Hydroxyl Derivatives Research Articles

The Green Synthesis of 6-amino-5-cyano-4-phenyl-2-Hydroxy and Mercapto Pyrimidine Derivatives

The simple, quick, green and efficient method for the synthesis of 6-amino-5-cyano-4-phenyl-2-mercapto pyrimidine and its hydroxyl derivatives using CdFe2(C4H4O6)35H2O. This new procedure is much more efficient, apart from its simplicity; the important advantage of the present procedure is the ability to tolerate variation in all the three components reactions. To the best of our knowledge, this is one of the quickest, economical, and simple alternatives towards the synthesis of 6-amino-5-cyano-4-phenyl-2-mercapto pyrimidine. Ease of separation of pure product, selectively and in high yields in comparison to the two-step strategies, are a few of the unique features of this method.

N,N'-(2-aryl-2-oxoethane-1,1-diyl)diamides as convenient synthons for the preparation of 3-amido-2-arylbenzofurans

The general method for the synthesis of 2-arylbenzofuran containing amides was elaborated. The considered approach is based on interaction of various phenols with N,N'-(2-aryl-2-oxoethane-1,1-diyl)diamides, which can be obtained from arylglyoxals and primary amides. The employment of formic acid as a solvent is necessary condition for the presented protocol. The undoubted advantage of the developed method is the possibility of using a wide range of aromatic hydroxyl derivatives. The dignity of this synthesis is readily accessible starting materials, mild reaction conditions, atom economy and easy workup procedure, which can avoid chromatographic purification. The structure of one of the target benzofurans was established by X-ray diffraction.

Epoxidation of unsaturated fatty acid ester promoted by imidazolium acidic ionic liquids: An unexpected selectivity phenomena

AbstractEpoxidation of linseed oil fatty acid ethyl esters promoted by a series of functionalized imidazolium ionic liquids was studied. In this reaction acidic imidazolium ILs behave not only as an acid catalysts but also play an additional role as a specific activator for the reaction of epoxidation of unsaturated fatty derivatives in H2O2/formic acid oxidation system. The obtained results indicate that the hydrogen‐bonding interaction of imidazolium cation with epoxide group influences the selectivity of the epoxidation reaction. In particular, the presence of unprotected weak “acid” C2‐H proton significantly lowers the selectivity to hydroxyl derivatives. The obtained results also point to another example of specific polyfunctionality of ILs, especially imidazolium one, used as surfactants and process activators.

Computational studies on thermo-kinetics aspects of pyrolysis of isopropyl acetate and its methyl, bromide and hydroxyl derivatives

The gas-phase decomposition kinetics of isopropyl acetate (IPA) and its methyl, bromide and hydroxyl derivatives into the corresponding acid and propene were investigated using density functional theory (DFT) with the ωB97XD and M06–2x functionals, as well as the benchmark CBS-QB3 composite method. Transition state theory (TST) and RRKM theory calculations of rate constants under atmospheric pressure and in the fall-off regime were used to supplement the measured energy profiles. The results show that the formation of propene and bromoacetic acid is the most dominant pathway at the CBS-QB3 composite method, both kinetically and thermodynamically. There was a good agreement with experimental results. Pressures greater than 0.01 bar, corresponding to larger barrier heights are insufficient to ensure saturation of the measured rate coefficient when compared to the RRKM kinetic rates.Natural bond orbitals (NBO) charges, bond orders, bond indices, and synchronicity parameters all point to the considered pathways taking place via a homogenous, first-order concerted, as well as an asynchronous mechanism involving a non-planar cyclic six-membered transition state. The calculated data exhibit that the elongation of the Cα−O bond length and subsequent polarization of the Cα+δ…O−δ bond is the rate-determining step of the considered reactions in the cyclic transition state, which appears to be involved in this type of reaction.

