Category: 328-90-5

He, Xuefeng published the artcileHighly efficient synthesis of benzodioxins with a 2-site quaternary carbon structure by secondary amine-catalyzed dual Michael cascade reactions, Name: 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Organic & Biomolecular Chemistry (2018), 16(30), 5533-5538, database is CAplus and MEDLINE.

Salicylic acids and substituted ynones were employed as substrates to afford a class of valuable 4H-benzo[d][1,3]dioxin-4-ones with a 2-site quaternary carbon structure in up to 92% yield by secondary amine-catalyzed dual Michael cascade reactions under mild reaction conditions. The α,β-unsaturated ketone as the key intermediate in the cascade process was successfully separated and characterized. As a result, a new reaction route for ynone species is demonstrated, which is totally different from the existing allenamine activation model.

Organic & Biomolecular Chemistry published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Name: 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Jiao, Shulin published the artcileThe synthesis of an antifungal 1,2,4-triazole drug and the establishment of a drug delivery system based on zeolitic imidazolate frameworks, Related Products of alcohols-buliding-blocks, the publication is New Journal of Chemistry (2019), 43(47), 18823-18831, database is CAplus.

Invasive fungal infections (IFIs) are deadly fungal infections with a high mortality rate, particularly in patients who have undergone prolonged use of chemotherapy drugs, transplant surgery and so on. Among them, Candida albicans has attracted great attention as an important pathogen. Triazoles such as voriconazole and fluconazole are considered to be some of the most effective and widely used antifungal drugs. However, the resistance of fungi to these drugs and the toxicity of triazoles to normal human cells are the main reasons for the difficulty of treating invasive fungal infections. In this paper, a novel trifluoromethyl-containing triazole compound, TPHMB, was designed and synthesized for the first time. The single crystal was obtained by the solution evaporation method, and its mol. structure was determined by a single crystal diffractometer. The activity against Candida albicans was detected (MIC₉₀ = 8μg ml^-1). In addition, for the first time, we used the metal organic framework ZIF-8 to establish an effective, low-toxicity and pH-responsive antifungal drug delivery system with less side effects via reducing the non-specific aggregation in normal tissues and improving water solubility Detailed material characterizations confirmed the successful encapsulation of TPHMB in the ZIF-8 matrix, which demonstrated good drug release at pH = 5; plate count was used to find the excellent synergy of ZIF-8 against Candida albicans. This study not only provides a reference for the development of new triazole drugs, but also helps develop an effective delivery system of such drugs in vivo to achieve an effective treatment of fungal infections.

New Journal of Chemistry published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Related Products of alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Montanaro, Sara published the artcilePhotonucleophilic Addition of the ε-Amino Group of Lysine to a Triflusal Metabolite as a Mechanistic Key to Photoallergy Mediated by the Parent Drug, Related Products of alcohols-buliding-blocks, the publication is ChemMedChem (2009), 4(7), 1196-1202, database is CAplus and MEDLINE.

A mechanism for triflusal-induced photoallergy involving complexation of 2-hydroxy-4-trifluoromethylbenzoic acid with site I of human serum albumin and subsequent formation of a covalent adduct by photoreaction between a metabolite and a neighboring lysine residue is proposed. This is supported by the observed photobinding to poly-L-lysine. Thereby, a photoantigen is generated, which is a likely trigger of the immune response. The goal of the work presented herein is to gain deeper insight into the mol. basis of photoallergy mediated by triflusal through its active metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). For this purpose, the interaction between HTB and human serum albumin (HSA) was investigated by fluorescence and laser flash photolysis to monitor inclusion into the protein binding sites through variation in the excited-state properties. A remarkable lengthening of HTB triplet lifetime in the presence of HSA was observed The use of oleic acid as a displacement probe clearly suggests the preference for dark binding in site I. The mechanism of photobinding was studied by irradiation of HTB in the presence of amino acids, and, in the case of lysine, a photoadduct was detected that arises from nucleophilic attack by the ε-amino group to the trifluoromethyl substituent of HTB. Accordingly, photobinding of the metabolite to poly-L-lysine was also observed Overall, these results are consistent with a mechanism for triflusal photoallergy involving complexation of HTB to site I of HSA and subsequent formation of a covalent photoadduct with one neighboring lysine residue.

