盐酸纳曲酮有关物质的合成  

Synthesis of Related Substances of Naltrexone Hydrochloride

作　　者：权睿杰 丁泽洲 张福利[1] 张涛[1] QUAN Ruijie;DING Zezhou;ZHANG Fuli;ZHANG Tao(Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,China State Institute of Pharmaceutical Industry Co.,Ltd.,Shanghai 201203;School of Chemistry and Chemical Engineering,Shanghai University of Engineering Science,Shanghai 201620)

机构地区：[1]中国医药工业研究总院有限公司,上海医药工业研究院有限公司,上海201203 [2]上海工程技术大学化学化工学院,上海201620

出　　处：《中国医药工业杂志》2023年第12期1718-1723,共6页Chinese Journal of Pharmaceuticals

摘　　要：为了有效控制盐酸纳曲酮的质量,该研究合成了7个有关物质:17-(1-丁烯基)-4,5-环氧-3,14-二羟基吗啡烷-6-酮(有关物质C)、双纳曲酮(有关物质D)、3-环丙甲氧基-17-(环丙甲基)-4,5-环氧-14-羟基吗啡烷-6-酮(有关物质E)、17-正丁基-4,5-环氧-3,14-二羟基吗啡烷-6-酮(有关物质H)、17-(环丙甲基)-3-甲氧基-4,5-环氧-14-羟基吗啡烷-6-酮(有关物质J)、17-(环丙甲基)-4,5-环氧-3,14-二羟基吗啡-7-烯-6-酮(有关物质K)、纳曲酮氮氧化物(有关物质L)。其中,有关物质K、L未收录进《欧洲药典》10.0中,有关物质C、D、H的合成路线未见文献报道。上述有关物质结构均经MS、1H NMR、13C NMR确证。In order to effectively control the quality of naltrexone hydrochloride,seven related substances were synthesized in this study:17-(1-butenyl)-4,5-epoxy-3,14-dihydroxymorphine-6-one(related substance C),bis-naltrexone(related substance D),3-cyclopropylmethoxy-17-(cyclopropylmethyl)-4,5-epoxy-14-hydroxymorphine-6-one(related substance E),17-n-butyl-4,5-epoxy-3,14-dihydroxymorphine-6-one(related substance H),17-(cyclopropylmethyl)-3-methoxyl-4,5-epoxy-14-hydroxymorphine-6-one(related substance J),17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphin-7-ene-6-one(related substance K),naltrexone nitrogen oxide(related substance L).The related substances K and L were not included in European pharmacopoeia 10.0.The synthetic routes of substances C,D and H had not been reported.The structures of these compounds were confirmed by MS,1H NMR and 13C NMR.

关 键 词：纳曲酮 有关物质 合成 质量控制 

分 类 号：R914[医药卫生—药物化学] TQ460.6[医药卫生—药学]