Dietary supplementation with Aloe vera induces hepatic steatosis and oxidative stress together with a disruption of cellular signaling pathways and lipid metabolism related genes' expression in gilthead sea bream (Sparus aurata)

This study aimed to assess the effects of dietary increasing concentrations of Aloe vera (AV) powder of 0.5%, 2.5% and 5% on the growth performance, hepatic oxidative status, histology, and lipid metabolism and cellular signaling pathways-related genes' expression in gilthead sea bream (Sparus aurata). The preliminary phytochemical analysis revealed the richness of the dried AV extract on total phenol content, total flavonoid content, and condensed tannins when compared to the lyophilized sample. The dried extract showed a good DPPH-radical scavenging activity and its profiling by HPLC-DAD-ESI-MS revealed the presence of anthraquinones namely aloin A, aloin B and their hydroxyl (7-hydroxyaloin A and 7-hydroxyaloin B) and methyl-hydroxy (8-O-methyl-7-hydroxyaloin A and 8-O-methyl-7-hydroxyaloin B) derivatives as well as aloeresin A and B. The AV supplementation in fish diet did not affect growth performance (WG, WGR, and SGR) and feed utilization (FI, FCR, FER), and HSI indexes. However, the hepatic insulin-like growth factors (IGF-I and II) levels were significantly enhanced. Genes' expression levels of enzymes or transcription factors involved in lipolysis (lpl, hsl, and atgl), beta-oxidation (pparα, hadh), fatty acid transporters (cd36, fabp11) and lxrα were significantly down-regulated by the two high concentrations of AV powder. In contrast, fatty acid synthase (fas), a key gene of lipogenesis was significantly up regulated by dietary AV 5% powder supplementation. The induction of fas together with the down-regulation of peroxisome proliferator-activated receptor (pparα) and hydroxyacyl-coenzyme A dehydrogenase (hadh) could explain the lipid accumulation resulting in hepatic steatosis, which was confirmed by histological analysis, since the diets at the two higher concentrations (AV 2.5% and AV 5%) induced a significant increase in the number and diameter of hepatic lipid vacuoles in a dose dependent manner. Moreover, the mRNA levels of protein kinase B named (akt), mammalian target of rapamycin (mtor) and extracellular regulated kinase (erk1/2) involved in cell survival and proliferation were decreased by all AV powder supplemented diets. AV 5% increased catalase and glutathione S transferase activities suggesting a cellular strategy to fight against reactive oxygen species (ROS) accumulation. In conclusion, dietary supplementation with AV 0.5% is recommended for gilthead sea bream feed formulation, as it stimulates the igf-i expression. However, higher levels of AV should be avoided as they might cause lipid metabolism disruption, oxidative stress and liver steatosis.

Individual and combined degradation of N-heterocyclic compounds under sulfate radical-based advanced oxidation processes

Although the inhibitory effect of purines and phenols on the degradation of N-heterocyclic compounds under UV/peroxymonosulfate (PMS) has been reported, the understanding of contaminants' underlying mechanisms and kinetics is still very limited. In this study, five omnipresent nitrogenous bases (adenine, guanine, cytosine, thymine, and uracil) in the aquatic environment were used to study the inhibitory effect of N-heterocyclic compounds under UV/PMS by quantum chemical calculations. We found that HO• and SO4•− initiate base degradation with second-order rate constants of (0.11 – 15.6) × 109 M−1 s−1 and (7.25 – 13.5) × 109 M−1 s−1, respectively, and the primary products contain hydroxyl derivatives (HO-P), intermediate radicals (P(-H)•) and cationic radicals (P•+, only for purines). Because of the lower oxidation potentials of HO-P than their parent compounds (P), we first proposed a self-inhibition pathway in which HO-P can revert P(-H)• and P•+ back to P through H atom abstraction and single electron transfer reactions, respectively. A more significant self-inhibition was found in the degradation of uracil than that of adenine under UV/PMS because the former has a higher yield of hydroxylated derivatives. The main hydroxylated product (6-HO-U) of uracil repairs the uracil radical (U(-4H)•) at the reaction rate constants of 1.01 × 109 M−1 s−1. The combined degradation of bases showed that the reduction rate constants of purine cationic radicals have a linear relationship with the oxidation potentials of reductants. In the adenine-uracil mixture system, adenine inhibits uracil degradation by repairing U(-4H)• (2.33 × 105 M−1 s−1). This work revealed the mechanisms and kinetics of self-inhibition and joint-degradation of N-heterocyclic compounds, which is of great significance for understanding the collective removal of contaminants in the real water environment.

