Synthesis of amino-acid derivatives of chrysin

Abstract

Various conjugates of amino acids with chrysin in which the amino acid was bonded through the C-or N-terminus to the flavone were prepared using peptide chemistry methods (symmetric anhydrides and activated esters).Flavonoids are the most widely distributed compounds of natural origin. They can be found in practically all plant species. At present, flavonoids comprise about 6500 natural compounds [1]. The study of flavonoids is becoming increasingly interesting because of the important role that they play in the metabolism of plants and animals and their high and diversified biological activity [2]. Chrysin (5,7-dihydroxyflavone) is one of the most common flavonoids, has been isolated from various plant families [3,4], and possesses, like its derivatives, a broad spectrum of biological activity. Thus, chrysin exhibits anticancer [5,6], antioxidant [7, 8], anti-inflammatory [9, 10], vasodilating [11, 12], immunomodulating [13, 14], antibacterial [15, 16], antifungal [16], antiprotozal [17], neuroprotective [18], hypotensive [19], and anti-allergy [20] activity. Chrysin derivatives possess hypoglycemic [21], anticancer [22-25], anti-inflammatory [26, 27], and antibacterial [15] action.Considering the importance to the metabolism of all animals of amino acids and their derivatives, our goal was to synthesize chrysin derivatives with pharmacophores containing amino acids.The amino-acid derivatives of chrysin were synthesized via two modification pathways. The first was based on formation of the ester of N-protected amino acid and phenolic compounds. The most suitable and convenient method for synthesizing 7-O-amino-acid chromone derivatives is the reaction of 7-hydroxychromones and symmetric anhydrides of N-substituted amino acids because the reaction proceeds under mild conditions and is not complicated by side reactions [28]. It has been used successfully to synthesize similar types of compounds [29,30].The hydroxyls of 5,7-dihydroxychromones have different reactivities because of the different influence of electrondonors, steric factors, and intramolecular H-bonds. Therefore, the 7-hydroxyl of the chromone system is acylated exclusively under mild conditions [31,32].Symmetric anhydrides of N-protected amino acids were prepared by reaction of dicyclohexylcarbodiimide (DCC) with two equivalents of the corresponding N-protected amino acid in anhydrous dioxane at 0°C. The amines of the amino acids were blocked with t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), and p-toluenesulfonic acid (Tos). Chrysin was acylated by the resulting amino-acid anhydrides at 0°C in anhydrous dioxane in the presence of catalytic amounts of 4-dimethylaminopyridine (DMAP) to produce N-protected 7-O-aminoacyl-5-hydroxy-2-phenylchromen-4-ones 2-20. The products contained glycine (2, 8), L-alanine (3, 9), L-valine (4, 10), L-leucine (5, 11), L-isoleucine (6, 12), L-methionine (13), L-phenylalanine (7, 14), β-alanine (15, 17, 19), and 6-aminohexanoic acid (16, 18, 20).The selective acylation of the chromone 7-hydroxyl was confirmed by PMR ...

Synthesis of Some New Chrysin Derivatives and Their Biological Assessment as Antibacterial, Antibiofilm and Antifungal Agent

“…In chrysin C-5-hydroxyl group is relatively less reactive than C-7-OH due to steric effect and strong intra-molecular H-bonding between C-5-OH and the carbonyl oxygen (at C-4) [33]. Thus, C-7-hydroxyl group of chrysin was selectively reacted with dibromoalkane (1,2; 1,3 and 1,4) to obtain corresponding C-7-O-bromoalkyl chrysin as intermediates 1a-1c (Scheme-I).…”

“…The encouraging biological profiles of the flavonoids particularly of chrysin and in continuation of our current research interests [32] on searching and development of antimicrobial agent from natural resources led us to extend our work towards the synthesis of some new chrysin derivatives and their biological evaluations. In connection to this, it was anticipated that amines and triazole derivatives of chrysin may exhibit significant antimicrobial activity compared to the other derivatives so far reported in the literature [13,15,[33][34][35]. Therefore, 18 different derivatives (Fig.…”

Synthesis of Glycosylated Chrysin Derivatives Via Ester Linkers

“…It is reported that most of the absorbed chrysin was detectable as glucuronic acid and sulfate acid conjugates with the unprotected hydroxyl at 5-and 7-positions of chrysin in the blood and vascular system [14,15]. In order to obtain more pharmacologically active and more selective drugs with less adverse reactions for clinical use, a large number of studies have been performed via the synthesis of chrysin derivatives [16][17][18][19][20].Carbohydrates are ubiquitous in nature and play a key role in a number of important biological processes, including fertilization, cell-cell recognition, immune response, hormone regulation, and inflammation. Sugar appendages add important features to the shape and the stereoelectronic properties of a molecule and thus wield remarkable influences.…”

Synthesis of derivatives of the hydrazones of 5-phenylfuro[3,2-g]chromen-7-ones

“…The furocoumarin hydrazones 9-12 were obtained by treating alcohol solutions of the respective thiones 5-8 with hydrazine hydrate [8,9] (Schemes 1-4).…”