Design And Synthesis Of Flavonoid Class Of Vif-A3G Inhibitors

Flavonoids (2-phenyl chromone) exist in nature with extensive activities especially for HIV-1. It has already been found that 6-21 which is a derivative of quercetin could inhibit HIV-1 Vif-A3G effectively.8-sulfonic group of 6-21 could enhance the activity. Therefore, a series of flavonoid derivatives may be developed to disrupt the interaction with Vif-A3G.Firstly, Computer Aided Drug Design was used to establish a pharmacophore model and dock.6-21 could match the pharmacophore very well. In addition, the sulfamine is a vital group. Therefore, a series of flavonoid-8-sulfamine derivatives were designed. Moreover, by LigandFit of Discovery Studio, the prominent activity of the compounds has been predicted in the key sites of A3G-Vif in manner of hydrogen bond andπ-σinteraction.Secondly, the hydrolysis reactions of flavonoid glycosides were performed to form raw materials of the target compounds. CT-450 was used as a catalyst instead of the traditional proton acid. Meanwhile, water acts as the solvent which provids a mild condition. A convenient, high-convertible, and recyclic method was found. In addition, the recycle had few effect on the yield. Two routes were carried out to modify the flavonoids. In route 1, the mono-sulfonated sodium and di-sulfonated sodium of flavonoids were obtained through adjusting the reaction temperature. Moreover, the crystal structure of 6 was determined by X-ray diffraction. However, the target compounds were not generated with acetyl protective group. In route 2, acetyl group was insteaded by methyl group. Chlorosulfonic acid was used to be sulfonylation agent. Three sulfamide derivatives of quercetin were synthetized and their structures were confirmed by 1HNMR,13CNMR, MS, et al.