Visible-light-induced cascade reaction: a sustainable approach towards molecular complexity

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(8), P. 1591 - 1628

Published: Jan. 1, 2023

Photoredox catalysis has demonstrated rapid evolution in the field of synthetic organic chemistry. On other hand, splendour cascade reactions providing complex molecular architectures renders them a cutting-edge research area. Therefore, merging photocatalysis with synthesis brings out paradigm immense potential. The development photocascade for target molecule particular skeleton and stereochemical framework presents certain challenges but provides robust environmentally benign alternative. This comprehensive review assembles all accomplishments highlights visible-light-induced literature coverage up to October 2022.

Language: Английский

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Seven-membered N-heterocycles as approved drugs and promising leads in medicinal chemistry as well as the metal-free domino access to their scaffolds

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 275, P. 116556 - 116556

Published: June 5, 2024

Azepanes or azepines are structural motifs of many drugs, drug candidates and evaluated lead compounds. Even though compounds having N-heterocyclic 7-membered rings often found in nature (e.g. alkaloids), the natural this group rather rare as approved therapeutics. Thus, recently studied azepane azepine-congeners predominantly consist semi-synthetically synthetically-obtained scaffolds. In review a comparison drugs investigated leads was proposed taking into regard their aspects (stereochemistry), biological activities, pharmacokinetic properties confirmed molecular targets. The N-heterocycles reveal wide range not only against CNS diseases, but also e.g. antibacterial, anticancer, antiviral, antiparasitic allergy agents. As most potential structures, belonging to N-heterocycles, synthetic scaffolds, report reveals different efficient metal-free cascade approaches useful synthesize both simple azepine-containing congeners those oligocyclic structures. Stereochemistry azepane/azepine fused systems, view data binding with targets, is discussed. Apart from we compare advances SAR studies (mainly 2018 2023), whereas related part concerning various domino strategies focused on last ten years.

Language: Английский

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Tandem Synthesis and Computational Insights into Triazole and Pyrazole-Based Pyridine Derivatives Targeting EGFR-TK in Cancer Therapy

Polycyclic aromatic compounds, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 24

Published: Jan. 8, 2025

Cancer remains one of the leading causes death worldwide, despite significant advances in treatment. Targeting tyrosine kinases, such as epidermal growth factor receptor (EGFR), has become a promising approach for development anticancer agents. In this study, we designed and synthesized series triazole pyrazole-based pyridine derivatives (7a–c, 10a–c, 11, 14a, 14b) to target EGFR-TK. Bioisosteric modifications were incorporated into these compounds, based on key pharmacophoric features established EGFR-TK inhibitors. The compounds evaluated cytotoxicity against range cancer cell lines, including MCF-7, HepG2, HCT116, EA hy926. Notably, 14a 14b, which feature pyrazolo[3,4-b]pyridine-5-carbonitrile nucleus, demonstrated activity with lower IC50 values across all tested lines. These exhibited potent inhibitory effects, indicating their potential effective silico studies, ADME predictions, molecular docking, dynamics simulations, further supported favorable pharmacokinetic profiles strong binding interactions Our findings suggest that could serve candidates targeted therapies.

Language: Английский

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Photochemical Intermolecular Cyclopropanation Reactions of Allylic Alcohols for the Synthesis of [3.1.0]-Bicyclohexanes

Organic Letters, Journal Year: 2023, Volume and Issue: 25(1), P. 169 - 173

Published: Jan. 5, 2023

Cyclopropane-fused lactones are highly desirable in drug and natural products synthesis. Herein, we report on a photochemical, chemoselective reaction of aryldiazoacetates with allylic alcohols that furnishes cyclopropane-fused lactone skeletons efficiently one step. The diastereoselectivity the protocol was precisely controlled, cyclopropanation via free carbene intermediate followed by transesterification constitutes series bicyclic high yield without formation ether byproducts typical O–H insertion reactions.

Language: Английский

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Intramolecular Cascade Cyclization of Cyclobutanone: Asymmetric Construction of Cyclobutanone Fused Oxa-Spirocycles

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

The successful implementation of a cascade reaction involving cyclobutyl unit has posed significant challenge in achieving ring-retentive functionalization because the ring's sacrificial tendency. Herein, we have accomplished cinchona-derived squaramide-catalyzed sequence, encompassing desymmetrization cyclobutanone, followed by an aldol and, subsequently, 1,4-addition step. This overall process offers viable strategy to access architecturally fascinating oxa-spirocycles fused with cyclobutanone motifs good yields high optical purity.

