhong Liu,

Zhu-Jun Shi,

Lu Liu

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер unknown

Опубликована: Май 17, 2023

Asymmetric intermolecular C–H functionalization of pyridines at C3 is unprecedented. Herein, we report the first examples such transformations: specifically, C3-allylation via tandem borane and iridium catalysis. First, borane-catalyzed pyridine hydroboration generates nucleophilic dihydropyridines; then, dihydropyridine undergoes enantioselective iridium-catalyzed allylation; finally, oxidative aromatization with air as oxidant gives C3-allylated pyridine. This protocol provides direct access to excellent enantioselectivity (up >99% ee) suitable for late-stage pyridine-containing drugs.

Язык: Английский

Процитировано

42