Photons or Electrons? A Critical Comparison of Electrochemistry and Photoredox Catalysis for Organic Synthesis

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(2), P. 2487 - 2649

Published: Nov. 9, 2021

Redox processes are at the heart of synthetic methods that rely on either electrochemistry or photoredox catalysis, but how do and catalysis compare? Both approaches provide access to high energy intermediates (e.g., radicals) enable bond formations not constrained by rules ionic 2 electron (e) mechanisms. Instead, they 1e mechanisms capable bypassing electronic steric limitations protecting group requirements, thus enabling chemists disconnect molecules in new different ways. However, while providing similar intermediates, differ several physical chemistry principles. Understanding those differences can be key designing transformations forging disconnections. This review aims highlight these similarities between comparing their underlying principles describing impact electrochemical photochemical methods.

Language: Английский

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Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(20), P. 4996 - 4996

Published: Oct. 9, 2019

Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication proteins nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery treat different kinds infections, taking advantage difference when compared with human cells. However, resistances compounds emerged then only combined therapies are currently clinic. addition, some found immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim review provide updated state-of-the-art on use antifolates antibacterial immunomodulating agents clinical setting, well present action mechanisms investigated biomedical applications.

Language: Английский

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Silyl Radical-Mediated Activation of Sulfamoyl Chlorides Enables Direct Access to Aliphatic Sulfonamides from Alkenes

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 142(2), P. 720 - 725

Published: Dec. 27, 2019

Single electron reduction is more challenging for sulfamoyl chlorides than sulfonyl chlorides. However, and can be easily activated by Cl-atom abstraction a silyl radical with similar rates. This latter mode of activation was therefore selected to access aliphatic sulfonamides, applying single-step hydrosulfamoylation using inexpensive olefins, tris(trimethylsilyl)silane, photocatalyst Eosin Y. late-stage functionalization protocol generates molecules as complex sulfonamide-containing cyclobutyl-spirooxindoles direct use in medicinal chemistry.

Language: Английский

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Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α‐Glycosidase and Cholinesterase Inhibitors

Chemistry & Biodiversity, Journal Year: 2021, Volume and Issue: 18(4)

Published: Feb. 23, 2021

Abstract A series of six N ‐carbamimidoyl‐4‐(3‐substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects the novel ureido‐substituted investigated spectrophotometric methods for α‐glycosidase (α‐GLY), acetylcholinesterase (AChE), butyrylcholinesterase (BChE) enzymes associated diabetes mellitus (DM) Alzheimer's disease (AD). ‐Carbamimidoyl‐4‐{[(3,4‐dichlorophenyl)carbamoyl]amino}benzene‐1‐sulfonamide ( 2f ) showed AChE BChE effects, K I values 515.98±45.03 nM 598.47±59.18 nM, respectively, while ‐carbamimidoyl‐4‐{[(3‐chlorophenyl)carbamoyl]amino}benzene‐1‐sulfonamide 2e strong α‐GLY effect, 103.94±13.06 nM. The antidiabetic compounds are higher than their anti‐Alzheimer's because inhibition effect on diabetic enzyme is greater esterase enzymes. Indeed, metabolic important treatment DM AD.

Language: Английский

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Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors

Journal of Biomolecular Structure and Dynamics, Journal Year: 2021, Volume and Issue: 40(19), P. 8752 - 8764

Published: May 5, 2021

The underlying cause of many metabolic diseases is abnormal changes in enzyme activity metabolism. Inhibition enzymes such as cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) α-glucosidase (α-GLY) one the accepted approaches treatment Alzheimer's disease (AD) diabetes mellitus (DM). Here we reported an investigation a new series novel ureido-substituted derivatives with sulfamethazine backbone (2a-f) for inhibition AChE, BChE, α-GLY. All demonstrated nanomolar levels α-GLY inhibitors KI values range 56.07-204.95 nM, 38.05-147.04 12.80-79.22 respectively. Among strong N-(4,6-dimethylpyrimidin-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide detected against ChEs, compound 2c, 4-fluorophenylureido derivative, most potent profile towards BChE. A comprehensive ligand/receptor interaction prediction was performed silico three providing molecular docking using Glide XP, MM-GBSA, ADME-Tox modules. present research reinforces rationale behind utilizing innovative anticholinergic antidiabetic agents mechanism action, submitting propositions rational design synthesis targeting ChEs α-GLY.Communicated by Ramaswamy H. Sarma.

