甘草素與氮醣之研究:I 合成甘草素衍生物作為抗SARS冠狀病毒試劑II 氮醣之合成與醣化合物在水相中之反應

Abstract

This thesis consists of two parts. In the first part, we already synthesize glycyrrhizic acid derivatives as the antiviral angents against severe acute respiratory syndrome corona virus (SARS–CoV) agents. In the second part, we synthesize azasugars and explore some reactions of saccharides in I2/NH3 aqueous solution. Glycyrrhizic acid is known to exhibit wide range of biological activities, for example, anti–inflammatory, anti–allergic, anti–dote, antioxidation and anti–tumor activities. However, the mechanism of glycyrrhizic acid in vivo is still unclear. It is reported that glycyrrhizic acid has the activity to inhibit the replication of the SARS coronavirus,but the inhibition concentration is still high. Consequently, it is desirable to find better SARS–CoV inhibitors by modification of glycyrrhizic acid. The structure of glycyrrhizic acid consists of two parts, one is 18β glycyrrhetinic acid and the other is disaccharide. I carried out a research work to replace the disaccharide part by other important saccharides, e. g., sialic acid and GlcNAc, to obtain compounds 25 and 26. By comparision of the inhibitory activity of glycyrrhizic acid (EC50 =1mM), we found that compound 25 greatly improves the inhibitory activity (EC50 = 20 μM) against the infection of SARS coronavirus on Vero E6 cells. Antibiotic resistance is a serious problem in many diseases. transglycosydase is one of enzyme in essential of bacterial cell wall synthesis. We desire to synthesize azasugars as transglycosydase inhibitors. In this part, we have synthesized the backbone structure of azasugars. In another approach, we found GlcNAc was degraded by I2 and ammonia water. We also found that saccharides can be linked with primary amines in aqueous solution by the promotion of I2. This novel type reaction is potentially useful in carbohydrate chemistry, such as in preparation of glycopetide in future.