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Usage

Uses

Used in Pharmaceutical Industry:
4-hydroxy[1,1'-biphenyl]-3-carboxylic acid is used as a starting material for the synthesis of biologically active compounds due to its unique chemical structure and functional groups. Its hydroxyl and carboxylic acid groups can be modified to create new molecules with potential therapeutic effects.
Used in Chemical Industry:
In the chemical industry, 4-hydroxy[1,1'-biphenyl]-3-carboxylic acid is used as a building block for the production of dyes and pigments. Its aromatic structure and functional groups make it a versatile component in the synthesis of various colorants.
Used in Food Science and Nutrition:
4-hydroxy[1,1'-biphenyl]-3-carboxylic acid is used for its antioxidant properties in the field of food science and nutrition. Its ability to neutralize free radicals and protect against oxidative stress can contribute to the development of healthier food products and supplements.
Despite the potential applications of 4-hydroxy[1,1'-biphenyl]-3-carboxylic acid, further research is necessary to fully understand its properties and explore additional uses in various industries.

Upstream product

• 92-69-3 4-Phenylphenol 
• 15719-64-9 methylammonium carbonate 
• 107410-07-1 2-methoxy-5-phenylbenzoic acid 
• 89-55-4 5-bromosalicyclic acid 
• 98-80-6 phenylboronic acid 
• 124-38-9 carbon dioxide 
• 100-58-3 phenylmagnesium bromide 
• 31044-59-4 diethyl phenylboronate 
• 143-66-8 sodium tetraphenyl borate 
• 119-30-2 2-hydroxy-5-iodobenzoic acid 
• 17504-13-1 methyl 4-hydroxy-[1,1’-biphenyl]-3-carboxylate 
• 4068-75-1 methyl 5-iodosalicylate 
• 17504-10-8 methyl 4-methoxy-[1,1'-biphenyl]-3-carboxylate 
• 40757-09-3 methyl 2-methoxy-5-iodobenzoate 

Downstream Products

• 92-69-3 4-Phenylphenol 
• 67127-10-0 4-hydroxy-biphenyl-3-carboxylic acid 1⁽²⁾H-tetrazol-5-ylamide 
• 4906-68-7 3-bromo-5-phenylsalicylic acid 
• 1855-23-8 5-cyclohexyl-2-hydroxybenzoic acid 
• 17504-13-1 methyl 4-hydroxy-[1,1’-biphenyl]-3-carboxylate 
• 17784-39-3 4-hydroxy-biphenyl-3-carboxylic acid phenyl ester 

Relevant academic research and scientific papers

Synthesis of the tricyclic core structure of vindoline

An efficient synthesis of the core tricyclic structure (18) of vindoline has been achieved using the strategy, which features an intramolecular 1,3-dipolar cycloaddition of the azido dienone (12) to give aziridine (13) with complete region- and stereocontrol.

Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway

In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, α-amino-β-carboxymuconate-?-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+). In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (ACMSD) for further metabolism and energy production. Therefore, the inhibition of ACMSD increases NAD+ levels. In this study, an Food and Drug Administration (FDA)-approved drug, diflunisal, was found to competitively inhibit ACMSD. The complex structure of ACMSD with diflunisal revealed a previously unknown ligand-binding mode and was consistent with the results of inhibition assays, as well as a structure-activity relationship (SAR) study. Moreover, two synthesized diflunisal derivatives showed half-maximal inhibitory concentration (IC50) values 1 order of magnitude better than diflunisal at 1.32 ± 0.07 μM (22) and 3.10 ± 0.11 μM (20), respectively. The results suggest that diflunisal derivatives have the potential to modulate NAD+ levels. The ligand-binding mode revealed here provides a new direction for developing inhibitors of ACMSD.

