Selective Monomethylation of Quercetin

Abstract

Quercetin was monomethylated under mild conditions in moderate yields through selective deprotection. The combined effects of the protecting group and the heating mode on the reactivity were investigated. The presence of borax and the use of microwave irradiation significantly improved the yield and selectivity of alkylation.Quercetins [2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one] ( Figure 1) and its derivatives are widely distributed in the plant kingdom; for example, quercetin is found in the flowers of the pagoda tree, in onion, in tea, and in gingko nuts. Figure 1 QuercetinQuercetin plays a key role in the preparation of many pharmacologically active compounds. 1-4 It is of particular interest that monomethylated derivatives of quercetin exhibit anticancer, anticarcinogenic, antibacterial, antiinflammation, antiallergic, antiviral, antioxidant, antithrombogenic, and antiatherogenic properties. 3-O-Methylquercetin evidently possesses antiviral, antiinflammation, and antioxidant properties, and regulates immune functions. 5-O-Methylquercetin (azaleatin) is used to relieve cough sputum and to treat cardiovascular disease. 7-O-Methylquercetin (rhamnetin) has anti-inflammatory and antitumor properties, and resists human immunodeficiency virus. 3¢-O-Methylquercetin (isothamnetin) fights cardiovascular effects of ischemia, relieves heartstroke, regulates arrhythmia, and depresses cholesterol levels. 4¢-O-Methylquercetin (tamarixetin) has antioxidation, anticancer, and heart-stimulation effects and eliminates free radicals. These five derivatives of flavones are rarely found as natural products. However, quercetin is the main flavonoid found in foods and in plants such as Sophora japonica. Therefore, the partial synthesis of flavonoids from quercetin is would be an attractive option for the construction of monomethylated derivatives of quercetin. Although several monomethylquercetins have been prepared, 5-8 a number of challenges in their synthesis remain. These include achieving selectivity, purification from byproducts, achieving a high yield, and devising a convenient method that promotes rapid reactions, requires much less energy than existing methods, and uses lesstoxic reagents and solvents under milder conditions. Moreover, flavone derivatives are widespread and attractive components of many natural and therapeutic products of biological significance. It is therefore a desirable goal to develop an efficient, novel, simple, and convenient method for the preparation of monomethylquercetins, preferably by means of a selective one-pot reaction that will save materials and time, while giving high yields.

Evaluation of O-methyl substituted quercetin analogues as DPP-4 Inhibitor: in silico study

“…O-substitution with mono alkyl group (methyl) also shows high number of hydrogen interactions as well as novelty and feasibility in synthesis. 3,22,23 As we know DPP-4 inhibitors may be used as monotherapy or in combination with sulfonylureas, metformin, thiazolidinediones or insulin. So, inhibition of DPP4 receptor by quercetin and its analogues may be a better choice for the treatment of T2DM.…”

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

“…Until recently, selective O -methylation of quercetin was carried out by the protection of phenolic functions with benzyl or diphenylmethylene ketal [19]. Quercetin was converted to pentabenzylquercetin and thereby four mono-methylated isomers were synthesized through selective deprotection [20]. The regioselective O -methylation of kaempferol, to the best of our knowledge, has not been reported up to now.…”