Multicomponent Cascade Reaction of 3-Formylchromones: Highly Selective Synthesis of Functionalized 9-Azabicyclo[3.3.1]nonane Derivatives

Duan, Ying-Gang; Hu, Xing-Mei; Cao, Xin-Ling; Lv, Kai-Hong; Yan, Sheng‐Jiao

doi:10.1021/acs.orglett.1c02431

Cited by 32 publications

(17 citation statements)

References 45 publications

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“…Multicomponent reactions (MCRs) have emerged as a powerful tool for the purpose that a series of chemical processes can be controlled in a one-pot operation 17,18 . These reactions involve forming multiple bonds in a single conversion in a one-pot process without separating intermediates [19][20][21][22] .…”

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confidence: 99%

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Pourtaher

Hasaninejad

Iraji

2022

Sci Rep

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The objective of this study was to design new polysubstituted pyrrole derivatives as selective acetylcholinesterase (AChE) inhibitors to target Alzheimer's disease. In this context, a highly efficient, one-pot, sequential, multi-component synthesis of a diverse range of polysubstituted pyrroles was developed through a sequential domino strategy by the condensation of amines with 1,1-bis(methylthio)-2-nitroethene (BMTNE), Knovenagle reaction of arylglyoxals with malono derivatives and subsequent Michael addition and intramolecular cyclization reaction in EtOH at reflux. Thirty-nine synthesized compounds were evaluated as AChE and butyrylcholinesterase (BChE) inhibitors. Among the synthesized compounds, compound 4ad (IC50 = 2.95 ± 1.31 µM) was the most potent and selective AChE inhibitor with no significant inhibition against butyrylcholinesterase BChE. A kinetic study of 4ad revealed that this compound inhibited AChE in an uncompetitive mode. Based on a molecular modeling study, compound 4ad due to its small size properly fitted into the active site of AChE compared to BChE and stabilized by H-bond and hydrophobic interactions with the critical residues of the AChE binding pocket. Consequently, it was proposed that the 4ad derivative can be an ideal lead candidate against AD with a simple and practical operation of synthetic procedures.

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confidence: 99%

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Pourtaher

Hasaninejad

Iraji

2022

Sci Rep

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“…Known compounds were characterized by comparing their proton nuclear magnetic resonance ( 1 H NMR) spectra to the previously reported data. New compounds were characterized by 1 H NMR, carbon nuclear magnetic resonance ( 13 C NMR), and mass spectrometry (MS). Copies of 1 H NMR and 13 C NMR spectra have been included at the end of the Supporting Information.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Copies of 1 H NMR and 13 C NMR spectra have been included at the end of the Supporting Information. 1 H NMR spectra were recorded on Bruker 300 and 400 MHz instruments, and chemical shifts are reported in ppm (δ) relative to the internal standard tetramethylsilane (TMS, δ 0.00 ppm). 13 C NMR chemical shifts are reported in ppm with respect to solvent resonance as the internal standard (e.g., CDCl 3 at 77.0 ppm).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Trimethyl((1-phenylvinyl)oxy)silane (2a), 69 trimethyl((1-(ptolyl)vinyl)oxy)silane (2b), 69 ((1-(4-methoxyphenyl)vinyl)oxy)trimethylsilane (2c), 69 ((1-(benzo[d] [1,3]dioxol-5-yl)vinyl)oxy)trimethylsilane (2d), 69 ((1-(3-methoxyphenyl)vinyl)oxy)trimethylsilane (2e), 70 trimethyl((1-(4-(trifluoromethyl)phenyl)v i n y l ) o x y ) s i l a n e ( 2 f ) , 7 1 m e t h y l 3 -( 1 -((trimethylsilyl)oxy)vinyl)benzoate (2g), 72 4-(1-((trimethylsilyl)-oxy)vinyl)benzonitrile (2h), 71 trimethyl((1-(4-nitrophenyl)vinyl)oxy)silane (2i), 69 ((1-(4-fluorophenyl)vinyl)oxy)trimethylsilane (2j), 69 ((1-(4-chlorophenyl)vinyl)oxy)trimethylsilane (2k), 69 ((1-(4-bromophenyl)vinyl)oxy)trimethylsilane (2l), 69 ((1-(4iodophenyl)vinyl)oxy)trimethylsilane (2m), 69 ((1-(2-chlorophenyl)vinyl)oxy)trimethylsilane (2n), 73 trimethyl((1-(naphthalen-1-yl)vinyl)oxy)silane (2o), 69 trimethyl((4-phenylbuta-1,3-dien-2-yl)oxy)silane (2p), 74 trimethyl((4-(p-tolyl)buta-1,3-dien-2-yl)oxy)silane (2q), 74 trimethyl((1-(1-methylcyclopropyl)vinyl)oxy)silane (2r), 75 ((3,3-dimethylbut-1-en-2-yl)oxy)trimethylsilane (2s), 76 (cyclopent-1-en-1-yloxy)trimethylsilane (2t), 7 7 and ethyl 2-oxo-3-((trimethylsilyl)oxy)but-3-enoate (2u). 78 The following carbodiimides were prepared as per the literature protocols.…”

