Synthesis of Quercetin Glycosides and Their α-Glucosidase Inhibitory Activities

Abstract

A series of quercetin glycosides as the analogues of 3,5,5'-trimethyl-7-O-β-D-glucopyranosylquercetin (8) were synthesized, their structures were confirmed by 1 H NMR, 13 C NMR and MS. The inhibitory activities of those compounds against α-glucosidase were evaluated in vitro, in particular, the compounds V-c and V-d-2 showed promising bioactivities with IC50 of 19.4 μmol•L-1 and 19.7 μmol•L-1 , are much higher than 8 (IC50 > 100 μmol•L-1). This research will provide a reference in the study of the synthetic methods and hypoglycemic activity for the quercetin glycosides. Diabetes mellitus is metabolic disorder characterized by insufficient secretion or inefficient processing of hormonal insulin and it is becoming the third leading cause of death, after cancer and cardiovascular diseases. 1 The number of people with diabetes has increased from 153 million in 1980 to 382 million in 2013. The International Diabetes Federation (IDF) predicted that the number of people with diabetes will increase to 435 million in 2030. 2 One of therapeutics for diabetes is inhibition of α-glucosidase which is the key enzyme of carbohydrate digestion by specifically hydrolyzing the α-glucopyranoside bond to release α-D-glucose from the non-reducing end of the sugar. Therefore, the inhibition of α-glucosidase is an effective approach in preventing and treating diabetes through reduction of postprandial hyperglycaemia. 3,4 At present, though some inhibitors have potent effect on α-glucosidase, the corresponding side effects cannot be ignored. For example, acarbose probably causes abdominal distension, flatulence and meteorism. 5 In recent years, large amount of synthetic chemicals or natural products have been screened to get more effective and safe α-glucosidase inhibitors. 6 Searching lead compounds from natural products

Advances on Synthesis of Flavonoid Glycosides

“…继 2015 年报道全合成鱼腥草素 B 之后, 2018 年报 道了全合成了鱼腥草素的重要成员之一鱼腥草素 A (20) [42] , 类似上例合成鱼腥草素 B 一样, 首先合成目标 如以芦丁(21)为原料, 经 过苄基化、酸水解得到苄基保护的槲皮素, 再与乙酰基 保护的溴代糖进行糖苷化反应, 然后经过去乙酰基和去 苄基等步骤获得系列槲皮素 3-糖苷、3,4'-O-二糖苷和 3,7-O-二糖苷 [43] . 由于共轭效应而使得槲皮素的 7、4' [44,45] (Scheme 4).…”