ChemMedChem published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Related Products of alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Denton, Elliott H. published the artcileCatalytic Carbochlorocarbonylation of Unsaturated Hydrocarbons via C-COCl Bond Cleavage, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Angewandte Chemie, International Edition (2021), 60(43), 23435-23443, database is CAplus and MEDLINE.

A palladium-catalyzed difunctionalisation of unsaturated C-C bonds with acid chlorides was reported. Formally, C-COCl bond of an acid chloride was cleaved and added, with complete atom economy, across either strained alkenes or a tethered alkyne to generate new acid chlorides I [Ar = Ph, 2-naphthyl, benzo[b]thiophen-2-yl, etc.]. The transformation does not require exogenous carbon monoxide, operated under mild conditions, showed a good functional group tolerance, and gave isolated products with excellent stereoselectivity. The intermol. reaction tolerated both aryl- and alkenyl-substituted acid chlorides and was successful when carboxylic acids were transformed to acid chloride in situ. The reaction also showed an example of temperature-dependent stereodivergence which, together with plausible mechanistic pathways, was investigated by DFT calculations Moreover, it was shown that benzofurans could be formed in an intramol. variant of reaction. Finally, derivatisation of products from intermol. reaction provided a highly stereoselective approach for synthesis of tetrasubstituted cyclopentanes.

Angewandte Chemie, International Edition published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Park, Sung Min published the artcilePopulation pharmacokinetic and pharmacodynamic modeling of transformed binary effect data of triflusal in healthy Korean male volunteers: a randomized, open-label, multiple dose, crossover study, Computed Properties of 328-90-5, the publication is BMC Pharmacology and Toxicology (2014), 75/1-75/21, 21 pp., database is CAplus and MEDLINE.

Background Triflusal is a drug that inhibits platelet aggregation. In this study we investigated the dose-exposure- response relationship of a triflusal formulation by population pharmacokinetic (PK) and pharmacodynamic (PD) modeling of its main active metabolite, hydroxy-4-(trifluoromethyl) benzoic acid (HTB). Methods This study was a randomized, open-label, multiple-dose, two-period, two-treatment, comparative crossover design. All volunteers received a single oral loading dose of 900 mg of triflusal on Day 1, followed by a dose of 600 mg/day from Day 2 to 9. Using data from 34 healthy volunteers, 476 HTB plasma concentration data points and 340 platelet aggregation data points were used to construct PK and PD models resp. using NONMEM (version 6.2). As the PD endpoint was qual., we implemented binary anal. of ‘inhibition’ and ‘non-inhibition’ rather than using the actual value of the test. The final PK-PD model was evaluated using a visual predictive check (VPC) and bootstrap. Results The time-concentration profile of HTB over the entire dosing period was described by a one-compartment model with a first-order formation rate constant for HTB. Weight was selected as a covariate for clearance and volume of triflusal, resp. The structure and the population estimates for triflusal PK were as follows: oral clearance (CL/F) = 0.2 · (weight/71.65)0.845 L/h, oral volume of distribution (V/F) = 8.3 · (weight/71.65) L, and kf = 0.341 h-1. A sigmoid relationship between triflusal concentration and the probability of significant inhibition with shape factor was chosen as the final PD model. No time delay between concentration and response was identified. The final structure between predicted concentration (Cpred,ij γ) and the probability of inhibition of platelet aggregation (IPA) relationship was as follows: Probability of IPA = Cpred,ij19 / (84.9 μg/mL19 + Cpred,ij19). Thus, we concluded this relationship is more like quantal concentration-response relationship. The current dosing regimen was considered to be efficacious based on the EC50 estimate of 84.9 μg/mL obtained in this study. Conclusions A PK and binary probability PD model of triflusal was successfully developed for Korean healthy volunteers. The model may be used to further prediction inhibition of platelet aggregation by triflusal.