Section: ■ Experimental Proceduresmentioning

confidence: 99%

“…The reaction was carried out according to the general method using diisopropylcarbodiimide (1a, 100 mg, 0.79 mmol, 1 equiv) and ( (1-(benzo[d] [1,3]dioxol-5-yl)vinyl)oxy)trimethylsilane (2d, 240.7 mg, 1.02 mmol, 1.3 equiv). The crude product was purified by flash column chromatography using silica gel and a gradient of EtOAc and petroleum ether (ratio = 60:40) to afford the title product as a white solid (174.0 mg, 76%).…”

Section: -(Benzo[d][13]dioxol-5-yl)-33-bis(isopropylamino)prop-2-en-1...mentioning

confidence: 99%

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Synthetic Access to α-Oxoketene Aminals by the Nucleophilic Addition of Enol Silane-Derived Palladium(II) Enolates to Carbodiimides

et al. 2022

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Synthetically important α-oxoketene aminal intermediates can now be accessed from readily available and inexpensive carbodiimides as starting materials via the nucleophilic addition of palladium enolates derived from enol silane precursors. This operationally simple method features mild reaction conditions, including open air atmosphere, ligand-free metal catalysis, broad substrate scope, and multi-gram scalability. Select synthetic applications that take advantage of the enamine character of α-oxoketene aminals and involve C-nucleophilic additions to electrophilic systems, including an α,β-unsaturated ester, an azo dicarboxylate, an aralkyl halide, and an aldehyde, are demonstrated.

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Synthesis of Functionalized 3‐(1H‐Isochromen)‐chromones via Ag₂O‐Catalyzed Cascade Cyclization Reaction of o‐Hydroxyarylenaminones with o‐Alkynylbenzaldehydes

et al. 2022

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A silver-catalyzed protocol for the synthesis of 3-(1H-isochromen)-chromones is described. The method involves an initial 6-endo-dig cyclization of o-alkynylbenzaldehydes and domino CÀ H alkylation and chromone annulation of the ohydroxyarylenaminones, which enables the installation of 1H-isochromen and chromone in a single structure. This synthetic strategy is advantageous for the excellent regioselectivity, step economy, concise one-pot methodology, gram-scale synthesis, as well as high bond-forming efficiency.

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Multicomponent Cascade Reaction of 3-Formylchromones: Highly Selective Synthesis of Functionalized 9-Azabicyclo[3.3.1]nonane Derivatives

Cited by 32 publications

References 45 publications

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Synthetic Access to α-Oxoketene Aminals by the Nucleophilic Addition of Enol Silane-Derived Palladium(II) Enolates to Carbodiimides

Synthesis of Functionalized 3‐(1H‐Isochromen)‐chromones via Ag₂O‐Catalyzed Cascade Cyclization Reaction of o‐Hydroxyarylenaminones with o‐Alkynylbenzaldehydes

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Multicomponent Cascade Reaction of 3-Formylchromones: Highly Selective Synthesis of Functionalized 9-Azabicyclo[3.3.1]nonane Derivatives

Cited by 32 publications

References 45 publications

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Synthetic Access to α-Oxoketene Aminals by the Nucleophilic Addition of Enol Silane-Derived Palladium(II) Enolates to Carbodiimides

Synthesis of Functionalized 3‐(1H‐Isochromen)‐chromones via Ag2O‐Catalyzed Cascade Cyclization Reaction of o‐Hydroxyarylenaminones with o‐Alkynylbenzaldehydes

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Synthesis of Functionalized 3‐(1H‐Isochromen)‐chromones via Ag₂O‐Catalyzed Cascade Cyclization Reaction of o‐Hydroxyarylenaminones with o‐Alkynylbenzaldehydes