Late-stage meta-C–H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step

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

Опубликована: Апрель 18, 2024

Catalysed C-H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest medicinal chemistry their beneficial properties applications sp

Язык: Английский

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Excited-State Palladium-Catalyzed Radical Allylic Alkylation: Rapid Access to C2-Allyl Carbohydrates

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 5480 - 5489

Опубликована: Март 19, 2025

Язык: Английский

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Selective Activation of Aromatic C–H Bonds Catalyzed by Single Gold Atoms at Room Temperature

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(46), С. 21389 - 21397

Опубликована: Ноя. 11, 2022

Selective activation and controlled functionalization of C–H bonds in organic molecules is one the most desirable processes synthetic chemistry. Despite progress heterogeneous catalysis using metal surfaces, this goal remains challenging due to stability their ubiquity precursor molecules, hampering regioselectivity. Here, we examine interaction between 9,10-dicyanoanthracene (DCA) Au adatoms on a Ag(111) surface at room temperature (RT). Characterization via low-temperature scanning tunneling microscopy, spectroscopy, noncontact atomic force supported by theoretical calculations, revealed formation organometallic DCA–Au–DCA dimers, where C atoms ends anthracene moieties are bonded covalently single atoms. The compound initiated regioselective cleaving RT. Hybrid quantum mechanics/molecular mechanics calculations show that bond enabled an intermediate metal–organic complex which significantly reduces dissociation barrier specific bond. Harnessing catalytic activity atoms, on-surface reaction RT offers promising routes for future synthesis functional materials.

Язык: Английский

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Fast and Selective β-C–H Borylation of N-Heterocycles with a Supramolecular Iridium Catalyst: Circumventing Deactivation Pathways and Mechanistic Insights

ACS Catalysis, Год журнала: 2023, Номер 13(12), С. 7715 - 7729

Опубликована: Май 24, 2023

Selective iridium-catalyzed C–H bond borylations of unbiased or directing-group-free substrates typically occur under long reaction times and mild temperatures in order to avoid unselective processes including catalyst deactivation. Herein, we describe a supramolecular approach that enables the borylation challenging pyiridines imidazoles very short (up 2 h) with negligible incubation period for activation. The is based on highly rigid zinc–porphyrin substrate-recognition site secondary coordination sphere triazolopyridine chelating fragment attached first at iridium. occurs from substrate located four chemical bonds apart molecular recognition selectivity being exclusively imposed by distance between active regardless nature N,N-chelating coordinating iridium as further supported density functional theory (DFT) calculations. Additional studies (control experiments, nuclear magnetic resonance, single-crystal X-ray diffraction) unraveled key deactivation pathways which up three different partners (water, methoxide ligands precursor, fragment) compete N-heterocycle binding catalyst. This fundamental understanding made possible identification featuring 4-methyl substitution pattern provides suitable balance steric electronic effects both primary spheres, thereby bypassing manifold pathways. DFT calculations indicated importance noncovalent interactions beyond stabilization intermediates transition sates.

Язык: Английский

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Silver‐Free C−H Activation: Strategic Approaches towards Realizing the Full Potential of C−H Activation in Sustainable Organic Synthesis

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(48)

Опубликована: Сен. 5, 2022

The activation of carbon-hydrogen bonds is considered as one the most attractive techniques in synthetic organic chemistry because it bears potential to shorten routes well produce complementary product scopes compared traditional strategies. However, many current methods employ silver salts additives, leading stoichiometric metal waste and thereby preventing full C-H be exploited. Therefore, development silver-free protocols has recently received increasing attention. Mechanistically, can serve various roles thus, avoiding use requires different approaches based on role serves a given process. In this Review, we present comparison silver-based methods. Focusing strategic develop activation, provide reader with means sustainable for activation.