Design and Synthesis of α-Anomeric Diacetylene-Containing Glycosides as Photopolymerizable Molecular Gelators.

Glycolipids with diacetylene functional groups are fascinating compounds with many practical uses. Among these, diacetylene-containing gelators are especially important because they can form photopolymerizable gels, which are useful stimuli-responsive materials. Inspired by the unique properties of diacetylene-containing gelators and to understand the structural influences especially the location of the diacetylene functional groups on the self-assembling properties, a series of 15 novel N-acetyl-d-glucosamine derivatives with the diacetylene functional group introduced at the anomeric position were designed and synthesized. The diacetylene function is attached to the sugar through α-glycosylation with the distance from the anomeric oxygen being varied from one, two, and three methylene groups, and the other side contains hydroxyl, carboxyl, phenyl, and alkyl substituents. Remarkably, all compounds can form self-assembled gels in one or more selected solvents. A majority of these synthesized diacetylene glycosides are effective gelators for ethanol/water (v/v 1:1), dimethyl sulfoxide/water (v/v 1:1), and toluene, and one compound also formed a hydrogel at 1.0 wt %. Typically, these glycosides form gels that are photopolymerizable to afford red-colored gels. Scanning electronic microscopy indicated that the gelators formed helices, fibers, and planar sheet-like morphologies. The chemical structures of the derivatives affected their gelation properties and responses to UV treatment. The carboxylic acid-functionalized derivative 17 was able to immobilize basic solutions and form transparent gels. We expect that these diacetylene glycosides especially the hydroxyl and carboxylic acid derivatives will be useful as stimuli-responsive glycolipids for biomedical research.

Rational design, synthesis and activities of hydroxylated chalcones as highly potent dual functional agents against Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the extracellular amyloid plaques in the brain. Recent studies have shown that ferroptosis, a recently identified cell death pathway associated with the accumulation of lipid hydroperoxides, is closely related to the occurrence and exacerbation of AD. The application of ferroptosis inhibitors can alleviate the development of AD in both cellular and animal models. Herein, a series of dual-functional hydroxylated chalcone derivatives by integrating the heterocyclic dimethylaminopyrimidine in the core structure were designed and synthesized beyond our previous research to optimize their inhibition activities towards Aβ protein aggregation and ferroptosis simultaneously. The inhibitory ability of the novel synthesized chalcone derivatives were greatly improved. The results indicated that the introduction of the dimethylaminopyrimidine structure provided improved effect on Aβ protein aggregation inhibitory activity in both solution and cellular models. Trihydroxy chalcone derivative A-N-5 provided the best inhibition activities against Aβ protein aggregation in cellular models. The trihydroxy compound A-N-5 did not show cytotoxicity at the concentration lower than 100 µM (with IC50 > 1 mM), but had a significant effect on promoting cell proliferation. Results indicated that compound A-N-5 could potentially promote neuronal cell growth in the damaged brain tissue. The compound could also inhibit ferroptosis induced by RSL or erastin and reduce the lipid peroxidation levels induced by Aβ1-42 protein aggregation. Molecular docking was also conducted to explain the better inhibitory effect of novel compounds to inhibit Aβ protein aggregation compared to the previous designed molecules without incorporation of the dimethylaminopyrimidine. In summary, the trihydroxy compound A-N-5 showed the best inhibition activities against Aβ aggregation as well as ferroptosis with low cytotoxicity as a promising molecular skeleton candidate for further development of lead compound for in vivo test to treat AD.

