C3 Functionalization of Indolizines via HFIP-Promoted Friedel–Crafts Reactions with (Hetero)arylglyoxals

Jung, Euijin; Jeong, Yerin; Kim, Hye-Yeon; Kim, Ikyon

doi:10.1021/acsomega.3c00236

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…While Vilsmeier–Haack formylation of 12a delivered 19 in 71% yield, Mannich reaction of 12a with formaldehyde and morpholine gave 20 . Friedel–Crafts-type monoaddition of 12a to phenylglyoxal in the presence of HFIP led to 21 in 81% yield . Compound 12ad underwent Suzuki–Miyaura cross-coupling smoothly to afford 22 .…”

Section: Resultsmentioning

confidence: 99%

Regioselective Access to 1,2,4-Triazole-Fused N-Heterocycle, Pyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, via Double Dehydrative Cyclizations

Kim

2023

J. Org. Chem.

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A highly efficient and regioselective approach to a novel 1,2,4-triazole-fused N-heterocyclic scaffold, pyrrolo[1,2-a][1,2,4]triazolo[3,4-c]pyrazine, was established by base-promoted reaction of pyrrole-2-carbonitrile-derived substrate with acyl hydrazide where domino double ring closures comprised of enamine formation, attack on nitrile, and cyclodehydration enabled sequential construction of pyrazine and 1,2,4-triazole ring systems with formation of three C–N bonds.

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Section: Resultsmentioning

confidence: 99%

Regioselective Access to 1,2,4-Triazole-Fused N-Heterocycle, Pyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, via Double Dehydrative Cyclizations

Kim

2023

J. Org. Chem.

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“…To validate our hypothesis, the requisite starting material 1 (when LG is OH) was envisioned to be easily prepared via a Friedel–Crafts-type reaction between phenol and arylglyoxal [ 24 ]. Inspired by our recent success in achieving the hexafluoroisopropanol (HFIP)-mediated hydroxyalkylation of indolizine 3 to arylglyoxal to afford 4 ( Scheme 1 b) [ 25 ], we expected that a HFIP-promoted Friedel–Crafts-type reaction between phenol 5 and arylglyoxal would give rise to 7 , which could be converted to benzofuran 8 , having an indole at the C3 position upon exposure to indole and p -toluenesulfonic acid (PTSA) ( Scheme 1 c). The biological investigation of benzofuran–indole hybrid 8 [ 26 ] revealed that this class of compounds exhibit anticancer activity against PC9 and A549 lung cancer cells via the inhibition of phosphorylated EGFR.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Evaluation of Novel Benzofuran–Indole Hybrids as Epidermal Growth Factor Receptor Inhibitors against Non-Small-Cell Lung Cancer Cells

Lee,

Lee

et al. 2024

Pharmaceuticals

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The epidermal growth factor receptor (EGFR), also known as ErbB1 and HER1, belongs to the receptor tyrosine kinase family. EGFR serves as the primary driver in non-small-cell lung cancer (NSCLC) and is a promising therapeutic target for NSCLC. In this study, we synthesized a novel chemical library based on a benzofuran–indole hybrid scaffold and identified 8aa as a potent and selective EGFR inhibitor. Interestingly, 8aa not only showed selective anticancer effects against NSCLC cell lines, PC9, and A549, but it also showed significant inhibitory effects against the double mutant L858R/T790M EGFR, which frequently occurs in NSCLC. In addition, in PC9 and A549 cells, 8aa potently blocked the EGFR signaling pathway, cell viability, and cell migration. These findings suggest that 8aa, a benzofuran–indole hybrid derivative, is a novel EGFR inhibitor that may be a potential candidate for the treatment of NSCLC patients with EGFR mutations.

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Construction of Functionalized ortho‐Naphthoquinone Methides via Site‐Selective Ring Opening of 1‐Siloxy‐1,4‐epoxy‐1,4‐dihydronaphthalenes

Aijima,

Komagawa,

Akai

et al. 2023

Adv Synth Catal

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Abstract1‐Siloxy‐4‐(benzyloxy)methyl‐1,4‐epoxy‐1,4‐dihydronaphthalenes, generated from benzynes and furans, underwent automatic site‐selective ring opening because of the synergetic effect of the steric strain of the 1,4‐epoxy moiety and the electron‐donating ability of the siloxy group on the acetal structure to afford the precursors of ortho‐naphthoquinone methides (o‐NQMs). Subsequent Lewis acid‐facilitated o‐NQM formation and annulation with olefins afforded multi‐fused heterocycles. Notably, the consecutive hexacyclic skeleton of rubioncolin B was constructed via solvent‐dependent regioselective annulation of naphthofuran derivatives.

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C3 Functionalization of Indolizines via HFIP-Promoted Friedel–Crafts Reactions with (Hetero)arylglyoxals

Cited by 3 publications

References 23 publications

Regioselective Access to 1,2,4-Triazole-Fused N-Heterocycle, Pyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, via Double Dehydrative Cyclizations

Regioselective Access to 1,2,4-Triazole-Fused N-Heterocycle, Pyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, via Double Dehydrative Cyclizations

Anticancer Evaluation of Novel Benzofuran–Indole Hybrids as Epidermal Growth Factor Receptor Inhibitors against Non-Small-Cell Lung Cancer Cells

Construction of Functionalized ortho‐Naphthoquinone Methides via Site‐Selective Ring Opening of 1‐Siloxy‐1,4‐epoxy‐1,4‐dihydronaphthalenes

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