Language: Английский

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Collective Total Synthesis of Aculeatin A, B, D, E, and F

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

Published: Feb. 5, 2025

A collective convergent approach for the enantioselective total synthesis of aculeatins A, B, D, E, and F is presented, featuring [3 + 2]-cycloaddition, iron-mediated reductive N–O bond cleavage, cascade spirocyclization. Moreover, this short six-step strategy supplemented in synthesizing unnatural analogs such as 6-epi-aculeatin F.

Language: Английский

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One-Flask, Telescoped Synthesis of Pyrano[3,2-b]indol-2-ones from O-Nitroynones and β-Ketoesters: Further Advancement to Functionalized Carbazoles

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

Published: March 19, 2025

A new general strategy for accessing pyrano[3,2-b]indol-2-ones, a promising fused hybrid heterocyclic system, has been devised from o-nitroynones and β-ketoesters through one-flask cascade process involving tandem Michael addition, intramolecular cyclization, Cadogan-Sundberg reductive cyclization. The utility of this approach further amplified by leveraging the cycloaddition proclivity α-pyrone moiety in pyrano[3,2-b]indol-2-ones toward concise entry to carbazoles. Illustrative synthesis carbazole natural products hyellazole chlorohyellazole is also disclosed.

Language: Английский

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[RhCp*Cl₂]₂-Catalyzed Indole Functionalization: Synthesis of Bioinspired Indole-Fused Polycycles

ACS Omega, Journal Year: 2023, Volume and Issue: 8(31), P. 27894 - 27919

Published: July 25, 2023

Polycyclic fused indoles are ubiquitous in natural products and pharmaceuticals due to their immense structural diversity biological inference, making them suitable for charting broader chemical space. Indole-based polycycles continue be fascinating as well challenging targets synthetic fabrication because of characteristic frameworks possessing biologically intriguing compounds both origin. As a result, an assortment new processes catalytic routes has been established provide unified access these skeletons very efficient selective manner. Transition-metal-catalyzed processes, particular from rhodium(III), widely used endeavors increase molecular complexity efficiently. In recent years, this resulted significant progress reaching scaffolds with enormous activity based on core indole skeletons. Additionally, Rh(III)-catalyzed direct C–H functionalization benzannulation protocols moieties were one the most alluring techniques generate indole-fused polycyclic molecules This review sheds light developments toward synthesizing by cascade annulation methods using Rh(III)-[RhCp*Cl2]2-catalyzed pathways, which align comprehensive sophisticated field functionalization. Here, we looked at few cascade-based designs catalyzed Rh(III) that produced elaborate inspired bioactivity. The also strongly emphasizes mechanistic insights 1–2, 2–3, 3–4-fused systems, focusing routes. With emphasis efficiency product diversity, chosen carbocycles heterocycles least three fused, bridged, or spiro cages reviewed. newly created synthesis concepts toolkits accessing diazepine, indol-ones, carbazoles, benzo-indoles, illustrative privileged techniques, included featured collection.

Language: Английский

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Substitution controlled aryne insertion: synthesis of diarylmethane/chromones

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(18), P. 2648 - 2651

Published: Jan. 1, 2023

A cascade double aryne insertion reaction was developed to generate a library of diarylmethane scaffolds. Additionally, chromone products were observed in presence an electronegative atom at the ortho position aryne.

Language: Английский

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Catalytic Asymmetric Polycyclization of Tertiary Enamides with Silyl Enol Ethers: Total Synthesis of (−)-Cephalocyclidin A

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(49), P. 26550 - 26556

Published: Nov. 29, 2023

A catalytic enantioselective polycyclization of tertiary enamides with terminal silyl enol ethers has been developed by virtue Cu(OTf)2 catalysis a novel spiropyrroline-derived oxazole (SPDO) ligand. This tandem reaction offers an effective approach to assemble bicyclic and tricyclic N-heterocycles bearing both aza- oxa-quaternary stereogenic centers, which are primal subunits in range natural alkaloids. Strategic application this methodology late-stage radical cyclization as key steps have showcased the concise total synthesis (−)-cephalocyclidin A.

Language: Английский

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