| Oseltamivir phosphate is the first orally active inhibitor of influenza virus neuraminidase,which is used to alleviate the symptom of influenza,shorten the course of disease and decrease complicating disease.Especially Oseltamivir phosphate take effects on the bird flu,so nowdays it is one of the best antivirus drugs ,and there is big market demamd.Since Oseltamivir phosphate was invented in Switzerland in 1996, Synthetic method, physiological activity and clinical application of Oseltamivir phosphate was studied intensively internationally,But little effort was done athome. In this article we do some reseach on Oseltamivir phosphate and its intermediates, in order to provide a stable, rational preparation technology of Oseltamivir phosphate and the related datas andgraphs.In this experiment shikimic acid was extracted and purified from natural product star anise,then Oseltamivir phosphate was prepared from shikimic acid after 11 step reactions via methyl (3R,4R,5S)-4,5-Epoxy-3-methoxymethoxy-Cyclohexene-1- carboxylate ,and the all yield is 12.4%. 15 componds was prepared,some of the compands was tested by infrared absorption spectrometry, Mass Spectrometry and element analysis.In the article each critical unit reaction was promopted:①the shikimic acid was purified in advantage of its aqueous solubility;②Thionyl chloride was take place by triphosgene which is more environmentally friendly;③Trimethyl borate was take used as dehydrant ,which increase the yield;④Perchloric acid was taken place by Trifluoromethanesulfonic acid ,and it make reaction more safer;⑤After feeding sequence was adjiusted ,the yield was improved;⑥In order to increase the yeild,pyridine was taken place by DBU;⑦Azido was reduced by ammonium chloride/zinc dust system,Ithas excellent results and is easier to operate.In the articale the analytic result were discussed in details,and we also provide the IR spectrums ,MS spectrum and element analysis results.wehope these datas canhelp the other profession. |
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