沒食子酸葡萄醣酯類衍生物之合成研究

Synthesis of Galloylglucose Analogues

顏志政

指導教授 ： 陳繼明

臺北醫學大學/藥學院/藥學研究所/碩士(1995年)

摘要

沒食子酸葡萄醣酯類是一種廣泛分佈於植物界中的酚性化合物。從化學結構式上來看，它們具有以酯鍵連結數個沒食子酸於一個葡萄糖基上的特徵。在藥理作用方面，發現沒食子酸葡萄醣酯類除了具有抗菌活性，降低血中尿氮素值及抗脂質氧化的活性外，另外還有抑制血管緊縮素轉化酵素的活性。為了要進一步研究其對於心血管系統之藥放作用及化學結構關係，我們利用化學合成的方法針對沒食子酸葡萄醣酯類的結構作一些修飾，合成了一系列具有酚性取代基之安息香酸及桂皮酸與葡萄糖縮合成形成酯類之相關類似化合物，然後將再分別作藥理測試降血壓藥放以作為評估的依據。 　　化學合成方法係以methyl ?α-D-glucopyranoside 及一系列以四氫?喃基或?基保護酚性取代基之安息香酸及桂皮酸為起始物，首先利用Keck修飾的Steglich酯化法縮合形成葡萄糖酯類化合物，其產率約在50%至90%之間，然後，再經酸催化或氫化還原反應，切除保護基，即可得到最終產物： methyl 2,3,4,6-tetra(p-hydroxybenzoyl)-α-D-glucopyanoside(la), methyl 2,3,4,6-tetraprotocatechuoyl-α-D-glucopyranoside(lb), methyl 2,3,4,6-tetragalloyl-α-D-glucopytanoside (lc), methyl 2,3,4,6-tetracaffeoyl-α-D-glucopyranoside(ld), methyl 2,3,4,6-tetracaffeoyl-α-D-glucopytanoside (le), and methyl 2,3,4,6-tetraferuloyl-α-D-glucopyranoside(lf)。 　　此六種目的化合物經紅外光譜、氫光譜、碳光譜及質譜光譜分析確定其化學結構，其有關心血管系統之藥理作用則正在試驗中。

關鍵字

沒食子酸葡萄醣酯類 ； 酚性化合物

並列摘要

Galloyglucoses are a group of phenolic compounds widely distributed in the plant kingdom. Structurally, they are characterized by several molecules of gallic acid attached to a β-D-glucopyranose through ester linkage. Recent reports indicated galloylglucoses displaying antibacterial activity, lowering the level of blood urea nitrogen, inhibiting of lipid peroxidation and inhibition the activity of angiotensin converting enzyme.We wish to report the synthesis of galloylglucose analoges by incorporation of phenlic benzoyl and cinnamoyl moeity into D-glucoses molecule and these phenolic compounds will be evaluated their activity on cardiovascular system. 　　Coupling of methyl α-D-glucopyranoside with tetrahydropytanyl or benzyl protected hydroxy group in substituted cinnamic acids and benzlic using the Keck modification of the Steglich esterfication oumaroyl the glucose esters in isolated yield of 50%-90%. Following cleavage of tetrahydropyranyl and benzyl proteitiog groups by strong acidic resin and hydrogenation, respectively, afforded the final products. They are methyl 2,3,4,6-tetra(hydroxybenzoyl)-α-D-glucopyranoside(la), methyl 2,3,4,6-tetraprotocatechuoyl-α-D-glucopyranoside(lb), methyl 2,3,4,6-tetragalloyl-α-D-glucopyranoside (lc), methyl 2,3,4,6-tetracaffeoyl-α-D-glucopyranoside(ld), methyl 2,3,4,6-tetracaffelyl-α-D-glucopyranoside (le), and methyl 2,3,4,6-tetraferuloyl-α-D-glucopyranoside(lf). 　　The structures of these compounds are consistent with their spectral data of the IR,1H-NMR,BC-NNR and Mass spectra.