Synthesis Of Flavonol Glycosides And Total Synthesis Of Delavatine A

Flavonol glycosides widely occur as natural products. They act as active components of many medical plants and exhibit various bioactivities. In this thesis a series of flavonol glycosides were synthesized. This serves as a basis for testing their bioactivities, revealing the relationships between structure and bioactivity and developing new medicines. Delavatine A was isolated from Incarvillea delavayi and demonstrates strong antitumor activity. Its skeleton has not been reported. In this thesis, its skeleton was successfully constructed via a key cascade reaction and we finished the total synthesis of Delavatine A.(1) Synthesis of Kaempferol 3-O-(3",6"-Di-O-E-p-coumaroyl)-β-D-glucopyranosideKaempferol 3-0-(3",6"-di-O-E-p-coumaroyl)-β-D-glucopyranoside 1, an optimal metabolite of Scots pine seedlings for protection of deep-lying tissue against damaging UV-B, represents a typical acylated flavonol 3-O-glycoside. This compound was synthesized for the first time via two approaches. The first approach, starting with kaempferol, featured formation of the flavonol 3-O-glycosidic linkage with a glycosyl bromide under conventional PTC conditions. In the second approach,5,7,4'-tri-O-benzyl kaempferol was readily prepared from 2',4',6'-trihydroxyacetophenone and p-hydroxybenzoic acid, which was coupled with a glucopyranosyl ortho-hexynylbenzoate under the catalysis of a gold(I) complex to provide the desired 3-0-glycoside in excellent yield. A variety of the glycosyl ortho-hexanylbenzoates were also proven to be highly efficient donors for construction of the flavonol 3-O-glycosidic linkages.(2) Efficient Synthesis of Kaempferol 3,7-0-BisglycosidesSelective glycosylation of the 3-OH of 5,4'-di-O-acetyl-kaempferol was achieved with glycosyl ortho-alkynylbenzoates as donors under the catalysis of Ph3PAuNTf2, and subsequent glycosylation of the remaining 7-OH with glycosyl trifluoroacetimidates under the catalysis of BF3-OEt2, after global deprotection, afforded the kaempferol 3,7-O-bisglycosides conveniently(3) Synthesis of Kaempferol-5-O-rhamnopyranosideFlavonol Glycosides 50 and 51 are representative flavonol 5-O-rhamnopyranoside. Because of the strong intramolecular H-bond, the 5-O-glucosidic linkage could not be efficiently constructed via conventional glycosylation method. In this paper, we use a novel glycosylation method which is gold (I)-catalyzed glycosylation method with glycosyl ortho-alkynylbenzoates as donor to efficiently achieve the formation of the challenging Kaempferol-5-O-glycosidic linkages, and finally leading to naturally occurring compounds 50 and 51.(4) Carbonylation of Aryl and Heteroaryl BromidesEfficient alkoxycarbonylation of (hetero)aromatic bromides was achieved under the presence of atomospheric pressure of carbon monoxide with the in situ generated palladium/rac-BINAP as catalyst system, n-BuOH as solvent and Et3N as base.(5) Total synthesis of Delavatine ADelavatine A is an Isoquinoline alkaloid with 4-aza-acenaphthylene skeleton which was reported in nature product for the first time. This skeleton was constructed via a key stille-Heck cascade reaction and we finished the total synthesis of Delavatine A.