223519-90-2

Upstream product

• 455-19-6 4-Trifluoromethylbenzaldehyde 
• 118-93-4 o-hydroxyacetophenone 

Downstream Products

• 104197-22-0 4'-Trifluoromethylflavonol 
• 128814-90-4 2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one 
• 1362479-03-5 2-(4-(trifluoromethyl)phenyl)-2H-chromene 

Relevant academic research and scientific papers

Influence of a 4′-substituent on the efficiency of flavonol-based fluorescent indicators of β-glycosidase activity

This article presents novel fluorescent probes, based on the excited-state intramolecular proton transfer (ESIPT) phenomenon and flavonols, sensitive to the action of specific glycosidases. 4′-Substituted flavonols were synthesized, using various approaches, and glycosylated withd-glucose,N-acetyl-d-glucosamine andd-glucuronic acid. Evaluation of the β-glycosidase activities was performed in neutral and acidic pH. In all the cases examined, an acidic environment accelerated enzymatic hydrolysis. It was demonstrated that the 4′-chloroflavonyl glycosides of all sugars tested, both in neutral and acidic pH, are the ones most sensitive to the presence of hydrolase. In turn, 4′-dimethylaminoflavonyl glucoside is not sensitive to glucosidase action at all. Generally, the rate of enzymatic hydrolysis increases as the electron-withdrawing nature of the 4′-substituent increases. An exception is the trifluoromethyl group which, in spite of having the most favourable Hammett constant, does not contribute enough to increase the rate of hydrolysis of its glucoside. The presented experimental results are supported by the electrostatic potential (ESP) analysis and related to the mechanisms of glycoside bond enzymatic hydrolysis.

Substituent-Controlled Divergent Cascade Cycloaddition Reactions of Chalcones and Arylalkynols: Access to Spiroketals and Oxa-Bridged Fused Heterocycles

Herein, we report substituent-controlled divergent cascade cycloaddition reactions of chalcones and arylalkynols in the presence of PtI2. Depending on the substituent on the chalcone, either spiroketals or oxa-bridged fused heterocycles could be obtained in the ranges of 86–97% and 87–95% yields under identical reaction conditions. Control experiments were carried out to elucidate the origin of the high chemoselectivity. These provide a method for the synthesis of a diverse array of structurally complex oxygen-containing heterocycles. (Figure presented.).

Chapter Open for the Excited-State Intramolecular Thiol Proton Transfer in the Room-Temperature Solution

We report here, for the first time, the experimental observation on the excited-state intramolecular proton transfer (ESIPT) reaction of the thiol proton in room-temperature solution. This phenomenon is demonstrated by a derivative of 3-thiolflavone (3TF), namely, 2-(4-(diethylamino)phenyl)-3-mercapto-4H-chromen-4-one (3NTF), which possesses an - S - H···O= intramolecular H-bond (denoted by the dashed line) and has an S1 absorption at 383 nm. Upon photoexcitation, 3NTF exhibits a distinctly red emission maximized at 710 nm in cyclohexane with an anomalously large Stokes shift of 12 230 cm-1. Upon methylation on the thiol group, 3MeNTF, lacking the thiol proton, exhibits a normal Stokes-shifted emission at 472 nm. These, in combination with the computational approaches, lead to the conclusion of thiol-type ESIPT unambiguously. Further time-resolved study renders an unresolvable (180 fs) ESIPT rate for 3NTF, followed by a tautomer emission lifetime of 120 ps. In sharp contrast to 3NTF, both 3TF and 3-mercapto-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (3FTF) are non-emissive. Detailed computational approaches indicate that all studied thiols undergo thermally favorable ESIPT. However, once forming the proton-transferred tautomer, the lone-pair electrons on the sulfur atom brings non-negligible nπ? contribution to the S1′ state (prime indicates the proton-transferred tautomer), for which the relaxation is dominated by the non-radiative deactivation. For 3NTF, the extension of π-electron delocalization by the diethylamino electron-donating group endows the S1′ state primarily in the ππ? configuration, exhibiting the prominent tautomer emission. The results open a new chapter in the field of ESIPT, covering the non-canonical sulfur intramolecular H-bond and its associated ESIPT at ambient temperature.