Synthesis, Biological Evaluation, and Molecular Docking Study of 3-Amino and 3-Hydroxy-seco A Derivatives of α-Amyrin and 3-Epilupeol as Inhibitors of COX-2 Activity and NF-kB Activation.

In this study, a series of novel 3-seco-A derivatives of the natural triterpenes α-amyrin (1) and 3-epilupeol (2) were synthesized by a one-pot radical scission-oxidation procedure and evaluated in vitro and in vivo for their capacity to inhibit the inflammatory process. For the in vitro studies, the trans-4-hydroxy-l-proline methyl ester derivatives (1f and 2f) were consistently effective in inhibiting NO, IL-6, and TNF-α secretion, as well as inhibition of NF-κB activation, in RAW cells stimulated by LPS. The further in vivo anti-inflammatory study revealed that the trans-4-hydroxy-l-proline methyl ester derivatives (1f and 2f), together with 1g, were the most effective in inhibiting TPA-induced edema. Interestingly, the α-amyrin derivatives were the most potent inhibitors of COX-2, but inhibited COX-1 only to some extent. The hydroxyl derivative (1c) was selective for COX-2 inhibition (66.3 ± 1.1% at 17.5 μM) without affecting the COX-1 isoform and did not present toxicity. Molecular docking studies revealed that these compounds bind with their polar region in the cavity over Arg-120, and their lipophilic part is orientated to the HEM cofactor similarly to the natural substrate arachidonic acid in the catalytic site of COX-2. These results indicated that seco-A ursane derivatives could be considered promising candidates for the future development of selective NF-κB and COX-2 inhibitors.

Comparing the effect of benzoic acid and cinnamic acid hydroxyl derivatives on polyphenol oxidase: activity, action mechanism, and molecular docking.

Polyphenol oxidase (PPO) is considered to have a key role in the food industry because it initiates enzymatic browning in the processing and storage of fruit and vegetables. Increasing numbers of benzoic and cinnamic acid derivatives have been found to be efficient inhibitors of polyphenol oxidase, but a comparison study on activity and action mechanism is lacking. In this study, 18 benzoic acid and cinnamic acid hydroxy derivatives were selected and investigated. Three substrates, four activators and 11 inhibitors were identified from benzoic and cinnamic acid derivatives. 2,4-Dihydroxycinnamic acid and benzoic acid showed the strongest inhibitory effect on PPO, with IC50 of 0.092 and1.425 mmol L-1 , respectively. Benzoic acid reversibly inhibited PPO in a competitive manner, while 2,4-dihydroxycinnamic acid showed a mixed-type inhibition. Both of them showed that static-type fluorescence quenching and electrostatic interaction were the main driving force in the bonding process. Compared with benzoic acid, 2,4-dihydroxycinnamic acid more easily formed hydrogen bonds in the active site of PPO, making the interaction more stable. Comparative analysis showed that the inhibition effect of cinnamic acid hydroxyl derivatives on PPO was stronger than that of benzoic acid derivatives. Benzoic acid and 2,4-dihydroxycinnamic acid were the strongest inhibitors. PPO inhibitors identified from benzoic and cinnamic acid derivatives are expected to be promising inhibitors for controlling fruit and vegetable browning. © 2021 Society of Chemical Industry.

Pharmacological Investigation of Fluoro, Iodo and Hydroxy Derivative of Chloro Substituted Homoisoflavonoids

In present study, the synthesized substituted homoisoflavonoid derivatives were screened for their in vivo/in vitro antiarthritic activity, in vitro anti-inflammatory and DPPH free radical scavenging activity. The male Wistar rats were used for investigation of in vivo antiarthritic activity against complete freund’s adjuvant (CFA) induced arthritis and assessment was done for change in paw volume, serum marker enzymes (ALP, SGOT and SGPT) and membrane stabilization potential. in vitro anti-inflammatory activity was assessed by the protein denaturation method. In vitro free radical scavenging activity was assessed by the DPPH method. The result indicated that compound HIFa showed a significant antiarthritic activity as compared to other substituted homoisoflavonoid derivatives. The significant membrane stabilization and inhibition of protein denaturation showed in vitro antiarthritic and antiinflammatory activity of substituted homoisoflavonoid derivatives. The substituted homoisoflavonoid derivatives showed dose dependent DPPH free radical scavenging activity. From the present study, it was observed that the iodo derivative of substituted homoisoflavonoid derivatives have significant pharmacological activities as compared to floro and hydroxyl derivatives.

