A Photocaged, Water-Oxidizing, and Nucleolus-Targeted Pt(IV) Complex with a Distinct Anticancer Mechanism

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(17), P. 7803 - 7812

Published: March 27, 2020

Targeted anticancer prodrugs that can be controllably activated are highly desired for personalized precision medicine in cancer therapy. Such with unique action modes also promising to overcome drug resistance. Herein, we report coumaplatin, an oxaliplatin-based and photocaged Pt(IV) prodrug, realize nuclear accumulation along "on-demand" activation. This prodrug is based on a complex efficiently photoactivated via water oxidation without the requirement of reducing agent. Coumaplatin accumulates very nucleoli, upon photoactivation, this exhibits level photocytotoxicity up 2 orders magnitude higher than oxaliplatin. Unexpectedly, presents strikingly enhanced tumor penetration ability utilizes distinct mode resistance; i.e., coumaplatin but not oxaliplatin induces cell senescence, p53-independent death, immunogenic death T Our findings only provide novel strategy rational design nucleolus-targeted demonstrate accumulating conventional platinum drugs nucleus practical way change its canonical mechanism achieve reduced

Language: Английский

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Divergent Iron‐Catalyzed Coupling of O‐Acyloximes with Silyl Enol Ethers

Chemistry - A European Journal, Journal Year: 2016, Volume and Issue: 23(8), P. 1779 - 1783

Published: Dec. 20, 2016

An iron-catalyzed coupling reaction of O-acyloximes and O-benzoyl amidoximes with silyl enol ethers is reported. The protocol provides access to functionalized pyrroles, 1,6-ketonitriles, pyrrolines imidazolines via carbon-centered radicals generated from an initially formed iminyl radical. intramolecular cyclization ring-opening processes the radical take place preferentially over reactions that proceed through a 1,3-hydrogen transfer, providing insights into oxime derivatives. cheap environmentally friendly iron catalyst, broad substrate scope functional group compatibility make this useful for synthesis valuable nitrogen-containing products.

Language: Английский

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Organic Synthesis Using Nitroxides

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(16), P. 10302 - 10380

Published: Aug. 14, 2023

Nitroxides, also known as nitroxyl radicals, are long-lived or stable radicals with the general structure R1R2N–O•. The spin distribution over nitroxide N and O atoms contributes to thermodynamic stability of these radicals. presence bulky N-substituents R1 R2 prevents radical dimerization, ensuring their kinetic stability. Despite reactivity toward various transient C some nitroxides can be easily stored under air at room temperature. Furthermore, oxidized oxoammonium salts (R1R2N═O+) reduced anions (R1R2N–O–), enabling them act valuable oxidants reductants depending on oxidation state. Therefore, they exhibit interesting across all three states. Due fascinating properties, find extensive applications in diverse fields such biochemistry, medicinal chemistry, materials science, organic synthesis. This review focuses versatile For use other important fields, we will refer several articles. introductory part provides a brief overview history chemistry. Subsequently, key methods for preparing discussed, followed by an examination structural diversity physical properties. main portion this is dedicated reactions, wherein parent corresponding serve active species. It demonstrated that functional groups (such alcohols, amines, enolates, alkanes among others) efficiently oxidized. These oxidations carried out using catalysts combination stoichiometric terminal oxidants. By reducing anions, become effective reagents intriguing Nitroxides possess ability selectively react making useful terminating cascade reactions forming alkoxyamines. Depending structure, alkoxyamines weak C–O bonds, allowing thermal generation through reversible bond cleavage. Such thermally generated participate transformations, discussed end review. application strategy natural product synthesis presented.

Language: Английский

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Direct C–H Cyanoalkylation of Heteroaromatic N-Oxides and Quinones via C–C Bond Cleavage of Cyclobutanone Oximes

Organic Letters, Journal Year: 2017, Volume and Issue: 19(21), P. 5908 - 5911

Published: Oct. 26, 2017

A direct C–H cyanoalkylation of heteroaromatic N-oxides and quinones with cyclobutanone oximes is reported. This redox-neutral, operationally simple reaction successfully amenable to a wide range N-oxides, quinones, oximes. novel catalytic system consisting nickel source proved crucial for cleavage the C–C bond selective formation over β-hydride elimination. Mechanistic studies suggest that radical intermediate might be involved in this transformation.