Language: Английский

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Comparing biochar- and bentonite-supported Fe-based catalysts for selective degradation of antibiotics: Mechanisms and pathway

Environmental Research, Journal Year: 2020, Volume and Issue: 183, P. 109156 - 109156

Published: Jan. 22, 2020

Language: Английский

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A Broad‐Spectrum Catalytic Amidation of Sulfonyl Fluorides and Fluorosulfates**

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(13), P. 7397 - 7404

Published: Dec. 18, 2020

Abstract A broad‐spectrum, catalytic method has been developed for the synthesis of sulfonamides and sulfamates. With activation by combination a amount 1‐hydroxybenzotriazole (HOBt) silicon additives, amidations sulfonyl fluorides fluorosulfates proceeded smoothly excellent yields were generally obtained (87–99 %). Noticeably, this protocol is particularly efficient sterically hindered substrates. Catalyst loading low only 0.02 mol % catalyst required multidecagram‐scale an amantadine derivative. In addition, potential in medicinal chemistry demonstrated marketed drug Fedratinib via key intermediate fluoride 13 . Since large number amines are commercially available, route provides facile entry to access analogues biological screening.

Language: Английский

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Phosphine/Photoredox Catalyzed Anti-Markovnikov Hydroamination of Olefins with Primary Sulfonamides via α-Scission from Phosphoranyl Radicals

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(43), P. 18331 - 18338

Published: Oct. 21, 2021

New strategies to access radicals from common feedstock chemicals hold the potential broadly impact synthetic chemistry. We report a dual phosphine and photoredox catalytic system that enables direct formation of sulfonamidyl primary sulfonamides. Mechanistic investigations support N-centered radical is generated via α-scission P-N bond phosphoranyl intermediate, formed by sulfonamide nucleophilic addition cation. As compared recently well-explored β-scission chemistry radicals, this strategy applicable activation N-based nucleophiles in phosphine. highlight application an intermolecular anti-Markovnikov hydroamination unactivated olefins with A range structurally diverse secondary sulfonamides can be prepared good excellent yields under mild conditions.

Language: Английский

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The Chosen Few: Parallel Library Reaction Methodologies for Drug Discovery

The Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 87(4), P. 1880 - 1897

Published: Nov. 15, 2021

Parallel library synthesis is an important tool for drug discovery because it enables the of closely related analogues in parallel via robust and general synthetic transformations. In this perspective, we analyzed methodologies used >5000 libraries representing 15 prevalent The data set contains complex substrates diverse arrays building blocks over last 14 years at AbbVie. that have demonstrated robustness generality with proven success are described along their substrate scopes. evolution past decade discussed. We also highlight combination high-throughput experimentation will continue to facilitate library-amenable discovery.

Language: Английский

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Ni/Photoredox-Catalyzed C(sp³)–C(sp³) Coupling between Aziridines and Acetals as Alcohol-Derived Alkyl Radical Precursors

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(43), P. 20067 - 20077

Published: Oct. 18, 2022

Aziridines are readily available C(sp3) precursors that afford valuable β-functionalized amines upon ring opening. In this article, we report a Ni/photoredox methodology for C(sp3)-C(sp3) cross-coupling between aziridines and methyl/1°/2° aliphatic alcohols activated as benzaldehyde dialkyl acetals. Orthogonal activation modes of each alkyl coupling partner facilitate cross-selectivity in the bond-forming reaction: acetal is via hydrogen atom abstraction β-scission bromine radical (generated situ from single-electron oxidation bromide), whereas aziridine at Ni center reduction. We demonstrate an Ni(II) azametallacycle, conventionally proposed cross-coupling, not intermediate productive cross-coupling. Rather, stoichiometric organometallic linear free energy relationship studies indicate proceeds Ni(I) oxidative addition, previously unexplored elementary step.

Language: Английский

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