Electrochemical Behavior of Chloroquin, Azithromycin and Hydroxychloroquin onto Carbon-Clay Paste Electrode Doped with Titanium Oxide (TiO<sub>2</sub>)

The aim of this work is to prepare and characterize a carbon-clay paste electrode doped with Titanium Oxide (CPEA/TiO₂). This electrode is used to study the electrochemical behavior of drugs such as Chloroquin, Azithromycin and Hydroxychloroquin. The morphological, structural and functional characteristics of this electrode were carried out using X-ray diffraction (XRD), selected area electron diffraction (SAED), scanning electron microscopy (SEM), Fourrier transform infrared spectroscopy (FTIR). The electrochemical characterization was made by Cyclic Voltammetry (CV) in the potential range [-0.1V; 0.9V], in a phosphate buffer solution (0.1M; pH = 6.4); focused on the detection of an inorganic complex (ion [Fe(CN)₆]^3- (1mM)). The application was made focused on the detection of organic macromolecules such as azithromycin (AZI), chloroquin (CHL) and hydroxychloroquin (HYC). CPEA/TiO₂ was then subjected to electroanalysis in the same concentrations of the combinations AZI+CHL and AZI+HYC. However, in the presence of analyte the phenomena are irreversible with a dominance of oxidation phenomena. The electroactivity of the drugs used initially concerns the hydroxyl groups, observed around 0.050V (oxidation potential of the hydroxyl function in an intermediate form) and 0.560V (oxidation potential of the intermediate and in the carbonyl group). Secondly, the electro activity of the tertiary amine is highlighted by the potential value of 0.690V (attributable to the oxidation of the tertiary amine into an ammonium hydroxyl derivative). Current densities are more pronounced, which suggests a new molecule with significant electro activity. The oxidation mechanism is proposed. The electroactivity of the excipients (Lactose and Starch) used in these drugs is not negligible and evolves when going from one drug to two. However, the excipients are less noticeable in the AZI+HYC combination than in AZI+CHL.

Hypolignification: A Decisive Factor in the Development of Hyperhydricity.

One of the characteristics of hyperhydric plants is the reduction of cell wall lignification (hypolignification), but how this is related to the observed abnormalities of hyperhydricity (HH), is still unclear. Lignin is hydrophobic, and we speculate that a reduction in lignin levels leads to more capillary action of the cell wall and consequently to more water in the apoplast. p-coumaric acid is the hydroxyl derivative of cinnamic acid and a precursor for lignin and flavonoids in higher plant. In the present study, we examined the role of lignin in the development of HH in Arabidopsis thaliana by checking the wild-types (Ler and Col-0) and mutants affected in phenylpropanoid biosynthesis, in the gene coding for cinnamate 4-hydroxylase, C4H (ref3-1 and ref3-3). Exogenously applied p-coumaric acid decreased the symptoms of HH in both wild-type and less-lignin mutants. Moreover, the results revealed that exogenously applied p-coumaric acid inhibited root growth and increased the total lignin content in both wild-type and less-lignin mutants. These effects appeared to diminish the symptoms of HH and suggest an important role for lignin in HH.

