Letters in Organic Chemistry - Volume 16, Issue 2, 2019

Neglected tropical diseases (NTDs) affect more than a billion people worldwide, mainly populations living in poverty conditions. More than 56% of annual NTD deaths are caused by Leishmaniasis, Sleeping sickness, and Chagas disease. For these three diseases, many problems have been observed with the chemotherapeutic drugs commonly used, these being mainly resistance, high toxicity, and low efficacy. In the search for alternative treatments, hybridization is an interesting approach, which generates new molecules by merging two pharmacophores and then looking for improvements in biological activity or reduced compound toxicity. Here, we review various studies that present such hybrid molecules with promising in vitro and in vivo activities against Leishmania and Trypanosoma parasites.

In the present study, two novel chalcone glycosides, trans-3-ethoxy-4-O-(glucopyranoside) -2', 3', 4', 5', 6' -pentahydroxy chalcone (compound 1) and trans-3-methoxy-4-O-(glucopyranoside) -2', 3', 4', 5', 6' -pentahydroxy chalcone (compound 2) have been isolated from the leaves of Viburnum lantana L. The structures were elucidated by using 1H-NMR, 13C-NMR, 2D-NMR such as HMQC, HMBC and NOE experiments and UV-Vis, MS and IR spectra. The antioxidant property of hydroalcoholic extract was evaluated by DPPH style. The results revealed that the leave extract possesses significant antioxidant activity (IC50 = 52 μg/mL). This study indicates that hydroalcoholic extract of the leaves from this species is an important source of chalcone and flavonoid derivatives, as well as of useful natural antioxidants. These chalcone glycoside compounds were isolated for the first time from V. lantana leaves.

The synthesis of a variety of 2-aminobenzimidazoles via a one pot reaction of ophenylenediamine and trichloroacetonitrile catalyzed by copper (II) acetate in THF at room temperature, with good yields is described. Use of simple and readily available starting materials, good to high yields, free ligand, and no column chromatography are important features of this protocol.

An ordinary procedure for the synthesis of several 1, 4, 5-trisubstituted-1H-imidazole- 2(3H)-ones and -thiones by a one-pot three-component reaction of glacial acetic acid under solvent, microwave irradiation condition is proposed. The products were formed through cyclization of benzoin with isothiocyanates or isocyanates and ammonium acetate. All incorporated combinations were determined for their spectral and microanalytical information. These compounds were subsequently studied for their fluorescence properties.

Cu-catalyzed thiolation or selenylation of aryl C-H bonds with diaryl disulfides and diphenyl diselenides was accomplished using a readily removable directing group. This protocol represents a convenient route for the formation of valuable diaryl sulfides or diphenyl selenides. This simple method gives a variety of functionalized diphenyl sulfides or diphenyl selenides in moderate to good yields in a simple and efficient way.

A series of eight polymethoxychalcone Mannich base derivatives 2a-2h was synthesized via the microwave-assisted Mannich reaction of natural product 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1) with various secondary amines and formaldehyde. Compared to conventional heating method (80°C), the microwave-assisted method (700W, 65°C) is efficient with short reaction time (0.5-1 h) and good yields (74-88%). The antiproliferative activities of eight Mannich base derivatives were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) by CCK-8 assay. The results showed that all of the Mannich base derivatives exhibited potential antiproliferative activities on tested cancer cell lines with the IC50 values of 9.13-48.51 μM. Some active compounds exhibited more activity as compared to positive control cis-Platin. Among them, compound 2b revealed to have the strongest antiproliferative activity against all the three cancer cell lines with IC50 values ranging from 9.13 to 11.24 μM.

The incorporation of the modified nucleoside into the 3´-overhang regions of short interfering RNAs (siRNAs) has been reported to enhance their nuclease resistance and improve RNA interference activity. In this study, DNA 2-mers containing C5-polyamine-modified pyrimidine nucleosides were synthesized and then ligated to the 3´-end of the RNA by T4 RNA ligase. The modification of the base moiety with tris(2-aminoethyl)amine affected the ligation efficiency, but the DNA 2-mer containing only one modified nucleoside was ligated with sufficient efficiency. We propose a novel synthetic route to modified siRNA bearing various modified groups in the 3´-overhang region.

Coumarins are a class of natural and synthetic products with a wide variety of applications in different fields. Due to the general importance of coumarins, the objective of this work is to further develop the chemistry of 1-(2-hydroxy-2-methyl-2H-chromen-3yl)ethanone, 1, a potentially useful and versatile coumarin but an under-reported compound in the literature. This work describes a green preparation of 1 in the absence of solvents and acids, thereby eliminating byproducts, normally obtained in classical procedures, and a mechanistic study of the reactions of 1 with nucleophiles. In addition, we report the characterisation of 1-(2-ethoxy-2-methyl-2H-chromen-3-yl)ethanone 2, via X-ray crystallography and 2D NMR spectra.

Cycloparaphenylenes are important compounds for their photophysical and electronic properties. The curved structure of these compounds induces an alteration of the aromatic character of these compounds. D values have been used to describe the aromatic character of compounds from [5]- to [10]cycloparaphenylene. D values are compared with HOMED and with the strain energy are obtained by using an homodesmotic reaction.

An efficient synthesis of Hantzsch 1,4-dihydropyridines via a one-pot three-component reaction of ethyl acetoacetate, substituted aldehydes and ammonium acetate in the presence of ZnO@SnO2 mixed metal oxide nanoparticles under solvent-free conditions has been reported. Compare to the reported reactions, this method shows attractive aspects such as cleaner reaction profile, shorter reaction times, minimum catalyst loading and high yields. Isolated catalysts were reused for new reactions without considerable loss of their catalytic activity.

Phytosterols (PS), that is vegetable sterols, are compounds widely recognized for lowering the absorption of cholesterol and decreasing cancer risk, with βsitosterol, stigmasterol and campesterol being the most abundant. As PS is poorly soluble in aqueous solutions, many approaches have been proposed to increase their solubility and bioavailability. β-cyclodextrin (β-CD) could be used to increase PS aqueous solubility because of its capacity to entrap a variety of hydrophobic guest molecules in its cavity. In this work, the formation of β-CD/PS inclusion complexes was confirmed by Differential Scanning Calorimetry (DSC), Electrospray Ionization-High Resolution Mass Spectrometry (ESIHRMS) and Fourier Transform Infrared Spectroscopy (FT-IR), while structural characteristics were determined by one- and two-dimensional Nuclear Magnetic Resonance (NMR) techniques. Results confirmed 1:1 binding stoichiometry, which suggests the total inclusion of rings and chains of the different PS. The hypothesis of folding of the lateral chains into the cavity may be supported by the multiple correlations observed in the Nuclear Overhauser Effect Spectroscopy (NOESY) and rotatingframe Nuclear Overhauser Effect Spectroscopy (ROESY) spectra.