| Summary: | 碩士 === 國立中央大學 === 化學研究所 === 99 === Hepatitis C virus (HCV) constitutes a global health problem with 170 million people infected worldwide. In Taiwan HCV is a contagious viral disease that leads to serious, permanent liver damage and in many cases death. In recent years, using nucleoside to be anti-virus and anti-cancer drugs case is increased and the suppression of the virus had good inhibitory activity, we using guanosine as the main antiviral research. We hope that the guanosine derivatives which synthesized in our laboratory has the anti-HCV activity.
We carried out the reaction between triethylamine and guanosine in dichloromethane, and added coumarin-3-carboxylic chlorides at 0?C, then we used tetrabutylammonium fluoride solution to get N2-(coumarin-3''-carbonyl)guanosine. We carried out the reaction between triethylamine and guanosine in chloroform, and added 3-(chloromethyl)coumarins at 50?C, then we used tetrabutylammonium fluoride solution to get N2-[(coumarin-3''-yl)methyl]guanosine.
We used nuclear magnetic resonance spectra of hydrogen (1H NMR) to comfirm characteristic peak’s chemistry shift. We used mass spectrometry (FAB Mass) to comfirm the m/z ratio of the compoumd, and infrared spectroscopy (FT-IR) to confirm the -NH and –OH group. The stable amide linker compounds shows intramolecular hydrogen bonding. By using the NMR we can observe characteristic peak for N-1 binding site at 5.15 ppm and for N-2 binding site at 4.36 and 5.05 ppm. When we compared the water solubility between 1a and 2, the compound 1a which contain furanose group has the water solubility 71.0 ?g/mL. Therefore compound 1a result in increase in oral absorption and good permeation rate across the intestinal mucosa into the circulation. Then we used 1H NMR and molecular simulation to discuss the stereo structure and conformation. The results can help us to discuss the structure and activity relationship (SAR). In future we can use the above results to develop more resistance drugs to inhibit hepatitis C virus (HCV).
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