Copper-Catalyzed Cross-Dehydrogenative Coupling of α-Hydroxy Esters with Nitromethane

An efficient copper-catalyzed tandem oxidation/nitro-aldol reaction of hydroxyl compounds with nucleophiles is developed. In this work, β-nitro-α-hydroxy esters were prepared via cross-dehydrogenative coupling reaction using α-hydroxy esters as hydroxyl compounds and nitromethane as a nucleophile. The reaction is believed to undergo an oxidation of hydroxyl group and then an addition of the generated carbonyl group. It’s an example of CDC reactions related to hydroxyl compounds via carbonyl intermediates.

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Protein kinase CK2 has been considered as an attractive drug target for anti-cancer therapy. The synthesis of N-hydroxypropyl TBBi and 2MeTBBi derivatives as well as their respective esters was carried out by using chemoenzymatic methods. Concomitantly with kinetic studies toward recombinant CK2, the influence of the obtained compounds on the viability of two human breast carcinoma cell lines (MCF-7 and MDA-MB-231) was evaluated using MTT assay. Additionally, an intracellular inhibition of CK2 as well as an induction of apoptosis in the examined cells after the treatment with the most active compounds were studied by Western blot analysis, phase-contrast microscopy and flow cytometry method. The results of the MTT test revealed potent cytotoxic activities for most of the newly synthesized compounds (EC50 4.90 to 32.77 µM), corresponding to their solubility in biological media. We concluded that derivatives with the methyl group decrease the viability of both cell lines more efficiently than their non-methylated analogs. Furthermore, inhibition of CK2 in breast cancer cells treated with the tested compounds at the concentrations equal to their EC50 values correlates well with their lipophilicity since derivatives with higher values of logP are more potent intracellular inhibitors of CK2 with better proapoptotic properties than their parental hydroxyl compounds.

SCIENTIFIC AND TECHNOLOGICAL FEATURES OF SYNTHESIS OF NEW ESTER PLASTICIZERS BASED ON RENEWABLE RAW MATERIALS

Methods for the synthesis of ester non-toxic biodegradable plasticizers (hazard class 4) using renewable raw materials have been developed: glycerine-containing waste generated in the production of biofuels; citric acid 244, by microbial synthesis from molasses sugar production waste; polyatomic alcohol (neopoliol) – trimethylolpropane – a product of oxosynthesis obtained on the basis of natural gas. The target products are esters with a molecular weight range of 250-600, with low saturated vapor pressure, good thermal stability and polymer compatibility, and chemical inertia. The results of complex researches of processes of esterification of carboxylic acids with hydroxyl compounds in industrial homogeneous catalysts of different acidity (sulfuric acid, p-toluensulfonate, phosphoric acid) allowed determining the main approaches to the selection of raw materials chemical composition. This took into account the availability and toxicological characteristics and evaluation of the technological characteristics of esterification process to increase the conversion of raw materials and achieve a high selectivity for the target product. It is shown that to overcome the thermodynamic limitation in all processes, it is necessary to use a 6-7-fold molar excess of the second reagent: acid or alcohol. A solvent (benzene, toluene) is added to the initial mixture, which maintains a constant temperature and removes the reaction water in the form of an azeotrope. To isolate the target products from the reaction mass, it is proposed to use a film evaporator operating under vacuum (p=5-10 mm Hg, t=105-120 ℃). Samples of tributyrin glycerin, triamyl citrate and triethanoate purity ≥ 98% were obtained. The main physical-chemical properties were determined. A comparison with known industrial analogues was carried out. Evaluation of key quality indicators confirms the possibility of their use as plasticizers in the formulation of PVC pastes.

Nematicidal Streptomyces against Meloidogyne incognita by hydrosoluble macromolecules

Background: Although actinomycetes, which produce antibiotics, have been reported to produce nematicidal metabolites, macromolecules with nematicidal activities have rarely been described. Results: The culture filtrates of Streptomyces albogriseolus strain DN41 and S. fimicarius strain D153 presented 82.13 % and 86.96 % nematicidal activity against Meloidogyne incognita, respectively, after 12 h. A pot experiment highlighted that these culture filtrates were characterised by significant efficacy. The biocontrol efficiency of strain DN41 reached 61.68 % and that of strain D153 68.33 % after 30 days at a dose of 100 mL pot-1. The active metabolites produced by the two strains were hydrosoluble and sensitive to heat, with molecular weights above 8000 Da for DN41 and of 1000–8000 Da for D153. However, these metabolites were negative to protein reaction. A chemical characteristic test indicated that these active metabolites were polar polymers that contained a large amount of sugar and phenolic hydroxyl compounds. Conclusions: These results revealed S. albogriseolus strain DN41 and S. fimicarius strain D153 as potential agents for the control of root-knot nematodes, as hydrosoluble macromolecules have good compatibility and are convenient for practical application.