Design And Synthesis Of Novel Bioactive Aryl C-Glycosides

Widespread in nature, carbohydrates or saccharides show a diversity of structures and bioactivities, and are one of the most important sources of medication. Recent researches have proved they play the role as informational molecules in a lot of biological process, are responsible for various diseases. Consequently, the synthesis of functional saccharide molecules and bioactive saccharide derivatives has been focused on. In this work, three series of functional saccharide molecules were designed, synthesized and evaluated for bioactivity. Also the evaluation results were given a preliminary structure-activity analysis.1. Arbutin is a naturally occurring whitening additive. Its preparative and structure modification are of great significance. In this work, a series of novel, stable C-glycosides analogues of arbutin were designed and synthesized based on the bioisosterism. Also they were evaluated for the inhibition activity against tyrosinase. Compound 36 exibits a inhibition similar to a-arbutin in the low concentration (100μg/mL), while compound 28,30,36 display a inhibition similar to a-arbutin in the moderate concentration (200μg/mL), and compound 26, 28,30,36 show a superior inhibitory activity to a-arbutin in the high concentration (400μg/mL). These results reveal that the introduction of methyl group into the benzyl ring may lead to a decrease in inhibitory activity.2. PTP-1B has proved to be the new target for treating Type 2 Diabetes Mellitus and obesity in recent years. Aiming to seek for potential PTP-1B inhibitors with high selectivity and high activity, chloro-hydroquinonyl/chloro-benzoquinonyl C-glycosides were designed, synthesized and evaluated as a potential PTP-1B inhibitor. The evaluation results reveal that chloro-quinonyl C-glycosides exibit a moderate inhibitory activity against PTP-1B.3. Benzoquinonyl/naphthaquinonyl C-glycosides are a sort of potential enzyme inhibitors. They possess such bioactivities as anti-tumoral activity, inhibitory activity against Diabetes Mellitus and so on. In this work,6-O-benzoyl benzoquinonyl/naphthaquinonyl C-glycosides were designed and synthesized using AgOTf/SnCl4 as the promoter. Both glycosyl acetates and methyl glycosides can be used as glycosyl donors. And the latter resulted in a better stereoselectivity and thus the pureβ-conformation product. The in vitro cytotoxic activity of these compounds was evaluated against the A375 cell line. Two compounds including 6-O-benzoyl naphthaquinonyl C-glucoside (77) and 6-O-benzoyl naphthaquinonyl C-galactose (82) exhibit an expeditious and effective inhibitory activity against the A375 cell line. Results also show that the anti-tumoral activity can be obviously enhanced when naphthaquinone takes the place of benzoquinone; no significant difference can be noticed between gluco-and galacto-derivatives; the increase in the number of aromatic rings, as well as the benzoyl decoration at 6-position, may lead to the boost of activity.