Bi-aryl analogues of salicylic acids: Design, synthesis and sar study to ameliorate endoplasmic reticulum stress

Introduction: Endoplasmic reticulum (ER) stress condition is characterized as the accu-mulation of misfolded or unfolded proteins in lumen of ER. This condition has been implicated in various diseases and pathologies including β-cell apoptosis, Alzheimer’s disease and atherosclerosis. We have reported that hydroxynaphthoic acids (HNA), naphtha-lene analogues of salicylic acid (SA), reduced ER stress. In this study, we explored structural modification to bi-aryl analogues of SA. Methods: Palladium-catalyzed cross-coupling was applied to synthesize bi-aryl analogues of SA. Anti-ER stress activity was monitored by using our cell-based assay system where ER stress is induced by tunicamycin. To monitor ER stress markers, ER stress was induced physiologically relevant palmitate system. Results: Many analogues decreased ER stress signal induced by tunicamycin. Compounds creating dihedral angle between Ar group and SA moiety generally increased the activity but gave some cytotoxicity to indicate the crucial role of flat conformation of aromatic region. The best compound (16e) showed up to almost 6-fold and 90-fold better activity than 3-HNA and tauro-ursodeoxycholic acid, positive controls, respectively. ER stress markers such as p-PERK and p-JNK were accordingly decreased in Western blotting upon treatment of 16e under palmitate-induced condition. Conclusion: Anti-ER stress activity and toxicity profile of bi-aryl analogues of SA could provide a novel platform for potential therapy for protein misfolding diseases.

Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl2 nanocatalyst

A green synthesis of variously substituted biphenyl carboxylic acids was achieved through Suzuki–Miyaura cross-coupling of a bromobenzoic acid with an aryl boronic acid using a water-soluble fullerene-supported PdCl2 nanocatalyst (C60-TEGs/ PdCl2). Yields of more than 90% were obtained at room temperature in 4 h using 0.05 mol% catalyst and 2 equiv. K2CO3.

Synthesis of zwitterionic palladium complexes and their application as catalysts in cross-coupling reactions of aryl, heteroaryl and benzyl bromides with organoboron reagents in neat water

N-(3-Chloro-2-quinoxalinyl)-N′-arylimidazolium salts (aryl = 2,6-diisopropylphenyl [HL1Cl]Cl, aryl = mesityl [HL2Cl]Cl) have been synthesized by treating 2,3-dichloroquinoxaline with the corresponding N′-arylimidazole in neat water. Facile reactions of these imidazolium salts with Pd(PPh3)4 and Pd2(dba)3/PPh3 (dba = dibenzyledene acetone) at 50 °C have afforded zwitterionic palladium(ii) complexes [Pd(HL1)(PPh3)Cl2] (I) and [Pd(HL2)(PPh3)Cl2] (II) in excellent yields. I and II have been tested for their ability to catalyze Suzuki-Miyaura cross coupling (SMC) reactions in neat water/K2CO3 and are found to be highly active for carrying out these reactions between aryl bromides and organoboron reagents. Furthermore, the scope of the catalyst I was also examined by employing (hetero)aryl bromides, hydrophilic aryl bromides, benzyl bromides and various organoboron reagents. More than 80 aryl/benzyl bromide-arylboronic acid combinations were screened in neat water/K2CO3 and it was found that I was a versatile catalyst, which produced biaryls/diarylmethanes in excellent yields. A TON of 82 000 was achieved by using I. Studies on the mechanism have also been carried out to investigate the involvement of carbene complexes in the catalytic path. Poison tests and a two-phase test were also conducted and the results are reported.

