Copper‐Catalyzed Radical Silylarylation of Activated Alkenes: Preparation of β‐Silyl Amide‐Pharmaceutical Hybrids

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(6), P. 1325 - 1330

Published: Feb. 2, 2024

Abstract Copper‐catalyzed silylarylation of N ‐(arylsulfonyl)acrylamides via a tandem silyl radical addition/1,4‐aryl migration/desulfonylation sequence has been developed. This method employs silanes as the precursor and di‐ tert ‐butyl peroxide (DTBP) initiator. By using this cascade procedure, series β ‐silyl amide‐pharmaceutical hybrids which contain an α ‐all‐carbon quaternary stereocenter were facilely synthesized.

Language: Английский

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EDA Complex-Enabled Annulation to Access CF₂-Containing Tetralones and Quinazolinones Using Persulfates as Electron Donors

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(15), P. 10614 - 10623

Published: July 25, 2024

A photocatalyst-free and EDA complex-enabled radical cascade cyclization reaction of inactive alkenes with bromodifluoroacetamides was reported for the divergent synthesis fluorine-containing tetralones quinazolinones. In this transformation, persulfates as electron donors difluoro bromamide acceptors generate complex. This is a promising photochemical method advantages such mild conditions, simple operation, being metal-free, excellent functional group tolerance.

Language: Английский

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Applications of Machine Learning Approaches for the Discovery of SARS-CoV-2 PLpro Inhibitors

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

The global impact of SARS-CoV-2 highlights the need for treatments beyond vaccination, given limited availability effective medications. While Pfizer introduced Paxlovid, an FDA-approved antiviral targeting main protease (Mpro), this study focuses on designing new antivirals against another protease, papain-like (PLpro), which is crucial viral replication and immune suppression. NCATS/NIH performed a high-throughput screen ∼15,000 molecules from internal molecular library, identifying initial hits with 0.5% success rate. To improve hit rate identify potent inhibitors, machine learning-based virtual screens were applied to ∼150,000 compounds, yielding 125 top predicted hits. Biochemical evaluation revealed 25 promising 20% hit-rate IC50 values 1.75 μM <36 across 13 chemotypes. Further analog screening those chemotypes, as part structure–activity relationships, led 20 additional Additionally, hit-to-lead optimization chemotype 7 produced 10 more analogs. These PLpro inhibitors provide templates development COVID-19.

Language: Английский

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Semiheterogeneous Photoredox Catalysis: Synthesis of 3-Sulfonylquinolines via Radical Multicomponent Cascade Annulation

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(18), P. 13782 - 13788

Published: Sept. 2, 2024

An efficient photocatalytic protocol combining heterogeneous semiconductors as photocatalysts and NHPI a redox reagent was disclosed. Under this protocol, 3-sulfonylquinolines were formed in up to 92% yield via multicomponent radical cascade annulation. Good substituent tolerance gram-scale reaction showed the potential fine chemicals modification pharmaceutical synthesis.

Language: Английский

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Electron-Donor-Mediated Divergent Transformation of Br–R_F via EDA Complex for the Synthesis of Fluorine-Containing Oxindoles and Amides

Organic Letters, Journal Year: 2024, Volume and Issue: 26(46), P. 9990 - 9995

Published: Nov. 11, 2024

We have developed an unprecedented electron-donor-controlled divergent reaction between

Language: Английский

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Construction of Thiochroman-4-ols through a (4 + 2) Annulation Strategy Using Allenyl Sulfones as Substrates

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Herein, we report an efficient and straightforward access to highly functionalized thiochroman-4-ol derivatives by the construction of S-C C-C bonds in a domino fashion. The methodology is based on (4 + 2) annulation reaction involving α-substituted allenyl sulfones aromatic thiolates displaying ortho α-ketoester group as substrates. anionic sulfur species were generated situ reduction corresponding disulfides, using Rongalite/K2CO3 system. practicality strategy was further demonstrated gram-scale synthesis, postmodifications, compatibility with other types electron-deficient allenes (allenoate allenone).

Language: Английский

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Access to quaternary-carbon-containing β-alkyl amides via persulfate-promoted domino alkylation/smiles rearrangement of alkenes

RSC Advances, Journal Year: 2025, Volume and Issue: 15(20), P. 16183 - 16186

Published: Jan. 1, 2025

An efficient radical alkylative annulation/arylation of N -(arylsulfonyl)acrylamide with 4-alkyl-1,4-dihydropyridines (DHP) was developed for synthesizing all-carbon quaternary-centered β-alkyl amides.

Language: Английский

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Photoinduced Metal‐Free Decarboxylative Fluoroalkylation of Alkenes for the Synthesis of N‐Arylbutanamides and Oxindoles

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(68)

Published: Aug. 28, 2024

The visible light-induced decarboxylative cascade reaction of fluoroalkyl carboxylic acids has been achieved for the efficient synthesis fluorinated compounds. However, most transformations rely on noble iridium metal complex. Herein, a metal-free realized. This protocol features simple operation, transition free, and good functional group tolerance.

Language: Английский

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Synthesis of Indenones via Persulfate Promoted Radical Alkylation/Cyclization of Biaryl Ynones with 1,4-Dihydropyridines

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 458 - 458

Published: Jan. 17, 2024

The oxidative radical cascade cyclization of alkynes has emerged as a versatile strategy for the efficient construction diverse structural units and complex molecules in organic chemistry. This work reports an alkyl initiated 5-exo-trig biaryl ynones with 1,4-dihydropyridines to selectively synthesize indenones.

Language: Английский

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Electrochemical Trifluoromethylthiolation/Cyclization of N-Arylacrylamides with AgSCF₃: Access to SCF₃-Containing Oxindoles

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(17), P. 11950 - 11958

Published: Aug. 19, 2024

An environmentally friendly electrochemical strategy for the synthesis of SCF3-containing oxindoles was developed. This transformation accomplished through a cascade trifluoromethylthiolation/cyclization N-acrylamides with AgSCF3, obviating requirement external oxidants. A variety functional groups were well tolerated in this transformation.

Language: Английский

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