Modified Coumarins. 17. Synthesis and Anticoagulant Activity of 3,4-Cycloannelated Coumarin D-Glycopyranosides

Abstract

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.

Antagonists of Vitamin K—Popular Coumarin Drugs and New Synthetic and Natural Coumarin Derivatives

“…Garazd et al synthesized several 5-hydroxy-and 7-hydroxy-3,4-cycloannelated coumarin D-glucopyranosides (by condensation of potassium salts of hydroxycoumarins and acetobromosugars) [107]. Compared with the parent coumarins, their glycosides ( Figure 10) are very soluble in water.…”

Microwave‐Expedited Green Synthesis, Photophysical, Computational Studies of Coumarin‐3‐yl‐thiazol‐3‐yl‐1,2,4‐triazolin‐3‐ones and Their Anticancer Activity

“…The special framework of lactone ring with the conjugated system enables it to interact with various enzymes and receptors in organisms . Thus coumarin has intrigued substantial interest in pharmacological activities like anti‐inflammatory,, antioxidant, anticoagulant, antituberculosis, antinociceptive, antimicrobial,, antidepressant, cyclooxygenase inhibition and anticholinesterase activities . Among all these versatile biological activities, coumarins are notably accounted for their anticancer activities .…”

Antimicrobial Properties of Newly Synthesized Derivatives of Coumarine

“…Although coumarins have been known for many years, the researche about their properties such as anticoagulant (Garazd et al, 2005;Katritzky et al, 1996;Manolov and Danchev, 1995), antibacterial (Arora and Mathur, 1963), antiinflamatory (Al-Haiza et al, 2003), antioxidant, activities has become duty and responsibility for researchers to discover new methods of synthesizing new biological active coumarins.…”