Literature data up to 2003 were presented and information on methods for preparing and modifying natural 4-arylcoumarins and their synthetic analogs were systematized.The first part of this review [1] presented data on the physicochemical and pharmacological properties of natural 4-arylcoumarins. Natural neoflavones and their synthetic analogs can be used as medical preparations because of their wide spectrum of biological activity and low toxicity. However, this necessitates the development of preparative synthetic methods. Therefore, the second part reviews completely all presently known synthetic approaches to the construction and modification of neoflavones.
Coumarins in both the free state and as O-glycosides are known to be widely distributed in nature [1]. The carbohydrate unit occurs at various positions of the benzopyran ring. The sugar component of coumarin O-glycosides can be monosaccharides (D-glucopyranose, L-rhamnopyranose, D-galactopyranose, D-and L-arabinopyranose, D-xylopyranose, etc.) and also certain disaccharides. Compared with the coumarins themselves, their glycosides are very soluble in water. Considering the high biological activity of natural and synthetic coumarins and the broad spectrum of their pharmacological activity, the synthesis and investigation of biologically active glycosides of compounds based on the benzopyran-2-one skeleton is very interesting. Therefore, the present study examined the synthesis of 5-hydroxy-and 7-hydroxy-3,4-cycloannelated coumarin D-glycopyranosides and their anticoagulant activity.Hydroxycoumarins 1-3 that were required for further transformations were prepared by Pechmann condensation of polyphenols (resorcinol and orcinol) with ethyl-2-oxocyclopentanecarboxylate or ethyl-2-oxocyclohexanecarboxylate in the presence of conc. H 2 SO 4 at 0°C [2, 3]; 3-hydroxybenzo[c]chromen-6-one (4), by Hartley condensation in NaOH solution of 2-bromobenzoic acid and resorcinol with a catalyst of copper sulfate solution (10%) [4].3,4-Cyclocondensed coumarin O-glycosides were synthesized using the most convenient method based on condensation of a glycosyl donor and potassium salts of hydroxycoumarins in aqueous acetone with cooling (0°C) (Modified Michael method) and were used successfully to synthesize a similar type of compounds [5][6][7]. Solutions of these salts were prepared using equivalent amounts of the respective hydroxycoumarin and KOH solution (10%) and double (relative to the volume of base) the amount of acetone. The glycosyl donors in this synthesis were acetobromosugars (D-isomers): α-acetobromoglucose (Ac 4 GlupBr), β-acetobromogalactose (Ac 4 GalpBr), α-acetobromoxylose (Ac 3 XylpBr), and β-acetobromoarabinose (Ac 3 ArapBr), which were prepared by known methods [8,9]. The synthesis gave 42-51% yields of the O-peracetates of glucopyranosides 5 and 6, galactopyranoside 7, xylopyranoside 8, and arabinopyranosides 9 and 10, which contain a carbohydrate in the 5-or 7-position of the coumarin ring.The structures of the resulting glycosides and the configurations of their anomeric centers were unambiguously confirmed using PMR spectroscopy. The PMR spectra of 5-10 contain signals for four (for glucosides and galactosides) or three (for arabinosides and xylosides) acetyls at 2.00-2.20 ppm and signals for the carbohydrate and aglycon moieties.
A series of novel 6-pyrazolinylcoumarins has been synthesized via multi-step protocol. The synthetic procedure was based on the acetylation of hydroxycoumarins; Fries rearrangement and Claisen-Schmidt condensation; the target 6-[5-aryl-4,5-dihydropyrazol-3-yl]-5-hydroxy-7-methylcoumarins () were obtained under reactions of hydrazine and 2-aryl-5-methyl-2,3-dihydropyrano[2,3-]chromen-4,8-diones as the last phase of the protocol. Anticancer activity screening in NCI60-cell lines assay allowed identification of compound with the highest level of antimitotic activity with mean GI value of 10.20 μM and certain sensitivity profile toward the Leukemia cell lines and (GI/TGI values 1.88/5.06 μM and 1.92/4.04 μM respectively).
547.814.5 I. V. Nagorichna, and A. S. OgorodniichukAmides of 5,7-dihydroxy-4-methylcoumaryl-3-ylacetic acid were synthesized by the activated ester method using N-hydroxysuccinimide and diisopropylcarbodiimide or by reaction with N,N-carbonylimidazole. The reactivity of 3-substituted 5,7-dihydroxy-4-methylcoumarins toward 2,2-diphenyl-1-picrylhydrazyl and superoxide radical was analyzed. The effect of the synthesized compounds on xanthineoxidase activity was studied.Natural coumarins and their synthetic structural analogs possess a broad spectrum of biological activity including antiinflammatory, antibacterial, and analgesic action [1,2]. The design of new derivatives of benzopyran-2-one is often based on research of the functions of these compounds in model systems. It has been found that simple natural coumarins containing two ortho hydroxyls (6,7-dihydroxycoumarins, 7,8-dihydroxycoumarins) are effective traps for the superoxide radical and alkylperoxyl radicals and are inhibitors of peroxide oxidation of lipids. However, these compounds in the presence of iron ions can also be prooxidants that are capable under certain conditions of stimulating undesired redox transformations involving molecular oxygen. Therefore, coumarin derivatives containing meta dihydroxyls are definitely interesting for constructing potential synthetic antioxidants. Thus, 5,7-dihydroxy-4-methylcoumarin is not a pro-oxidant, inhibits peroxide oxidation of lipids, and reacts with active oxygen species and hypochlorite [3]. Besides, it inhibits transformations catalyzed by cyclooxygenase and does not affect the activity of 5-lipoxygenase [2,4,5].Because of the importance of the 5,7-dihydroxy-4-methylcoumarin moiety in the structure of a potential antioxidant, we attempted to analyze certain properties of 5,7-dihydroxy-4-methylcoumarins containing 3-substituents. A series of structurally similar amides was synthesized using 5,7-dihydroxy-4-methylcoumarin-3-ylacetic acid as starting material. Their reactivity toward 2,2-diphenyl-1-picrylhydrazyl and superoxide radical was studied. The effect of the synthesized compounds on xanthineoxidase activity was also found. 5,7-Dihydroxy-4-methylcoumarin-3-ylacetic acid (2) that was required for subsequent transformations was prepared by saponification of the ester in 5,7-dihydroxy-4-methylcoumarin (1) by NaOH in aqueous propan-2-ol with subsequent acidolysis of the reaction mixture. Coumarin 1 was synthesized by condensation of phloroglucinol dihydrate and dimethylacetylsuccinate in the presence of dry HCl.Amides of 2 were prepared by two methods. The first used N-acylation based on the activated ester method that is used commonly in peptide synthesis [6]. The carboxylic acid was activated using a highly reactive N-hydroxysuccinimide ester [7]. The activated ester was prepared by reacting 2 and N-hydroxysuccinimide (SuOH) in absolute dioxane using diisopropylcarbodiimide (DIC) as the condensing agent. Condensation of the resulting activated ester with amines in dioxane at room temperature formed amides...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.