舒更葡糖钠的合成工艺优化  

Improved Synthetic Process of Sugammadex Sodium

作　　者：彭祥龙 鲍广龙 张乃华 陈成富 张贵民 PENG Xianglong;BAO Guanglong;ZHANG Naihua;CHEN Chengfu;ZHANG Guimin(National Engineering and Technology' Research Center of Chirality Pharmaceutical. L unan Pharmaceutical Group Co., Ltd, Linyi 273400)

机构地区：[1]鲁南制药集团股份有限公司国家手性制药工程技术研究中心

出　　处：《中国医药工业杂志》2019年第5期511-513,共3页Chinese Journal of Pharmaceuticals

摘　　要：本研究对舒更葡糖钠的合成方法进行改进。以γ-环糊精为起始物料,经对甲苯磺酰氯酰化得6-全脱氧-6-全对甲苯磺酸酯-γ-环糊精( 3)。该法避免了溴素及五氯化磷的使用,克服了合成卤代烃中间体时产生三苯氧膦和磷酰化杂质的缺点;并且该反应条件温和,只需通过简单的重结晶操作即可得纯度合格的中间体。然后3 与3-巯基丙酸在氢氧化钠条件下经取代反应制得目标产品。终产物用乙醇-水纯化,加入质量比20%的活性炭,使其纯度由98%提高至99.5%,最大单杂小于0.1%。该法革除了柱色谱、透析方法等的使用,反应条件温和、操作简便、纯度高,总收率72.8%。The synthetic method of sugammadex sodium was improved.γ-Cyclodextrin reacted with tosyl chloride to give octakis(6-deoxy-6-tosylate)-γ-cyclodextrin (3). This method can avoid the use of bromine and phosphorus pentachloride, overcome the defects of producing triphenylphosphine oxide and phosphorylation impurities in the synthesis of halohydrocarbon intermediates. Then the target compound was obtained via substitution of 3 and 3-mercaptopropionic acid in the presence of sodium hydroxide. The purity was increased from 98% to 99.5% by recrystallization with EtOH-H2O, adding 20% of activated carbon, and the maximum impurity was less than 0.1%. This method, without column chromatography or dialysis, has mild reaction conditions, simple operation and high purity with a total yield of 72.8%.

关 键 词：舒更葡糖钠 肌松药逆转剂 Γ-环糊精 工艺改进 

分 类 号：R971[医药卫生—药品] R914.5[医药卫生—药学]