Scalable synthesis of salidroside  

具可放大性的红景天苷合成工艺研究(英文)

作　　者：梁清照 李辉[1,2] 张文轩[1,2] 孟祥豹[1,2] 李中军[1,2] 

机构地区：[1]北京大学医学部天然药物及仿生药物国家重点实验室 [2]药学院化学生物学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2014年第7期446-453,共8页中国药学（英文版）

基　　金：the National Basic Research Program of China(973 Program,Grant No.2012CB822100);the National Key Technology R&D Program"New Drug Innovation"of China(Grant No.2012ZX09502001-001);the National Natural Science Foundation of China(Grant No.21232002,21072016 and 21072017)

摘　　要：By analyzing the key steps that restricted the industrial synthesis of salidroside, selective protection of tyrosol with different acylation reagents was adopted. The strategy facilitated the crystallization of intermediates, which allowed the scalable synthesis of salidroside. It included a reaction of penta-O-acetyl-β-D-glucose with acyl protected tyrosol in the presence of Lewis acid catalyst（ZnCl2）, followed by deacylation under basic condition（NaOMe/MeOH） to give the salidroside. The total yield of this three-step reaction was 47%. Final product and intermediates were purified by recrystallization, which significantly reduced the cost and made the large scale synthesis feasible.通过分析现有红景天苷化学合成方法的优缺点,分析制约现有工艺可放大性的关键因素,采用通过优化酪醇酚羟基酰基保护基的类型实现关键中间体结晶性的策略,探索发展出了具可放大性的红景天苷合成新工艺:以无水ZnCl2为催化剂,高活性、价廉易得的β-D-五乙酰葡萄糖为供体,苯甲酰基保护酚羟基酪醇为受体进行苷化反应,以MeONa/MeOH脱保护得到红景天苷。新工艺共三步反应,总收率47%;路线涉及的中间体均可通过重结晶进行纯化,革除了柱层析操作,显著降低了生产成本,具备可放大性。

关 键 词：SALIDROSIDE Acylation of tyrosol CRYSTALLIZATION Scale up feasibility Synthesis 

分 类 号：R284.3[医药卫生—中药学]