Language: Английский

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Synthesis of Sterically Hindered Primary Amines by Concurrent Tandem Photoredox Catalysis

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(2), P. 987 - 998

Published: Jan. 6, 2020

Primary amines are an important structural motif in active pharmaceutical ingredients (APIs) and intermediates thereof, as well members of ligand libraries for either biological or catalytic applications. Many chemical methodologies exist amine synthesis, but the direct synthesis primary with a fully substituted α carbon center is underdeveloped area. We report method which utilizes photoredox catalysis to couple readily available O-benzoyl oximes cyanoarenes synthesize α-carbons. also demonstrate that this enables α-trifluoromethyl functionality. Based on experimental computational results, we propose mechanism where photocatalyst engages concurrent tandem by reacting oxime triplet sensitizer first cycle reductant toward cyanoarene second achieve hindered via heterocoupling radicals from oximes.

Language: Английский

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Visible-Light-Promoted Carboimination of Unactivated Alkenes for the Synthesis of Densely Functionalized Pyrroline Derivatives

ACS Catalysis, Journal Year: 2016, Volume and Issue: 6(8), P. 5571 - 5574

Published: July 18, 2016

An efficient strategy which integrates visible-light-induced iminyl-radical formation with carboimination of unactivated alkenes has been developed for the easy access densely functionalized pyrroline derivatives. With fac-[Ir(ppy)3] as photoredox catalyst, acyl oximes were converted into iminyl radical intermediates by one electron reduction, and evolve through a cascade intramolecular cyclization intermolecular carbon trapping to give pyrrolines. The utilization silyl enol ethers coupling partners not only allows introduction synthetically useful ketone functionalities but also renders catalyst regeneration without any external reductants. This protocol is characterized its mild reaction conditions tolerance broad range functionalities.

Language: Английский

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Recent advances in iminyl radical-mediated catalytic cyclizations and ring-opening reactions

New Journal of Chemistry, Journal Year: 2019, Volume and Issue: 43(8), P. 3254 - 3264

Published: Jan. 1, 2019

Iminyl radicals have emerged as versatile synthons for N-heterocycle constructions and ring-opening reactions.

Language: Английский

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Recent advances in cyclization reactions of unsaturated oxime esters (ethers): synthesis of versatile functionalized nitrogen-containing scaffolds

Organic Chemistry Frontiers, Journal Year: 2020, Volume and Issue: 7(14), P. 1948 - 1969

Published: Jan. 1, 2020

We summarized recent advances in cyclization reactions of unsaturated oxime esters (ethers), which provide diversiform functionalized nitrogen-containing scaffolds.

Language: Английский

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Visible-light-promoted iminyl radical formation from vinyl azides: synthesis of 6-(fluoro)alkylated phenanthridines

Chemical Communications, Journal Year: 2016, Volume and Issue: 52(72), P. 10898 - 10901

Published: Jan. 1, 2016

An efficient strategy assisted by visible-light-promoted iminyl radical formation has been developed for the synthesis of 6-(fluoro)alkylated phenanthridine derivatives.

Language: Английский

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Functionalised Oximes: Emergent Precursors for Carbon-, Nitrogen- and Oxygen-Centred Radicals

Molecules, Journal Year: 2016, Volume and Issue: 21(1), P. 63 - 63

Published: Jan. 7, 2016

Oxime derivatives are easily made, non-hazardous and have long shelf lives. They contain weak N–O bonds that undergo homolytic scission, on appropriate thermal or photochemical stimulus, to initially release a pair of N- O-centred radicals. This article reviews the use these precursors for studying structures, reactions kinetics released Two classes been exploited radical generation; one comprises carbonyl oximes, principally oxime esters amides, second ethers. Both an iminyl together with equal amount oxygen-centred radical. The radicals derived from oximes decarboxylate giving access variety carbon-centred nitrogen-centred species. Methods developed homolytically dissociating include UV irradiation, conventional microwave heating. Photoredox catalytic methods succeed well specially functionalised this aspect is also reviewed. Attention drawn key contributions made by EPR spectroscopy, aided DFT computations, in elucidating structures dynamics transient intermediates.

Language: Английский

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