磷酸奥司他韦的合成

中国药物化学杂志 Pub Date : 2009-01-01 DOI:10.1055/s-0032-1317719

Lin Lin, Wang Zhe-jiang, Mao Dong-dong, X. You-jun

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引用次数: 0

摘要

目的研究抗病毒药物磷酸奥司他韦的改进合成工艺。方法以莽草酸为起始原料，经酯化、酮化、甲酰化、转酮化、还原和分子内SN2反应，合成关键中间体(3R,4S,5S)-4,5-环氧-3-(1-乙基-丙氧基)-1-环己烯-1-羧酸乙酯(2)。在MgCl2存在下，用叔丁胺对2进行开环氧化处理，然后进行甲基化和分子内SN2反应，生成(3R,4S,5R)-4,5-(1,1-二甲基乙基)亚胺-3-(1-乙基丙氧基)-1-环己烯-1-羧酸铵氮吡啶乙基。msoh促进氮吡啶与二烯丙胺开孔，然后乙酰化，依次去除叔丁基和烯丙基，最终得到奥司他韦。结果与结论经13步合成磷酸奥司他韦，总收率为29.5%，并通过1H-NMR和MS对其结构进行了鉴定。

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Synthesis of oseltamivir phosphate

Aim To investigate an improved synthetic process of oseltamivir phosphate,an antiviral drug.Methods Starting from(-)-shikimic acid,the key intermediate ethyl(3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-1-cyclohexene-1-carboxylate(2) was synthesized via esterification,ketalization,mesylation,transketalization,reduction and intramolecular SN2 reaction.2 was treated with tert-butylamine for epoxide-opening in the presence of MgCl2,and then brought into mesylation and intramolecular SN2 reaction to form the aziridine ethyl(3R,4S,5R)-4,5-(1,1-dimethylethyl) imino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate.After MsOH-promoted opening of the aziridine with diallylamine,followed by acetylation and successive removal of tert-butyl and allyl group,oseltamivir was eventually obtained.Results and conclusion Oseltamivir phosphate was synthesized via a 13-step sequence in a total yield of 29.5% and its structure was identified by 1H-NMR and MS.

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来源期刊

中国药物化学杂志

自引率

0.00%

发文量

3349

期刊介绍： The Chinese Journal of Medicinal Chemistry is jointly sponsored by Shenyang Pharmaceutical University and the Chinese Pharmaceutical Society. It is the only professional academic journal in China that specifically reflects the scientific research results and scientific and technological information in the field of medicinal chemistry. Its purpose is to stand at the forefront of the development of medicinal chemistry today, report the latest scientific and technological trends and scientific research results of the discipline, provide a window for the vast number of medical and scientific workers to understand new drug research, pharmaceutical process research, and natural drug chemistry research, and promote the development of the world's pharmaceutical industry. The readers are researchers in the fields of pharmacy, chemistry, biology, and traditional Chinese medicine in drug research institutes, research institutes, and pharmaceutical companies; teachers, scientific researchers, and graduate students in domestic and foreign medical schools; scientific and technological management cadres and medical intelligence personnel related to pharmacy and pharmaceuticals, etc.