Vanillic Acid Sugar Ester Glycoside Synthesis

It is well known that the modification of drug with sugar and its derivates may yield big changes in water-solubility, promote absorption, reduce toxicity and other side-effect, enhance drug's efficacy. The modified drug may cooperate with the primary medicine on disease-resistant function. As reported by many literatures, vanillic acid had various biological effects and pharmacological activities, such as anti-oxidation, antibacterial activity, and effect of adjusting nerve, and so on. Therefore, decorating structure of vanillic acid was maybe helpful to discover compound that had more efficacy. This work may help to the research and the development of new medicine.Up to now, the report of vanillic acid modified with the sugar was very few either in domestic or in overseas. This paper attempted to decorate structure of vanillic acid with inexpensive glucose, xylose, galactose, maltose, lactose and rhamnose. Seven vanillic acid sugar esters, which are all new compounds but la, was designed and synthesized. We prepared O-acetylglucopyranosyl bromide, O-acetyl galacopyranosyl bromide, O-acetylmaltose bromide, O- rhamnose bromide, O-acetylxylopyranosyl bromide and O-acetyllactosyl bromide respectively, then coupled them with vanillic acid in the presence of Ag₂O.This paper firstly reported the synthesis of vanillic acid-4-β-D-2',3', 4',6'-acetylglucoside-1-β-D-2",3",4",6"-acetyl glucoester(1b), vanillic acid-4- β -D-2',3',4',6'-acetylgalacoside-1-β-D-2",3", 4", 6"- acetyl galacoester (2b) by the reaction of vanillic acid with O-acetyl glucopyranosyl bromide and O-acetylgalacopyranosyl bromide in the presence of Bu₄NBr. Meanwhile, under the system of NaOH/acetone, we also succeeded in synthesizing the two compounds above.The entire reaction route included the builting of monosaccharide donor moiety and the synthesis of sugar ester. This work mainly involved the protection of hydroxyl acetylated, the activation of anomeric carbon, the formation of the bond of sugar ester and the bond of glucoside. And the mechanism of phase transfer catalyst reaction was...