BMC Pharmacology and Toxicology published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Computed Properties of 328-90-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Kim, Seung-Woo published the artcileRobust neuroprotective effects of 2-((2-oxopropanoyl)oxy)-4-(trifluoromethyl)benzoic acid (OPTBA), a HTB/pyruvate ester, in the postischemic rat brain, Synthetic Route of 328-90-5, the publication is Scientific Reports (2016), 31843, database is CAplus and MEDLINE.

Postischemic brain damage in stroke is proceded with complicated pathol. events, and so multimodal drug treatments may offer better therapeutic means for improving clin. outcomes. Here, we report robust neuroprotective effects of a novel compound, 2-((2-oxopropanoyl)oxy)-4-(trifluoromethyl)benzoic acid (OPTBA), a 2-hydroxy-4-trifluoromethyl benzoic acid (HTB, a metabolite of triflusal)-pyruvate ester. I.v. administration of OPTBA (5 mg/kg) 3 or 6 h after middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats reduced infarct volumes to 38.5 ± 11.4% and 46.5 ± 15.3%, resp., of that of MCAO controls, and ameliorated motor impairment and neurol. deficits. Importantly, neuroprotective effects of OPTBA were far greater than those afforded by combined treatment of HTB and pyruvate. Furthermore, OPTBA suppressed microglial activation and proinflammatory cytokine inductions more effectively than HTB/pyruvate co-treatment in the postischemic brain and LPS-treated cortical slice cultures and also attenuated NMDA-induced neuronal death in hippocampal slice cultures. LC-MS anal. demonstrated that OPTBA was hydrolyzed to HTB and pyruvate with a t_1/2 of 38.6 min in blood and 7.2 and 2.4 h in cortex and striatum, resp., and HTB was maintained for more than 24 h both in blood and brain tissue. Together these results indicate OPTBA acts directly and via its hydrolysis products, thus acting as a multimodal neuroprotectant in the postischemic brain.

Scientific Reports published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Synthetic Route of 328-90-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Ohmura, Toshimichi published the artcileIridium-Catalyzed C(sp³)-H Addition of Methyl Ethers across Intramolecular Carbon-Carbon Double Bonds Giving 2,3-Dihydrobenzofurans, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Advanced Synthesis & Catalysis (2019), 361(19), 4448-4453, database is CAplus.

Intramol. addition of an O-Me C(sp³)-H bond across a carbon-carbon double bond occurs in the iridium-catalyzed reaction of Me 2-(propen-2-yl)phenyl ethers 2-MeC(=CH₂)-4-R-3-R¹-2-R²C₆HOMe (R = H, Me, Cl, t-Bu; R¹ = H, Me, MeO, CF₃; R² = H, Me, Ph, t-Bu, Br; R¹R² = CH=CH-CH=CH). The Ir/(S)-DTBM-SEGPHOS catalyst promotes the reaction efficiently in toluene at 110-135 °C to afford 3,3-dimethyl-2,3-dihydrobenzofurans I. Enantioselective C(sp³)-H addition is achieved in the reaction of Me 2-(1-siloxyethenyl)phenyl ethers 2-TBSOC(=CH₂)-4-R³-3-R⁴-2-R⁵C₆HOMe (R³ = H, Cl, t-Bu; R⁴ = H, MeO; R⁵ = H, Me, MeO, t-Bu, Cl; R⁴R⁵ = CH=CH-CH=CH), affording enantioenriched 3-hydroxy-2,3-dihydrobenzofuran derivatives II with up to 96% ee.

Advanced Synthesis & Catalysis published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Ohmura, Toshimichi published the artcileIridium-Catalyzed C(sp³)-H Addition of Methyl Ethers across Intramolecular Carbon-Carbon Double Bonds Giving 2,3-Dihydrobenzofurans, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Advanced Synthesis & Catalysis (2019), 361(19), 4448-4453, database is CAplus.