Chiral Hydroxytetraphenylene-Boron Complex Catalyzed Asymmetric Diels-Alder Cycloaddition of 2′-Hydroxychalcones

(S)-2,15-Cl2-DHTP-boron complex catalyst for the asymmetric Diels-Alder cycloaddition of 2′-hydroxychalcones and dienes was developed and tested. The resulting cyclohexenes with three chiral centers were obtained in high yields (up to 98%) with excellent stereoselectivities (up to >20:1 endo/exo, >99% ee). This catalytic system features high efficiency, broad substrate scopes, and mild reaction conditions. In addition, a DFT study was performed to explain the stereochemical course of the asymmetric induction.

Exploration of synthetic antioxidant flavonoid analogs as acetylcholinesterase inhibitors: an approach towards finding their quantitative structure–activity relationship

The binding interactions between acetylcholinesterase (AChE) and a series of antioxidant flavonoid analogs were studied by fluorescence spectroscopic assay. The present study incorporated different classes of naturally occurring and synthetic flavonoid compounds like flavones, isoflavones, and chalcones as well as a few standard antioxidants. The AChE inhibitory (AChEI) activity of these compounds was further analyzed using in silico techniques, namely pharmacophore mapping, quantitative structure–activity relationship (QSAR) analysis, and molecular docking studies. We have also compared the AChE inhibitory and radical scavenging antioxidant activities of these compounds. Both the AChE inhibitory and antioxidant activities of these compounds were found to be highly dependent on their structural patterns. However, it was observed that, in general, flavones are comparatively better AChE inhibitors as well as antioxidants compared to chalcones. [Figure not available: see fulltext.].

Temperature-Controlled Stereodivergent Synthesis of 2,2′-Biflavanones Promoted by Samarium Diiodide

In this work, the first example of a radical stereodivergent reaction directed towards the stereoselective synthesis of both (R*,R*)- and (R*,S*)-2,2′-biflavanones promoted by samarium diiodide is reported. Control experiments showed that the selectivity of this reaction was exclusively controlled by the temperature. It was possible to generate a variety of 2,2′-biflavanones bearing different substitution patterns at the aromatic ring in good-to-quantitative yields, being both stereoisomers of the desired compounds obtained with total or high control of selectivity. A mechanism that explains both the generation of the corresponding 2,2′-biflavanones and the selectivity is also discussed. The structure and stereochemistry determination of each isomer was unequivocally elucidated by single-crystal X-ray diffraction experiments.

Synthesis of 3-HCF2S-Chromones through Tandem Oxa-Michael Addition and Oxidative Difluoromethylthiolation

A simple protocol for the synthesis of difluoromethylthiolated chromen-4-ones using elemental sulfur and ClCF2CO2Na as the difluoromethylthiolating agent is described. Three-component reactions of 2′-hydroxychalcones, ClCF2CO2Na, and sulfur under basic conditions using TEMPO as the oxidant afforded HCF2S-containing 4H-chromen-4-one and 9H-thieno[3,2-b]chromen-9-one derivatives in good yield. The protocol is practical and efficient, and the starting materials are cheap and readily available.

Inhibition of LPS-stimulated ROS production by fluorinated and hydroxylated chalcones in RAW 264.7 macrophages with structure-activity relationship study

Based on the importance of the previous fluorinated and/or hydroxylated chalcones studies, thirty-six compounds were designed as phenyl or hydroxyphenyl bearing fluoro, trifluoromethyl or trifluoromethoxy phenyl propenones and synthesized by applying modified Claisen-Schmidt condensation reaction as a single step. Inhibitory effects of the synthesized compounds on ROS production stimulated by LPS in RAW 264.7 macrophage were evaluated. Structure-activity relationship (SAR) study revealed that the compounds possessing para-hydroxyphenyl group combined with meta-fluoro or meta-trifluoromethyl phenyl group, and meta/para-hydroxyphenyl group combined with ortho-trifluoromethoxyphenyl group have an essential role in inhibiting the LPS-stimulated ROS production in RAW 264.7 macrophages. The most significant inhibitory effect on LPS-stimulated ROS production in RAW 264.7 macrophages was observed in compound 30 that possessed para-hydroxyphenyl group along with ortho-trifluoromethoxyphenyl group.

Pharmacophore model of the quercetin binding site of the SIRT6 protein

SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. We have previously reported on the identification of quercetin and vitexin as SIRT6 inhibitors,