Letters in Organic Chemistry - Volume 15, Issue 9, 2018

The synthesis of a novel class of trichloro-1-{(N-arylamino)ethylidene}malononitrile via a copper-catalyzed multicomponent reaction of malononitrile-trichloroacetonitrile adduct and aryl halides in good yields is described. The reported protocol has some advantages such as simple and mild procedure, easy work-up, no column chromatography, available starting materials-catalyst, pure products and good to high yields.

Diverse pathways and inflammatory responses are controlled by cAMP which is a vital intracellular second messenger. The cAMP is suppressed by the enzyme Phosphodiesterase4 (PDE4) specifically PDE4B2, which is the target proteins articulated in the inflammatory cells, for instance, T cells and monocytes in the pathogenesis of diseases such as asthma, rheumatoid arthritis, COPD and multiple sclerosis. PDE4 inhibition leads to the enhancement of cAMP level, resulting in the downregulation of these diseases. In this investigation, docking analysis, ADMETox and drug-likeness have been conducted for the analysis of protein lead interaction and to check whether ventilago isolates can behave as potential ligands with pharmacological activity as PDE4 inhibitors. From this study, it has been established that 1RO6 and 1RO9 proteins have more stability than the other proteins. 34 Ventilago phytoconstituent isolates with five different organic nucleuses such as isofuranonaphthoquinones, anthraquinones, benzisochromanquinones, naphthalene, and naphthoquinones are used for the analysis. The in-silico studies displayed considerable binding affinity of ventilago isolates with the protein and accordingly, the ventilago isolates having anthraquinones nuclei like Calyculatone, 4,5-dihydroxynordigitoleutein and 2-hydroxyislandicin and the phytoconstituents containing naphthaquinones nucleus Cordeauxione possess the highest PDE4 inhibitory activity as they gave a strong hydrogen bonding profile with the amino acid residues of the target protein. The computational study provides evidence that the ventilago isolates can be used as valuable ligands with comparable PDE4 inhibitory activity as that of the standard drug Apremilast and further in vitro and in vivo investigations may prove its therapeutic potential.

Nano-Fe3O4@ZrO2-SO3H (n-FZSA), was utilized as a magnetic catalyst for the synthesis of various fluoroquinolone compounds. These compounds were prepared by the direct amination of 7- halo-6-fluoroquinolone-3-carboxylic acids with piperazine derivatives and (4aR,7aR)-octahydro-1Hpyrrolo[ 3,4-b] pyridine in water. The results showed that n-FZSA exhibited high catalytic activity towards the synthesis of fluoroquinolone derivatives, giving the desired products in high yields. Furthermore, the catalyst was recyclable and could be used at least seven times without any discernible loss in its catalytic activity. Overall, this new catalytic method for the synthesis of fluoroquinolone derivatives provides rapid access to the desired compounds in refluxing water following a simple work-up procedure, and avoids the use of organic solvents.

A facile and convenient approach for the synthesis of dimeric calixarene, with a C6-bridge is described. C6-bridge spacer molecule increased the synthetic dimmer ability for further macromolecular studies. Our results (experimental and computational) show that the dimeric calixarene 6 has good affinity for Inositol hexaphosphate IP6.

A novel and green heterogeneous nanocomposite, polyethylene oxide sulfonic acid coated on magnetic nanoparticles surface (Fe3O4@PEO-SO3H), was successfully synthesized and completely characterized by Fourier-transforms infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), vibrating sample magnetometry (VSM), inductively-coupled plasma (ICP), Brunauer– Emmett-Teller (BET), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses. Then, its catalytic activity was investigated in a one-pot four-component synthesis of polyhydroquinolines (PHQs). The present work includes various advantages such as high-to-excellent yields, short reaction times and availability of the substrates, reusability of the catalyst, operational simplicity and environmentally-benign conditions.

Background: Gliclazide is a second generation sulfonyl urea which acts as hypoglycemic agent (oral antidiabetic agent). It improves the function of blood coagulation, has hypoglycemic effect, and thus has been widely used in clinical treatment. Several syntheses of Gliclazide have been reported, but all of them have some drawbacks. Therefore, there has been an ever-increasing interest in finding a novel route for Gliclazide using simple and easily commercial available chemicals. Methods: A Novel and facile process of preparing Gliclazide is herein reported which is comprised of three steps. Aryl haloformate was reacted with amino heterocyclic compound to give carbamate. The salt of p-toluene sulfonamide was prepared with metal hydroxide or metal alkoxide, and this salt of sulfonamide was then reacted with carbamate to give Gliclazide. Results: The carbamate produced from aryl haloformates was reacted with salt of p-toluene sulfonamide in the presence of base to produce Gliclazide with good yield and purity. The salt of p-toluene sulfonamide was prepared by two methods. In one method, salt was prepared using base at 100°C in polar aprotic solvent which was reacted with carbamate at 25°C to give Gliclazide. This method gives 70% yield of Gliclazide with purity above 99%. In another method, the salt of p-toluene sulfonamide was prepared at 100°C in polar aprotic solvent using base. The salt was isolated. The isolated salt of sulfonamide is stable at 25°C. This salt was reacted with carbamate at 25°C to give Gliclazide. This method gives 64% yield of Gliclazide with purity above 99%. The various solvents, bases were tested in this investigation. It was observed that excellent yield of the product was obtained when the reaction was carried out by using DMSO as solvent and potassium tert-butoxide as base. Conclusion: In conclusion, we have developed new and effective process for the synthesis of Gliclazide via condensation of sulfonamide with various carbamates using a less expensive aryl haloformates with good yield and purity.

