13252-80-7

Upstream product

• 672-13-9 2-hydroxy-5-methoxybenzaldehyde 
• 81375-98-6 4,4-bis(ethylsulfanyl)but-3-en-2-one 
• 105-45-3 acetoacetic acid methyl ester 
• 141-97-9 ethyl acetoacetate 

Downstream Products

• 1620636-13-6 10-methoxy-1,5-dimethyl-3-phenylchromeno[4,3-d]pyrazolo[3,4-b]pyridin-6(3H)-one 
• 1448308-54-0 diethyl 1-(3-chlorophenyl)-3-(6-methoxy-2-oxo-2H-chromene-3-yl)-1H-pyrazole-4,5-dicarboxylate 
• 1448308-32-4 3-{1-[(E)-2-(3-chlorophenyl)hydrazono]ethyl}-6-methoxy-2H-chromen-2-one 
• 326913-94-4 6-methoxy-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one 
• 1273552-02-5 8-methoxy-3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one 

Relevant academic research and scientific papers

Synthesis and biological evaluation of novel thiazolyl-coumarin derivatives as potent histone deacetylase inhibitors with antifibrotic activity

New histone deacetylases (HDAC) inhibitors with low toxicity to non-cancerous cells, are a prevalent issue at present because these enzymes are actively involved in fibrotic diseases. We designed and synthesized a novel series of thiazolyl-coumarins, substituted at position 6 (R = H, Br, OCH3), linked to classic zinc binding groups, such as hydroxamic and carboxylic acid moieties and alternative zinc binding groups such as disulfide and catechol. Their in vitro inhibitory activities against HDACs were evaluated. Disulfide and hydroxamic acid derivatives were the most potent ones. Assays with neonatal rat cardiac fibroblasts demonstrated low cytotoxic effects for all compounds. Regarding the parameters associated to cardiac fibrosis development, the compounds showed antiproliferative effects, and triggered a strong decrease on the expression levels of both α-SMA and procollagen I. In conclusion, the new thiazolyl-coumarin derivatives inhibit HDAC activity and decrease profibrotic effects on cardiac fibroblasts.

Application of iron-based metal-organic frameworks in catalysis: Oxidant-promoted formation of coumarins using Fe3O(BPDC)3 as an efficient heterogeneous catalyst

An iron-based metal-organic framework, Fe3O(BPDC)3, was synthesized, and was characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, atomic absorption spectrophotometry (AAS), and nitrogen physisorption measurements. The Fe-MOF could be used as an efficient heterogeneous catalyst for the synthesis of coumarins from salicylaldehydes and activated methylene compounds in the presence of tert-butyl hydroperoxide as the oxidant under base-free conditions. The Fe3O(BPDC)3 was more catalytically active for the synthesis of coumarins than other MOFs such as Cu2(BDC)2(BPY), Cu3(BTC)2, Cu2(BDC)2(DABCO), Ni2(BDC)2(DABCO), and Fe3O(BDC)3. This Fe-MOF also offered significantly higher catalytic activity for the transformation than that of common metal salts such as FeCl3, Fe(NO3)3, FeSO4, CuCl2, CuCl, Cu(NO3)2, and Ni(NO3)2. The Fe3O(BPDC)3 catalyst could be recovered and reused several times without significant degradation in catalytic activity. To the best of our knowledge, the oxidant-promoted formation of coumarins under heterogeneous catalysis conditions was not previously mentioned in the literature.

Improvement of fluorescence characteristics of coumarins: Syntheses and fluorescence properties of 6-methoxycoumarin and benzocoumarin derivatives as novel fluorophores emitting in the longer wavelength region and their application to analytical reagents

To improve the fluorescence characteristics, especially emission wavelength, of coumarins, various 3-substituted-6-methoxycoumarin derivatives were synthesized, and then benzocoumarin derivatives were also synthesized in expectation of the shift to the longer wavelength region by the extension of the conjugated system. Their fluorescence properties were investigated spectrophotometrically in acetonitrile and evaluated from the viewpoint of the intramolecular charge transfer (ICT) between push- and pull-substituents in the ground and the excited states. Among them, benzocoumarin derivatives especially fluoresced in the longer wavelength around 540 nm with remarkably large Stokes shifts beyond 10000 cm-1. Using such fluorophores, some novel fluorescence derivatization reagents for carboxylic acids, alcohols, phenols, and amines were preliminarily prepared as an example, and their derivatized products were also found to fluoresce in the longer wavelength region with large Stokes shifts.

Biocatalytic domino reaction: Synthesis of 2H-1-benzopyran-2-one derivatives using alkaline protease from Bacillus licheniformis

A novel BLAP (alkaline protease from Bacillus licheniformis) catalyzed synthesis of 2H-1-benzopyran-2-one derivatives was achieved by domino Knoevenagel/intramolecular transesterification reaction. The control of enzymatic chemoselectivity between Knoevenagel/intramolecular transesterification and Knoevenagel/intramolecular hemiketalization could be realized by adjusting parameters including solvent, water content and temperature. The products were obtained in acceptable yields. This BLAP catalyzed selective domino reaction provided an alternative synthetic method for 2H-1-benzopyran-2-one derivatives.

