Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(10), С. 7788 - 7824

Опубликована: Май 3, 2024

Triazole demonstrates distinctive physicochemical properties, characterized by weak basicity, various dipole moments, and significant dual hydrogen bond acceptor donor capabilities. These features are poised to play a pivotal role in drug–target interactions. The inherent polarity of triazole contributes its lower logP, suggesting the potential improvement water solubility. metabolic stability adds additional value drug discovery. Moreover, metal-binding capacity nitrogen atom lone pair electrons has broad applications development metal chelators antifungal agents. This Perspective aims underscore unique attributes application. A comparative analysis involving isomers other heterocycles provides guiding insights for subsequent design triazoles, with hope offering valuable considerations designing medicinal chemistry.

Язык: Английский

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Rhodium-Catalyzed [4 + 2]-Annulation of o-Acylanilines with N-Sulfonyl-1,2,3-triazoles: Synthesis of 3-Aminoquinolines

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(13), С. 9077 - 9086

Опубликована: Июнь 23, 2023

Efficient synthesis of 3-aminoquinolines has been demonstrated from readily accessible N-sulfonyl-1,2,3-triazoles and o-acylaniline derivatives. This transformation involves the generation C-C C-N bonds through insertion rhodium azavinyl carbenoid into a N-H bond followed by cyclization aromatization. The important features include good functional group tolerance, indoloquinoline, isolation N-H-inserted product, potential intermediate.

Язык: Английский

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Synthesis of Dihydro-3,1-benzoxazine Derivatives from 1,3-Amino Alcohols and N-Sulfonyl-1,2,3-triazole

Organic Letters, Год журнала: 2023, Номер 25(19), С. 3375 - 3379

Опубликована: Май 8, 2023

An efficient rhodium-catalyzed synthesis of dihydro-3,1-benzoxazine derivatives has been accomplished from aniline-derived 1,3-amino alcohols and N-sulfonyl-1,2,3-triazole. The developed reaction demonstrates the new reactivity azavinyl carbenes allows access to diverse substituted dihydro-3,1-benzoxazines in good yields. Importantly, was readily extended diols could be used for selective protection amino with N-sulfonyl-1,2,3-triazole as protecting reagent.

Язык: Английский

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Metal-Associated Enols as Key Intermediates in Controlling Enantioselectivity in Carbene Insertion Reactions

Synlett, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Abstract Transition-metal-catalysed asymmetric carbene insertion reactions into various X–H bonds typically suffer from poor stereoselectivity. It has been proposed that the presence of metal-free intermediates leads to erosion selectivity. In current account, we discuss our recent efforts understand mechanism and stereochemical model Rh- Fe-catalysed indole phenol. Our detailed DFT calculations show all transformations adopt a common involving an enol intermediate, further tautomerisation which is key stereodetermining step. To account for enantioinduction, propose novel metal-associated species can be solving challenges in reactions. The geometry metal–enol complex interaction between chiral metal prochiral play important roles driving reaction toward particular stereoisomer. 1 Introduction 2 Rh-Catalysed Carbene Insertion Indole 3 Fe-Catalysed C–H Functionalisation 4 O–H 5 Conclusion

Язык: Английский

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Carbonyl vs Hydroxy: Rhodium catalyzed carbonyl ylide triggered diastereoselective synthesis of 2,5-methano-1,3-benzoxazepines

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

A general and efficient rhodium catalyzed chemoselective reaction of N-sulfonyl-1,2,3-triazoles with 2-hydroxyphenyl substituted enone has been successfully accomplished. The occurs through the initial azavinyl carbenes to carbonyl group followed by rearrangement cyclization. tolerated various functional groups allowed synthesis 2,5-methano-1,3-benzoxazepines in high yield as single diastereomer. Control experiments revealed formation potential dihydropyrrole an intermediate aided proposing plausible mechanism.

Язык: Английский

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Reactivity of quinone methides with carbenes generated from α-diazocarbonyl compounds and related compounds

Chemical Communications, Год журнала: 2022, Номер 59(1), С. 29 - 42

Опубликована: Дек. 8, 2022

Over the years, quinone methides have broadly been applied in synthesis and biological systems for synthesizing heterocyclic compounds biologically active molecules. In this feature article, we discussed novel uncovered reactivity of o-quinone methides, p-quinone aza-o-quinone indolyl-2-methides with carbenes generated from α-diazocarbonyl related compounds. Two situ-generated transient intermediates undergo cycloannulation reactions, metathesis-type 1,6-conjugate addition cyclopropanation many other transformations to access nitrogen- oxygen-containing beyond. The is observed various metal catalysts, Brønsted-acids, Lewis acids, phase transfer additives, visible-light-induced transformations.

Язык: Английский

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Efficient synthesis of 3-aminocarbazoles from N-sulfonyl-1,2,3-triazoles and 2-alkenylindole

Journal of Chemical Sciences, Год журнала: 2022, Номер 134(4)

Опубликована: Дек. 13, 2022

Язык: Английский

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A rhodium-catalyzed ylide formation/Smiles rearrangement reaction of chalcogenide ether and triazoles

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(9), С. 2198 - 2203

Опубликована: Янв. 1, 2023

A Rh( ii )-catalyzed highly stereoselective chalcogenide ylide formation/Smiles rearrangement reaction of diaryl thioether/selenoethers and triazoles was successfully developed.

Язык: Английский

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Regiodivergent Synthesis of Oxadiazocines via Dirhodium-Catalyzed Reactivity of Oxazolidines and α-Imino Carbenes

Synlett, Год журнала: 2023, Номер 34(12), С. 1472 - 1476

Опубликована: Апрель 12, 2023

Abstract Using electron-rich or electron-poor N-substituted oxazolidines as substrates, selective formation of either ammonium oxonium ylides is possible in the presence α-imino carbenes. As such, treatment 5-membered oxazolidine precursors with N-sulfonyl-1,2,3-triazoles under dirhodium catalysis (2 mol%) affords regiodivergent synthesis 8-membered 1,3,6- 1,4,6-oxadiazocines upon initial N O reactivity carbene.

Язык: Английский

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Rhodium Catalyzed [4 + 1]-Annulation of o-Acylanilines with 3-Diazoindoline-2-imines

Organic Letters, Год журнала: 2023, Номер 25(34), С. 6357 - 6362

Опубликована: Авг. 21, 2023

An efficient rhodium catalyzed [4 + 1]-annulation of o-acylanilines with 3-diazoindoline-2-imines has been successfully accomplished for the synthesis spiroindolines in good to excellent yield. The reaction occurs through formation N-ylide followed by cyclization and showed tolerance various functional groups. Gram-scale synthesis, diastereoselective construction tetrasubstituted indoline, spirooxindole, isolation potential intermediates have also demonstrated.

Язык: Английский

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