A series of protected and unprotected 3-O and 2, 3-di-O-alkyl derivatives of L-ascorbic acid were synthesized and their cytotoxic activity against metastatic breast epithelial carcinoma (MCF-7) cell line was evaluated. Cytotoxic activity evaluation indicated that compounds show moderate cytotoxic effects on tested cell line. Some of the 2, 3-di-O-alkyl derivatives of L-ascorbic acid exhibited potent inhibiting activity against MCF-7 cell line at micromolar concentrations. 2,3-di-O-4-chlorobenzyl- L-ascorbic acid exhibited 4 fold more cytotoxic activity (IC50 = 34.09 μM ) against MCF-7 cell line than L-ascorbic acid. 2, 3-di-O-alkyl derivatives exhibited more inhibition against MCF-7 cell line as compared to the 3-O-alkyl derivatives of L-Ascorbic acid.

Three-component reaction between arylglyoxal monohydrates, isocyanides and 1,3- diketones in water is reported. This reaction provides a simple and efficient route for the synthesis of poly-functionalized furan derivatives. The reaction conditions and work-up procedure are simple and products were obtained in good yields.

Immobilization of polyethylene glycol substituted 1-methylimidazolium bromide on the surface of Fe3O4 magnetic nanoparticles led to the synthesis of powerful and recyclable heterogeneous phase-transfer catalysts which were successfully used for the one-pot three-component condensation of aryl aldehydes, malononitrile and 1,3-dicarbonyl compounds, to afford the corresponding 2-amino-3- cyano-4H-pyrans. The catalysts can be readily recovered by simple magnetic decantation, and they can be reused several times with no considerable loss in their activity.

Background: Anthracnose, caused by the fungus Colletotrichum lindemuthianum, is one of the most important diseases that affect common beans. As some chalcones and triazoles are active cores against fungi, 1,2,3-triazolyl-chalcone hybrids could present more intense antifungal activities than the fungicides commercially available. Objective: The present work aimed at synthesizing these hybrids, evaluating them as antifungal agents against C. lindemuthianum, and identifying the enzymatic target of the most active substances using in silico calculations. Method: 1,2,3-triazole aldehydes and acetophenones underwent Claisen-Schmidt reactions to afford four known and six new hybrids, which were identified by spectrometric techniques. In vitro antifungal activities of these compounds against C. lindemuthianum were determined by MIC method. The most active compounds also underwent an assay with common bean plants inoculated with this fungus. An in silico study comprising pharmacophoric search and molecular docking was carried out with the most active substances. Results: Most of the compounds exhibited good to reasonable in vitro activity, and four of them displayed higher activity than the commercial fungicide methyl thiophanate. Among six 1,2,3-triazolylchalcones with the lowest MIC values, three of them reduced the anthracnose severity in common beans plants to levels similar to those observed for plants treated with methyl thiophanate. According to the in silico studies, these substances act against C. lindemuthianum through inhibition of the serine/ threonine-protein kinase and fatty acid synthase. Conclusion: 1,2,3-triazolyl-chalcone hybrids are very active against C. lindemuthianum. Apparently, they are able to inhibit two different enzymes produced by the fungus.

A model compound of graphene, with nine condensed aromatic rings has been optimized at DFT/B3LYP/6-311G+(d,p) level of theor, and the D index for aromaticity was calculated. The D index of eight possible epoxidation products was calculated showing that probably the reaction occurred only in the external crown of the molecule.

A very simple and efficient procedure for the preparation of primary amides is described from carboxylic acids using Mukaiyama reagent/KNCO in aqueous acetonitrile. Availability of the reagents, simplicity, and easy workup of the reaction crude make this method attractive for organic chemists.

In this study, the efficiency of some electrophilic halogen reagents including 2,4,6-trichloro- 1,3,5-triazine, 2,4,4,6-tetrabromo-2,5-cyclohexadienone, 2-chloro-1-methylpyridinium iodide, Nbromosuccinimide, trichloroisocyanuric acid, and 1,3-dibromo-5,5-dimethylhydantoin for the direct phosphine-free conversion of carboxylic acids into the corresponding acyl isothiocyanates was investigated. All of the reagents work well for this transformation, but, the best results were obtained when cyanuric chloride in the presence of pyridine was used at room temperature.

A wide variety of hydroxyaryl ketones bearing different motifs was successfully synthesized with good yields and excellent selectivities in the presence of HF@SiO2 as an environmental friendly acid under solvent-free condition. Mild and green reaction conditions and excellent yields (50-91%) make this method an attractive method for the efficient synthesis of hydroxyaryl ketones. Fries rearrangement of phenyl benzoate in the presence of HF@SiO2 led to p-hydroxybenzophenone, while phenyl acetate in the same conditions produced o-hydroxyacetophenone as a single isomer.