First intramolecular Diels–Alder reactions using chromone derivatives: synthesis of chromeno[3,4-<i>b</i>]xanthones and 2-(benzo[<i>c</i>]chromenyl)chromones

Albuquerque, Hélio M. T.; Santos, Clementina M.M.; Cavaleiro, José A. S.; Silva, Artur M. S.

doi:10.1039/c7nj05185a

Cited by 14 publications

(6 citation statements)

References 22 publications

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“…( E )-5-methoxy-2-[2-(prop-2-yn-1-yloxy)styryl]-4 H -chromen-4-one (3c) : yield 361 mg (87%). Both spectroscopic and analytic data are in accordance with those previously published [ 34 ].…”

Section: Methodssupporting

confidence: 87%

Chromeno[3,4-b]xanthones as First-in-Class AChE and Aβ Aggregation Dual-Inhibitors

Malafaia

Oliveira

Fernandes

et al. 2021

IJMS

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Alzheimer’s disease (AD) is a complex multifactorial disorder, mainly characterized by the progressive loss of memory and cognitive, motor, and functional capacity. The absence of effective therapies available for AD alongside the consecutive failures in the central nervous system (CNS) drug development has been motivating the search for new disease-modifying therapeutic strategies for this disease. To address this issue, the multitarget directed ligands (MTDLs) are emerging as a therapeutic alternative to target the multiple AD-related factors. Following this concept, herein we describe the design, synthesis, and biological evaluation of a family of chromeno[3,4-b]xanthones as well as their (E)-2-[2-(propargyloxy)styryl]chromone precursors, as first-in-class acetylcholinesterase (AChE) and β-amyloid (Aβ) aggregation dual-inhibitors. Compounds 4b and 10 emerged as well-balanced dual-target inhibitors, with IC50 values of 3.9 and 2.9 μM for AChE and inhibitory percentages of 70 and 66% for Aβ aggregation, respectively. The molecular docking showed that most of the compounds bound to AChE through hydrogen bonds with residues of the catalytic triad and π-stacking interactions between the main scaffold and the aromatic residues present in the binding pocket. The interesting well-balanced activities of these compounds makes them interesting templates for the development of new multitarget compounds for AD.

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Section: Methodssupporting

confidence: 87%

Chromeno[3,4-b]xanthones as First-in-Class AChE and Aβ Aggregation Dual-Inhibitors

Malafaia

Oliveira

Fernandes

et al. 2021

IJMS

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“…The interest of our research group in MW-assisted DA reactions for the synthesis of heterocycles dates back to 2003. However, the intramolecular version of the DA reaction using 4 H -chromen-4-one derivatives was only reported 15 years later [ 55 ], with the synthesis of 2-(benzo[ c ]chromenyl)-4 H -chromen-4-ones 41 and chromeno[3,4- b ]-9 H -xanthen-9-ones 42 in 78–85% and 75–82% yield, respectively, through intramolecular DA reaction followed by chloranil-mediated aromatization of O -propargyl 4 H -chromen-4-ones with distinct unsaturated π-systems 39 and 40 ( Scheme 13 ) [ 55 ].…”

Section: Diels–alder Reactions Using 4 H -Chromen-4-ones and Quinolin-4(1 H )-Ones As Dienesmentioning

confidence: 99%

Microwave Irradiation: Alternative Heating Process for the Synthesis of Biologically Applicable Chromones, Quinolones, and Their Precursors

2021

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Microwave irradiation has become a popular heating technique in organic synthesis, mainly due to its short reaction times, solventless reactions, and, sometimes, higher yields. Additionally, microwave irradiation lowers energy consumption and, consequently, is ideal for optimization processes. Moreover, there is evidence that microwave irradiation can improve the regioselectivity and stereoselectivity aspects of vital importance in synthesizing bioactive compounds. These crucial features of microwave irradiation contribute to its inclusion in green chemistry procedures. Since 2003, the use of microwave-assisted organic synthesis has become common in our laboratory, making our group one of the first Portuguese research groups to implement this heating source in organic synthesis. Our achievements in the transformation of heterocyclic compounds, such as (E/Z)-3-styryl-4H-chromen-4-ones, (E)-3-(2-hydroxyphenyl)-4-styryl-1H-pyrazole, (E)-2-(4-arylbut-1-en-3-yn-1-yl)-4H-chromen-4-ones, or (E)-2-[2-(5-aryl-2-methyl-2H-1,2,3-triazol-4-yl)vinyl]-4H-chromen-4-ones, will be discussed in this review, highlighting the benefits of microwave irradiation use in organic synthesis.

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“…173 (E)-2′-Propargyloxy-2-styrylchromones (115) were used as substrates in a microwave-assisted intramolecular Diels-Alder reaction, affording chromeno [3,4-b]-xanthones 116 (Scheme 17B). 174 During optimization processes, besides the variation of solvent, Lewis acid, temperature, and reaction time, different oxidizing agents were also tested in order to push the reaction towards the oxidized product 116, without the formation of secondary products that are not fully oxidized. Optimal conditions for MAOS of chromeno [3,4-b]xanthones are the use of 1,2,4-trichlorobenzene (1,2,4-TCB) as a solvent, under MW irradiation at 200°C for 60 min and then the addition of the oxidizing agent chloranil to the reaction crude, under MW irradiation at 80°C for 30 min.…”

Section: Synthesis Of Xanthones From 2-substituted Chromonesmentioning

confidence: 99%

Recent advances in the synthesis of xanthones and azaxanthones

et al. 2020

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First intramolecular Diels–Alder reactions using chromone derivatives: synthesis of chromeno[3,4-b]xanthones and 2-(benzo[c]chromenyl)chromones

Cited by 14 publications

References 22 publications

Chromeno[3,4-b]xanthones as First-in-Class AChE and Aβ Aggregation Dual-Inhibitors

Chromeno[3,4-b]xanthones as First-in-Class AChE and Aβ Aggregation Dual-Inhibitors

Microwave Irradiation: Alternative Heating Process for the Synthesis of Biologically Applicable Chromones, Quinolones, and Their Precursors

Recent advances in the synthesis of xanthones and azaxanthones

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