| Flavonol glycosides are present in wide variety of fruits,vegetables,and herbal medicines.These compounds show a broad range of biological and pharmacological activities including antioxidant,anticancer,and radical scavenging activities.Recently,our laboratory has separated a flavonol glycoside,trans-tiliroside from Rosa canina.It was first reported that these kind of flavonol glycoside compounds have potent anti-obese and anti-diabetic activity.Therefore,it is valuable for further biological evaluation.This paper describes the first chemical synthesis of isoquercitrin coumarate(1)and quercetin 3-O-[6"-O-(p-hydroxyphenylpropionyl)]-β-D-glucopyranoside(2)via quercetin 3-O-β-D-glucopyranoside(isoquercitrin,3)as a intermediate.The synthesis was started from commercially available quercetin via regioselective benzylation of quercetin to produce 4’,7-di-O-benzylquercetin.Kaempferol 3-O-β-D-glucoside(4)and kaempferol(5)was synthesized from 2,4,6-trihydroxyacetophenone through ten steps with 15%over all yield.Here we developed a novel glycosylation method by using NaH.This strong base can break the hydrogen bond between 3-OH and 4-carbonyl group of resokaempferol and enhance the nucleophilicity of hydroxyl group.Resokaempferol 3-O-β-D-glucoside(7)was first synthesized from inexpensive 2,4-dihydroxyacetophenone through six steps with 40%over all yield.Base upon the previous synthetic study,we designed and synthesized 28 compounds through further modification for development of effective antidiabetic agents.The target compounds and their intermediates were confirmed by FT-IR,1H NMR,13C NMR,1H-1H COSY,1H-13C HSQC,1H-13C HMBC,DEPT,and ESI-MS.The target compounds had been extensively evaluated for the anti-obese and anti-diabetic activity and some of them exhibited excellent activities.Base upon the results of the pharmacological results,the structure-activity relatonships(SAR)were briefly.summarized in this thesis for further studies. |
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