Design and synthesis of naphthylchalcones as novel anti-leukaemia agents

A series of new hydroxylated chalcone derivatives with different substitution patterns on a phenyl ring A and B, were prepared by Claisen–Schmidt condensation in an aqueous alkaline base. The antiproliferative activity of the studied compounds was evaluated against the human leukaemia cell line U-937. The structure–activity relationship of these naphthylchalcones was investigated by the introduction of one methoxy or two methyl groups on the A ring, the introduction of a methoxy group on the naphthyl ring or by varying the position of the methoxy group on the A ring. The results revealed that the naphthylchalcone containing a methoxy group in position 6́ of the A ring was the most cytotoxic compound, with an IC50 value of 4.7 ± 0.5 μM against U-937 cells. This synthetic chalcone induced S and G2-M cell cycle arrest, a time-dependent increase in sub-G1 ratio and annexin-V positive cells, caspase activation and poly(ADP-ribose) polymerase cleavage. Apoptosis induction was blocked by a pan-caspase inhibitor and by the selective caspase-3/7 inhibitor and attenuated by the inhibition of c-jun N-terminal kinases / stress-activated protein kinases (JNK/SAPK) and phosphoinositide 3-kinase. The structure–activity relationship of naphthylchalcones against human leukaemia cells reveals that the major determining in cytotoxicity is the presence of a methoxy group in position 6́ of the A ring that suggest the potential of this compound or derivatives in the development of new anti-leukaemia drugs.

Lido-OH, a Hydroxyl Derivative of Lidocaine, Produced a Similar Local Anesthesia Profile as Lidocaine With Reduced Systemic Toxicities.

Background: lidocaine is one of the most commonly used local anesthetics for the treatment of pain and arrhythmia. However, it could cause systemic toxicities when plasma concentration is raised. To reduce lidocaine’s toxicity, we designed a hydroxyl derivative of lidocaine (lido-OH), and its local anesthesia effects and systemic toxicity in vivo were quantitively investigated.Method: the effectiveness for lido-OH was studied using mouse tail nerve block, rat dorsal subcutaneous infiltration, and rat sciatic nerve block models. The systemic toxicities for lido-OH were evaluated with altered state of consciousness (ASC), arrhythmia, and death in mice. Lidocaine and saline were used as positive and negative control, respectively. The dose-effect relationships were analyzed.Results: the half effective-concentration for lido-OH were 2.1 mg/ml with 95% confident interval (CI95) 1.6–3.1 (lidocaine: 3.1 mg/ml with CI95 2.6–4.3) in tail nerve block, 8.2 mg/ml with CI95 8.0–9.4 (lidocaine: 6.9 mg/ml, CI95 6.8–7.1) in sciatic nerve block, and 5.9 mg/ml with CI95 5.8–6.0 (lidocaine: 3.1 mg/ml, CI95 2.4–4.0) in dorsal subcutaneous anesthesia, respectively. The magnitude and duration of lido-OH were similar with lidocaine. The half effective doses (ED50) of lido-OH for ACS was 45.4 mg/kg with CI95 41.6–48.3 (lidocaine: 3.1 mg/kg, CI95 1.9–2.9), for arrhythmia was 16.0 mg/kg with CI95 15.4–16.8 (lidocaine: 3.0 mg/kg, CI95 2.7–3.3), and for death was 99.4 mg/kg with CI95 75.7–124.1 (lidocaine: 23.1 mg/kg, CI95 22.8–23.4). The therapeutic index for lido-OH and lidocaine were 35.5 and 5.6, respectively.Conclusion: compared with lidocaine, lido-OH produced local anesthesia at similar potency and efficacy, but with significantly reduced systemic toxicities.

Synthesis of New Antibiotics Derivatives by the Photocatalytic Method: A Screening Research

The aim of our study was to assess the possibility of using the photocatalytic process conducted in the presence of TiO2 to obtain new stable derivatives of antibacterial drugs. The possibility of introducing hydroxyl, chlorine, or bromide groups into antibiotics molecules was investigated. The experiments were conducted in aqueous solutions in the presence of TiO2-P25 as a photocatalyst, Cl− and Br− ions, and antibiotics belonging to eight different chemical classes. All experiments were initiated by UVa radiation. The kinetics of photocatalytic reactions and their quantum yield were determined, and the stable products were identified. All of the antibiotics used in the experiments underwent a photocatalytic transformation, and the quantum yields were in the range from 0.63 to 22.3%. The presence of Br− or FeCl3 significantly increased the efficiency of the photocatalytic process performed in the presence of TiO2, although Br− ion also acted as an inhibitor. Potentially biologically active chlorine derivatives from Trimethoprim, Metronidazole, Chloramphenicol, and bromine derivatives from Trimethoprim, Amoxicillin were obtained under experimental conditions. The potentially inactive halogen derivatives of Sulfamethoxazole and hydroxyl derivatives described in the literature were also identified.