Synthesis and in vitro antioxidant activity evaluation of 3-carboxycoumarin derivatives and qsar study of their dpph radical scavenging activity

The in vitro antioxidant activities of eight 3-carboxycoumarin derivatives were assayed by the quantitative 1,1-diphenyl-2-picrylhydrazil (DPPH) radical scavenging activity method. 3-Acetyl-6-hydroxy-2H-1-benzopyran-2-one (C1) and ethyl 6-hydroxy-2-oxo-2H-1-benzopyran-3-carboxylate (C2) presented the best radical-scavenging activity. A quantitative structure-activity relationship (QSAR) study was performed and correlated with the experimental DPPH scavenging data. We used structural, geometrical, topological and quantum-chemical descriptors selected with Genetic Algorithms in order to determine which of these parameters are responsible of the observed DPPH radical scavenging activity. We constructed a back propagation neural network with the hydrophilic factor (Hy) descriptor to generate an adequate architecture of neurons for the system description. The mathematical model showed a multiple determination coefficient of 0.9196 and a root mean squared error of 0.0851. Our results shows that the presence of hydroxyl groups on the ring structure of 3-carboxy-coumarins are correlated with the observed DPPH radical scavenging activity effects.

An efficient solid-phase green synthesis of chromen-2-one derivatives

An efficient route for the synthesis of chromen-2-one derivatives (3a-h) via Knoevenagel condensation under solid phase by the condensation of salicylaldehydes (1) with various ethyl acetate derivatives (2) is described. The reaction has been done under conventional method as well as under solid-phase method. The later method has been found to be much better in terms of time and yield. The structures of all the compounds were confirmed by spectral and analytical data.

Amino-grafted SBA-15 material as dual acid-base catalyst for the synthesis of coumarin derivatives

We report herein an experimental and theoretical study concerning the preparation of the coumarins (2) from 2-hydroxybenzaldehydes (3) and ethyl acetoacetate (4) promoted by amino-grafted SBA-15 materials. The reaction takes places by Knoevenagel condensation between reagents, in the absence of any solvent and under mild conditions, followed by a non catalytic lactonization step. Amino-grafted SBA-15 loaded with secondary amine groups, MAP/SBA-15, was found to be the most efficient and totally recyclable catalyst as compared with its analog containing tertiary amine groups, DEAP/SBA-15 (where MAP and DEA are methyl aminopropyl and diethyl aminopropyl groups, respectively). Our theoretical analysis confirms that the steric congestion and the absence of NH protons as the catalytic active sites are determining factors for the increasing of the activation barrier and, therefore, for the lower catalytic activity and reactivity to the formation of the coumarin. The computational study herein reported demonstrates that MAP/SBA-15, a traditional basic mesoporous silica having NH protons, shows a dual acid-base catalytic behavior when used in the synthesis of coumarins via Knoevenagel condensation. Otherwise, the substitution in 2-hydroxybenzaldehydes (3) at 5-position clearly influences the acceptor and acidity capacities of the CHO and the OH groups as experimentally and theoretically demonstrated.

An approach to the synthesis of 2-Acylchromeno[3,4- c ]pyrrol-4(2 H)-one derivatives via a sequential three-component reaction

An efficient synthesis of 2-acylchromeno[3,4-c]pyrrol-4(2H)-one derivatives by a three-component reaction of salicylaldehydes, β-keto esters, and p-toluenesulfonylmethyl isocyanide is reported. Georg Thieme Verlag Stuttgart, New York.

Preparation and synthetic use of polymer-supported acetoacetate reagent

Coumarin synthesis using polymer-supported acetoacetate reagent was carried out to produce various coumarin derivatives in excellent yield and purity with a facile work-up process. It was found that the polymer reagent could be recycled without any diminishment of the yield and purity. Georg Thieme Verlag Stuttgart.

Synthesis and anti-acetylcholinesterase activities of novel glycosyl coumarylthiazole derivatives

Eleven glycosyl coumarylthiazole derivatives are synthesized by cyclization and condensation of glycosyl thiourea with 3-bromoacetyl coumarins in ethanol. The reaction conditions are optimized and good yields of products (80%–95%) are obtained. The structures of all new products were confirmed by IR, 1H and 13C NMR, and by HRMS (electrospray ionization). The in vitro acetylcholinesterase (AChE) inhibitory activities of these new compounds are tested by Ellman’s method. Among them, N-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-4-(6-nitrocoumarinyl)-1,3-thiazole-2-amine showed the best activity with an in vitro AChE inhibitory rate of 58% and an IC50 value of 12 ± 0.38 μg/mL.