Synthesis, structure elucidation, DNA-PK and PI3K and anti-cancer activity of 8- and 6-aryl-substituted-1-3-benzoxazines

The synthesis of 6-aryl, 8- aryl, and 8-aryl-6-chloro-2-morpholino-1,3-benzoxazines with potent activity against PI3K and DNA-PK is described. Synthesis of thirty one analogues was facilitated by an improved synthesis of 3-bromo-2-hydroxybenzoic acid 13 by de-sulphonation of 3-bromo-2-hydroxy-5-sulfobenzoic acid 12 en route to 2-methylthio-substituted-benzoxazine intermediates 17-19. From this series, compound 20k (LTURM34) (dibenzo[b,d]thiophen-4-yl) (IC50 = 0.034 μM) was identified as a specific DNA-PK inhibitor, 170 fold more selective for DNA-PK activity compared to PI3K activity. Other compounds of the series show markedly altered selectivity for various PI3K isoforms including compound 20i (8-(naphthalen-1-yl) a potent and quite selective PI3Kδ inhibitor (IC50 = 0.64 μM). Finally, nine compounds were evaluated and showed antiproliferative activity against an NCI panel of cancer cell lines. Compound 20i (8-(naphthalen-1-yl) showed strong anti-proliferative activity against A498 renal cancer cells that warrants further investigation.

A versatile approach for the synthesis of para -substituted arenes via palladium-catalyzed C-H functionalization and protodecarboxylation of benzoic acids

While a great number of ortho C-H functionalization reactions have been developed and several breakthroughs have been achieved in meta C-H activation, para C-H functionalization is still in its infancy stage. In this article, a versatile strategy for the synthesis of para-substituted arenes has been developed via a tandem process consisting of palladium-catalyzed C-H functionalization and subsequent copper-catalyzed protodecarboxylation of benzoic acids. Both electron-withdrawing and electron-donating functionalities can be introduced into the para positions of arenes bearing a variety of substituents.

General method for the synthesis of salicylic acids from phenols through palladium-catalyzed silanol-directed C-H carboxylation

A silanol-directed, palladium-catalyzed C-H carboxylation reaction of phenols to give salicylic acids has been developed. This method features high efficiency and selectivity, and excellent functional-group tolerance. The generality of this method was demonstrated by the carboxylation of estrone and by the synthesis of an unsymmetrically o,o′-disubstituted phenolic compound through two sequential C-H functionalization processes.

Tuning transthyretin amyloidosis inhibition properties of iododiflunisal by combinatorial engineering of the nonsalicylic ring substitutions

Two series of iododiflunisal and diflunisal analogues have been obtained by using a two step sequential reaction solution-phase parallel synthesis. The synthesis combined an aqueous Suzuki-Miyaura cross-coupling and a mild electrophilic aromatic iodination step using a new polymer-supported iodonium version of Barluengas reagent. From a selected set of 77 noniodinated and 77 iodinated diflunisal analogues, a subset of good transthyretin amyloid inhibitors has been obtained with improved turbidimetry inhibition constants, high binding affinity to transthyretin, and good selectivity for TTR compared to other thyroxine binding proteins.

Urea-based porous organic frameworks: Effective supports for catalysis in neat water

Two urea-based porous organic frameworks, UOF-1 and UOF-2, were synthesized through a urea-forming condensation of 1,3,5-benzenetriisocyanate with 1,4-diaminobenzene and benzidine, respectively. UOF-1 and UOF-2 possess good hydrophilic properties and high scavenging ability for palladium. Their palladium polymers, PdII/UOF-1 and PdII/UOF-2, exhibit high catalytic activity and selectivity for Suzuki-Miyaura cross-coupling reactions and selective reduction of nitroarenes in water. The catalytic reactions can be efficiently performed at room temperature. Palladium nanoparticles with narrow size distribution were formed after the catalytic reaction and were well dispersed in UOF-1 and UOF-2. XPS analysis confirmed the coordination of the urea oxygen atom with palladium. SEM and TEM images showed that the original network morphology of UOF-1 and UOF-2 was maintained after palladium loading and catalytic reactions. Feeling supportive? Two urea-based porous organic frameworks were prepared by a facile urea-forming condensation and can serve as effective supports in palladium-catalyzed Suzuki-Miyaura cross-coupling reactions and reduction of nitroarenes in water. The reactions can even be efficiently performed at room temperature. The original morphology of the urea-based frameworks was maintained after the catalytic reactions.