Intramol. addition of an O-Me C(sp³)-H bond across a carbon-carbon double bond occurs in the iridium-catalyzed reaction of Me 2-(propen-2-yl)phenyl ethers 2-MeC(=CH₂)-4-R-3-R¹-2-R²C₆HOMe (R = H, Me, Cl, t-Bu; R¹ = H, Me, MeO, CF₃; R² = H, Me, Ph, t-Bu, Br; R¹R² = CH=CH-CH=CH). The Ir/(S)-DTBM-SEGPHOS catalyst promotes the reaction efficiently in toluene at 110-135 °C to afford 3,3-dimethyl-2,3-dihydrobenzofurans I. Enantioselective C(sp³)-H addition is achieved in the reaction of Me 2-(1-siloxyethenyl)phenyl ethers 2-TBSOC(=CH₂)-4-R³-3-R⁴-2-R⁵C₆HOMe (R³ = H, Cl, t-Bu; R⁴ = H, MeO; R⁵ = H, Me, MeO, t-Bu, Cl; R⁴R⁵ = CH=CH-CH=CH), affording enantioenriched 3-hydroxy-2,3-dihydrobenzofuran derivatives II with up to 96% ee.

Advanced Synthesis & Catalysis published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Montanaro, Sara published the artcilePhotonucleophilic Addition of the ε-Amino Group of Lysine to a Triflusal Metabolite as a Mechanistic Key to Photoallergy Mediated by the Parent Drug, Related Products of alcohols-buliding-blocks, the publication is ChemMedChem (2009), 4(7), 1196-1202, database is CAplus and MEDLINE.

A mechanism for triflusal-induced photoallergy involving complexation of 2-hydroxy-4-trifluoromethylbenzoic acid with site I of human serum albumin and subsequent formation of a covalent adduct by photoreaction between a metabolite and a neighboring lysine residue is proposed. This is supported by the observed photobinding to poly-L-lysine. Thereby, a photoantigen is generated, which is a likely trigger of the immune response. The goal of the work presented herein is to gain deeper insight into the mol. basis of photoallergy mediated by triflusal through its active metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). For this purpose, the interaction between HTB and human serum albumin (HSA) was investigated by fluorescence and laser flash photolysis to monitor inclusion into the protein binding sites through variation in the excited-state properties. A remarkable lengthening of HTB triplet lifetime in the presence of HSA was observed The use of oleic acid as a displacement probe clearly suggests the preference for dark binding in site I. The mechanism of photobinding was studied by irradiation of HTB in the presence of amino acids, and, in the case of lysine, a photoadduct was detected that arises from nucleophilic attack by the ε-amino group to the trifluoromethyl substituent of HTB. Accordingly, photobinding of the metabolite to poly-L-lysine was also observed Overall, these results are consistent with a mechanism for triflusal photoallergy involving complexation of HTB to site I of HSA and subsequent formation of a covalent photoadduct with one neighboring lysine residue.

ChemMedChem published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Related Products of alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Denton, Elliott H. published the artcileCatalytic Carbochlorocarbonylation of Unsaturated Hydrocarbons via C-COCl Bond Cleavage, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Angewandte Chemie, International Edition (2021), 60(43), 23435-23443, database is CAplus and MEDLINE.

A palladium-catalyzed difunctionalisation of unsaturated C-C bonds with acid chlorides was reported. Formally, C-COCl bond of an acid chloride was cleaved and added, with complete atom economy, across either strained alkenes or a tethered alkyne to generate new acid chlorides I [Ar = Ph, 2-naphthyl, benzo[b]thiophen-2-yl, etc.]. The transformation does not require exogenous carbon monoxide, operated under mild conditions, showed a good functional group tolerance, and gave isolated products with excellent stereoselectivity. The intermol. reaction tolerated both aryl- and alkenyl-substituted acid chlorides and was successful when carboxylic acids were transformed to acid chloride in situ. The reaction also showed an example of temperature-dependent stereodivergence which, together with plausible mechanistic pathways, was investigated by DFT calculations Moreover, it was shown that benzofurans could be formed in an intramol. variant of reaction. Finally, derivatisation of products from intermol. reaction provided a highly stereoselective approach for synthesis of tetrasubstituted cyclopentanes.

Angewandte Chemie, International Edition published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts