| Adefovir dipivoxil is an HIV nucleoside inhibitor named [[2-(6-amino-9H-purine-9-yl)ethoxy]methyl]phosphoric acid2-(Special E acyloxo methyl)ester which is developed first in the United States by the Gilead Sciences company at2002with named Hepsera. This product is the ester prodrug adefovir, with broad-spectrum antiviral activity, inhibit the hepatotropic virus, retrovirus and herpes virus. Therefore, the successful research of this agent will improve the present situation that many patients cannot get the effective therapy, and it possesses tremendous social and economic benefit. To this artic, the author designed a new synthetic route of adefovir dipivoxil and performed it after refered th prior route of synthesis. As a result, the yield of intermediats was improved, and their purification operative procedure was simplified. At the same time, the cost was cut down, and environmental pollution was diminished. The main content of this paper are as follows:A new synthetic route of9-[2-Phosphonylmethoxyethyl]adenine was designed, used bromotrimethylsilane instead of trimethyl chlorosilane/sodium iodide, and the yield can reach62.1%. Adefovir dipivoxil was synthesized, replaced N, N’-Dicyclohexyl-4-morpholine carboxamidine for N-Methyl pyrrolidone. However, because of the low yield and unstable of the last step reaction to the ester, prevented our company to expand the scale of production, and affecting the cost of this goods. Therefore, reagents were selected through the re-combination reaction sequence, optimization of reaction temperature and change reaction time and other methods to re-modify or optimize the process.In conclusion, through the new synthetic route of adefovir dipivoxil, the yields of intermediats were improved, and purification operative procedure was simplified. At the same time, the cost was cut down, and environmental pollution was diminished. All of these provide the theoretical and experimental evidence for industrialization production of adefovir dipivoxil. |
PDF Full Text Request