Discovery of Dolastatinol: A Synthetic Analog of Dolastatin 10 and Low Nanomolar Inhibitor of Tubulin Polymerization.

We developed a highly potent anticancer agent, dolastatinol, which is a methylene hydroxyl derivative of dolastatin 10. Dolastatinol is a synthetic analog of dolastatin 10, synthesized by a solid-phase peptide Fmoc chemistry protocol on 2-chlorotrityl chloride resin utilizing a pH-triggering self-immolative monosuccinate linker. The introduction of the C-terminus hydroxyl methylene functionality preserves the anticancer properties of the parent dolastatin 10, including strong suppression of the cell proliferation, migration, high cytotoxicity. Our research establishes a new facile route toward the further development of C-terminus-modified dolastatin-10-based microtubule inhibitors for anticancer treatment.

Synthesis of 1,8‐Cineole Derivatives from 3‐Carene

AbstractWith the purpose of developing high‐value utilization approach for 3‐carene, various 1,8‐cineole derivatives bearing Br, OH, and NH2 groups at C‐6 were synthesized starting from it, following a new method of synthesis. The structure of 1,8‐cineole was established from the structure of carene by first introducing an OH and then carrying out ring‐opening and nucleophilic substitution reactions under acidic conditions. Br was simultaneously introduced at C‐6 as an active reaction site. The acidity of the medium significantly influenced the efficiency of the reaction. It was observed that trimethylsilyl bromide was the ideal reagent to carry out the reaction. 6‐Bromo‐1,8‐cineole was prepared from 3‐carene via a two‐steps process at 20 °C. The reaction time was ≤3 h. The maximum extent of conversion was 98.58 % and a selectivity of 60.66 % was achieved. Then, we synthesized two other compounds with high reactivities from 6‐bromo‐1,8‐cineole. 6‐Hydroxyl‐1,8‐cineole was synthesized by reacting 6‐bromo‐1,8‐cineole with H2O at 65 °C for 1 h. The extent of conversion was 98.49 % and the selectivity was 87.86 %. A hydroxyl derivative with >90 % purity was obtained after removing the solvent. 6‐Amino‐1,8‐cineole together with 6‐hydroxyl‐1,8‐cineole were synthesized by reacting 6‐bromo‐1,8‐cineole with ammonia with the conversion was >98 % under 70 °C for 1 h. Lower feed ratio of ammonia to 6‐bromo‐1,8‐cineole was good for the yield of amino derivative. The hydroxyl/amino ratio decreased from 4.0 to 1.6 with the feed ratio decreased from 8 to 4. The hydroxyl derivative and amino derivative could be efficiently separated by adjusting the pH of the reaction medium to obtain an amino derivative (>93 % purity).

Pyridine Scaffolds, Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives

Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.

An effect of positional isomerism of benzoic acid derivatives on antibacterial activity against Escherichia coli.

This study demonstrated the effect of positional isomerism of benzoic acid derivatives against E. coli ATCC 700728 with the serotype O157. The addition of hydroxyl and methoxyl substituents weakened the effect of acids against E. coli with respect to benzoic acid (except 2-hydroxybenzoic). The connection of the hydroxyl group at the second carbon atom in the benzoic ring reduced the time needed to kill bacterial cells. Phenolic acids with methoxyl substitutes limited the biofilm formation by E. coli to a greater extent than hydroxyl derivatives. The most significant influence on the antibacterial activity of phenolic acids has the type of substituent attached to the benzoic ring, their number, and finally the number of carbon atoms at which the functional group is located.