磷酸奥司他韦关键起始原料的非对映异构体合成  

Synthesis of the Diastereomer of Oseltamivir Phosphate Key Starting Material

作　　者：陈德宝 盛荣[1] CHEN Debao;SHENG Rong(College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058)

机构地区：[1]浙江大学药学院,浙江杭州310058

出　　处：《中国医药工业杂志》2022年第9期1274-1278,共5页Chinese Journal of Pharmaceuticals

摘　　要：(1R,5S,6S)-5-(戊烷-3-基氧基)-7-氧杂双环[4.1.0]庚-3-烯-3-羧酸乙酯(2)是合成磷酸奥司他韦(1)的关键起始原料。该研究以莽草酸为原料,经酯化、3-戊酮叉保护、苯甲酰基保护、缩酮还原开环、甲磺酰基保护、碱处理等6步反应合成了2的(1R,5R,6R)-型非对映异构体3,为评估关键起始原料2和原料药1的手性纯度提供对照。目标物经^(1)H NMR、^(13)C NMR和ESI-MS等确证结构。Ethyl(1R,5S,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate(2)was the key starting material of oseltamivir phosphate(1).Compound 3,the(1R,5R,6R)-diastereomer of 2,was synthesized as the standard control to evaluate the chiral purity of 2 as well as 1.With shikimic acid as starting material,compound 3 was obtained through esterification,3-pentanone protection,5-hydroxybenzylation,reductive ring opening of the ketals,4-hydroxymethylsulfonylation,and alkalic hydrolysis.The structure was conformed by ^(1)H NMR,^(13) C NMR and ESI-MS.

关 键 词：磷酸奥司他韦 关键起始原料 非对映异构体 有关物质 合成 

分 类 号：R914.5[医药卫生—药物化学]