Metal-Catalyzed One-Pot On-DNA Syntheses of Diarylmethane and Thioether Derivatives

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(3), P. 1639 - 1649

Published: Jan. 12, 2022

Metal catalysis, a common approach in conventional organic synthesis, poses challenge DEL chemistry due to the vulnerability of DNA fragments and requirement aqueous media. Here, we describe facile one-pot palladium-catalyzed reaction for formation C(sp2)–C(sp3) C(sp3)–S bonds presence encoding. Using 3, 4-dimethoxybenzenesulfonohydrazide (L8) as bridging reactant, our studies showed that DNA-conjugated benzaldehyde (HP-ArCHO-1), serving precursor, reacted with derivatives iodine, bromine, trifluoromethanesulfonate, disulfides metal-catalyzed chemical transformation afford on-DNA diarylmethanes thioethers. Notably, all reactions displayed wide substrate scopes moderate excellent yields under mild conditions. These greatly expand space DNA-compatible molecular scaffold diversity DNA-encoded libraries.

Language: Английский

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Defluorophosphorylation of fluoroalkyl peroxides for the synthesis of highly substituted furans

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(5), P. 2000 - 2010

Published: Jan. 1, 2023

A highly tunable defluorophosphorylation of fluorinated peroxides for the preparation C 3,4-diphosphoryl furans and 4-monophosphoryl under conditions with no added transition metals is disclosed.

Language: Английский

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Gem-Difluorocyclopropenes as Versatile β-Monofluorinated Three-sp² Carbon Sources for Cp*Rh(III)-Catalyzed [4 + 3] Annulation: Experimental Development and Mechanistic Insight

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(23), P. 14694 - 14701

Published: Nov. 23, 2021

Cp*Rh(III)-catalyzed [4 + 3] annulation of N-methoxy amides for the direct assembly seven-numbered 2H-azepin-2-one frameworks has been realized with gem-difluorocyclopropenes acting as innovative β-monofluorinated three sp2 carbon sources. Either annular arylamides or linear acrylamides embedment various functional groups, including DNA-tagged substrates, were found to be compatible established reaction mode. A redox-neutral Rh(III)–Rh(V)–Rh(III) catalytic cycle, specifically via HOAc-assisted tandem site-/regioselective oxidative addition/reductive elimination/C–F bond cleavage-enabled ring-scission involving unprecedented olefinic C(sp2)–C(sp2) cleavage, deduced based on experimental and computational mechanistic studies. Taken together, our findings not only identified potent efficient coupling partners C–H activation development but also provided a sound basis organic integration transition-metal-catalyzed functionalization cyclopropene fluorine chemistries.

Language: Английский

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A Small Molecule Selected from a DNA‐Encoded Library of Natural Products That Binds to TNF‐α and Attenuates Inflammation In Vivo

Advanced Science, Journal Year: 2022, Volume and Issue: 9(21)

Published: May 21, 2022

Tumor necrosis factor α (TNF-α) inhibitors have shown great success in the treatment of autoimmune diseases. However, to date, approved drugs targeting TNF-α are restricted biological macromolecules, largely due difficulties using small molecules for pharmaceutical intervention protein-protein interactions. Herein power a natural product-enriched DNA-encoded library (nDEL) is exploited identify that interfere with interaction between and cognate receptor. Initially, select capable binding , "late-stage" DNA modification method applied construct an nDEL consisted 400 sterically diverse products pharmaceutically active chemicals. Several products, including kaempferol, identified not only show direct TNF-α, but also lead blockage TNF-α/TNFR1 interaction. Significantly, kaempferol attenuates signaling cells reduces 12-O-tetradecanoylphorbol-13-acetateinduced ear inflammation mice. Structure-activity-relationship analyses demonstrate importance substitution groups at C-3, C-7, C-4' kaempferol. The hit, represents novel chemical scaffold specifically recognizing blocking its signal transduction, promising starting point development molecule inhibitor use clinical setting.