Язык: Английский

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Late‐Stage C−H Activation of Drug (Derivative) Molecules with Pd(ll) Catalysis

Chemistry - A European Journal, Год журнала: 2023, Номер 29(71)

Опубликована: Окт. 17, 2023

Abstract This review comprehensively analyses representative examples of Pd(II)‐catalyzed late‐stage C−H activation reactions and demonstrates their efficacy in converting bonds at multiple positions within drug (derivative) molecules into diverse functional groups. These transformative hold immense potential medicinal chemistry, enabling the efficient selective functionalization specific sites molecules, thereby enhancing pharmacological activity expanding scope candidates. Although notable articles have focused on drug‐like using transition‐metal catalysts, reviews specifically focusing Pd(II) catalysts are required owing to prominence as most widely utilized metal for ability introduce a myriad groups bonds. The utilization Pd‐catalyzed methodologies impressive success introducing various groups, such cyano (CN), fluorine (F), chlorine (Cl), aromatic rings, olefin, alkyl, alkyne, hydroxyl with high regioselectivity functional‐group tolerance. breakthroughs serve invaluable tools discovery development, offering strategic options optimize candidates drive exploration innovative therapeutic solutions.

Язык: Английский

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An update on late-stage functionalization in today’s drug discovery

Expert Opinion on Drug Discovery, Год журнала: 2023, Номер 18(6), С. 597 - 613

Опубликована: Апрель 28, 2023

Introduction Late-stage functionalization (LSF) allows for the introduction of new chemical groups toward end a synthetic sequence, which means molecules can be rapidly accessed without laborious de novo synthesis. Over last decade, medicinal chemists have begun to implement LSF strategies into their drug discovery programs, affording benefits such as efficient access diverse libraries explore structure–activity relationships and improvement physicochemical pharmacokinetic properties.

Язык: Английский

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Highly efficient synthesis of isoxazolones and pyrazolones using g-C3N4·OH nanocomposite with their in silico molecular docking, pharmacokinetics and simulation studies

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 18, 2024

An environmentally friendly, versatile multicomponent reaction for synthesizing isoxazol-5-one and pyrazol-3-one derivatives has been developed, utilizing a freshly prepared g-C

Язык: Английский

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Propargyl Alcohols as Bifunctional Reagents for Divergent Annulations of Biphenylamines via Dual C−H Functionalization/Dual Oxidative Cyclization

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(12)

Опубликована: Дек. 30, 2022

The C-H functionalization strategy provides access to valuable molecules that previously required convoluted synthetic attempts. Dual unsymmetrical functionalization, with a single bifunctional reagent, is an effective tactic. Propargyl alcohols (PAs), despite containing reactive C≡C bond, have not been explored as building blocks via oxidative cleavage. Annulations activation are versatile and synthetically attractive strategy. We disclose PA new reagent for dual of biphenylamine regioselectively annulated outcomes. On tuning the conditions, annulation bifurcated towards unusual cyclization. This method accommodates wide range PAs showcases late-stage diversification some natural products.

Язык: Английский

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Arenes and Heteroarenes C−H Functionalization Under Enabling Conditions: Electrochemistry, Photoelectrochemistry & Flow Technology

The Chemical Record, Год журнала: 2023, Номер 23(10)

Опубликована: Май 31, 2023

Abstract C−H bond functionalization generates molecular complexity in single‐step transformation. However, the activation of bonds requires expensive metals or stoichiometric amounts oxidizing/reducing species. In many cases, they often require pre‐functionalization starting molecules. Such pre‐activating measures cause waste generation and their separation from final product is also troublesome. such a scenario, reactions activating elements generating renewable energy resources as electricity light would be more efficient, green, cost‐effective. Further, incorporation growing flow technology chemical transformation processes will accelerate safer accesses valuable products. Arenes & heteroarenes are ubiquitous pharmaceuticals, natural products, medicinal compounds, other biologically important Herein, we discussed enabling tools technologies used for recent arenes heteroarenes.

Язык: Английский

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