Abstract:This paper is to analyze the latest data on synthesis, structure, chemical and biological properties of flavonoid dihydroquercetin (taxifolin). Complexes including DHQ (dihydroquercetin) into cyclodextrins were obtained. These supramolecular representatives are characterized by high water-solubility, good permeability through biomembranes, prolonged action in the organism and stability while being transported in bloodflow. The use of DHQ in complex with β-cyclodextrin is more promising from the medical point of view than the use of pure DHQ. Total and partial acidylation of DHQ with acid chlorides of aliphatic, aromatic, and heterocyclic carboxylic acids, as well as selective phosphorylation with acid derivatives of trivalent phosphorus (with amides and amidethers of phosphorous acid), and aminomethylation were carried out. DHQ freely undergoes Mannich Reaction with formaldehyde and amines of various structures. The products of the reaction are isolated from the reaction mix with good yield. Isolated aminomethylated derivatives have neurotropic and antiproliferative action.The structure of all synthesized compounds was proved with the help of modern methods of analysis: spectroscopy NMR ( 1 H, 13 C) and XRS. Biological activity of dihydroquercetin modified derivatives was studied. It was found out that some of them are characterized by high cytotoxic, antitumour, and antioxidant biological activity. The inclusion complexes of dihydroquercetin and cyclodextrin were obtained. Acylation, phosphorylation and aminomethylation of dihydroquercetin was performed. The biological activity of obtained compounds was studied.
The flavonoid dihydroquercetin and its esterified derivatives possess various biological activities and are widely used as dietary supplements and in pharmacology. A significant disadvantage of this flavonoid is its low solubility in water at ordinary temperatures of up to 0.03%, which negatively affects its biological activity. Nature overcomes this problem by glycosylation, sulfation, and phosphorylation. In chemistry and pharmacology to overcome this problem, there are several synthetic approaches. For dihydroquercetin (DHQ) is the inclusion of DHQ in the cyclodextrin matrix or the formation of a complex of DHQ with basic natural amino acids. In this paper, a method is proposed for obtaining water-soluble morpholinium salts based on chloroacylated derivatives of DHQ. The acylation reaction was carried out in dioxane, pyridine was used as an acceptor of choric hydrogen. The target compounds were obtained with a yield of 68-79%. As a result, chlorinated derivatives based on DHQ and its acyl and benzyl derivatives were synthesized. These derivatives in the interaction with morpholine form its salts, which, as it turned out, have a high water solubility. Pentamorpholine salt of DHQ had the highest solubility in water, up to 6.5% at room temperature, which is 200 times more soluble than the original DHQ. The proposed synthetic approach to increase the water solubility of acyl derivatives of DHQ can be extended using other nitrogenous bases and other haloacyl derivatives of DHQ.
The paper describes methods for the transformation of poorly water-soluble flavonoids: dihydroquercetin, catechin and quercetin into water-soluble forms during the formation of supromolecular adducts with β-cyclodextrin and salt-type ionic complexes with the natural amino acid L-arginine, which contains a guanidine moiety properties necessary to create a cationic structure when interacting with phenolic groups. First, a methodology was developed for the synthesis of supromolecular structures, in which flavonoids were incorporated into a cyclodextrin matrix. As a result, the solubility in water at 20 °C of encapsulated flavonoids increased by more than two orders of magnitude. In the formation of complexes of cyclodextrin with flavonoids, the main role is played not by hydrogen bonds between the hydroxyl groups of flavonoids and β-cyclodextrin - in the case of dihydroquercetin and catechin, they are different and similar in the case of dihydroquercetin and quercetin, but the spatial orientation of the pyrocatechol cycle B (due to the flat conjugation of the entire molecule and due to sp2 is the structure of the second carbon atom of the pyran ring). Another implemented approach for obtaining water-soluble flavonoids at room temperature is the creation of their salts with the natural amino acid L-arginine, which is a part of proteins and is involved in several vital processes in the body. The structure of the obtained compounds was proved by the methods of NMR spectroscopy on 13C nuclei and X-ray structural analysis, the composition – by elemental analysis.
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