Language: Английский

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Substituted Isocoumarins: An Assemble of Synthetic Strategies Towards 3‐Substituted and 3,4‐Disubstituted Isocoumarins

Chemistry - An Asian Journal, Journal Year: 2023, Volume and Issue: 18(5)

Published: Jan. 17, 2023

The versatility of isocoumarin frameworks offers the privilege to access many pharmacological targets. This unique heterocycle core present in natural products and complex organic molecules contribute medicinal chemistry as anti-cancer, anti-inflammatory immunomodulatory agents. attractive properties exhibited by its analogues urged scientists explore their synthetic analogues. In regard myriads methodologies, we have compiled a review update covering all articles that been published towards synthesis 3-substituted 3,4-disubstituted isocoumarins. Additionally, also highlighted systematic survey catalytic methods for along with scope diverse functionalizations plausible mechanistic aspects.

Language: Английский

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Progress in Transition‐Metal‐Catalyzed Synthesis of Benzo‐Fused Oxygen‐ and Nitrogen Heterocyclic Compounds from Benzoic Acids

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(2), P. 124 - 141

Published: Jan. 10, 2023

Abstract Transition‐metal‐catalyzed oxidative annulation reactions can be used to synthesize various benzo‐fused oxygen‐ and nitrogen‐containing heterocyclic compounds from benzoic acids. This review deals with publications the past 15 years that focus on modifications of reaction conditions variations coupling reagents this end, as well development methods characterized by sustainability, a broad range substrates, high tolerance functional groups in constructing skeletons are commonly found drugs bioactive molecules. summarizes categorizes mechanisms reagents. magnified image

Language: Английский

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Palladium-catalyzed one-pot phosphorylation of phenols mediated by sulfuryl fluoride

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(37), P. 4588 - 4591

Published: Jan. 1, 2021

A one-pot palladium-catalyzed procedure for the synthesis of aryl phosphonates, phosphinates and phosphine oxides from phenols mediated by sulfuryl fluoride.

Language: Английский

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Heterogeneous visible-light promoted dehydrogenative [4 + 2] annulation of benzothioamides and alkynes under aerobic conditions

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(13), P. 5206 - 5212

Published: Jan. 1, 2023

We have developed a visible-light induced dehydrogenative [4 + 2] annulation of benzothioamides and alkynes under aerobic conditions to synthesize isothiochromenes.

Language: Английский

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Experimental and computational journey on transition-metal-catalyzed C H functionalization with fluorinated π-systems

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 522, P. 216244 - 216244

Published: Sept. 24, 2024

Language: Английский

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Indium‐Catalyzed Direct Amidation Reaction of Carboxylic Acids and In Silico Study for Screening the Activity of Potential Therapeutics of the Synthesized Products

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(37)

Published: Oct. 1, 2024

Abstract Amide bonds are ubiquitous and valuable motifs in synthetic chemistry, found a wide range of applications such as the backbone proteins pharmaceutical agents. Thus, environmentally friendly selective methods for synthesizing amide important. Herein, we report simple, efficient, rapid route to access functionalized amides from non‐activated carboxylic acids amines using indium (III) trifluoromethanesulfonate an efficient catalyst. A – including aliphatic, aromatic, heterocyclic, dicarbonyl participate smoothly these reactions, generating structurally diverse moderate good yields (up 91 % 24 examples). The reactions conducted dry tetrahydrofuran (THF) under reflux conditions. Furthermore, this amidation strategy provides method addressing challenging molecules, protected amino acids, produce biocompatible products. These products can then be used substrates various organic transformations, C−H functionalization reactions. We also demonstrate utility our protocol through synthesis essential medicinal chemistry by reacting N ‐protected with 8‐aminoquinoline series biologically compounds. Five products, named 4 f, 4p, 9a, 9c, 9d, have been evaluated in‐silico study. interaction compounds receptor protein 8DQT was examined assess their potential drug candidates hypertension treatment. Effective binding detected between receptor. Data molecular docking studies show that 4d m most active, scores −8.8 −8.6 kcal/mol, respectively. However, compound exhibited stronger affinity than over course dynamic simulation. Our ADMET study suggests all five highly safe body. Based on BOILED‐Egg model study, absorption is suggested they cross blood‐brain barrier.

Language: Английский

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