N-正丁基-1-脱氧野尻霉素合成方法的改进  

An improved strategy to synthesize N-butyl-1-deoxynojirimycin

作　　者：王佳佳[1,2] 张振兴[1] 李铁海[1] 郭利娜[1] 刘艳坤[3,2] 赵炜[1] 

机构地区：[1]南开大学药学院,天津300071 [2]天津市国际生物医药联合研究院,天津300071 [3]南开大学生命科学学院,天津300071

出　　处：《中国药物化学杂志》2011年第4期298-303,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(20802037);国家重点基础研究发展计划项目(973项目;2007CB914403)

摘　　要：目的改进N-正丁基-1-脱氧野尻霉素的合成方法。方法该文通过酰化反应分别用丁酰氯和丁酸酐将丁酰基引入到2,3,4,6四-苄基葡萄糖内酰胺的氮原子上,然后用氢化铝锂将两个羰基还原,得到N-正丁基-2,3,4,6四-苄基-1脱-氧野尻霉素。结果与结论该方法在改进部分将收率提高为相关文献的2～3倍,在氨解开环这一步,尝试用正丁基胺代替饱和氨气的甲醇溶液,并对其关环产物以及副产物的生成机制进行了探讨。As an amino sugar derivative,N-butyl-1-deoxynojirimycin has promising therapeutics in treatment of diabetes,viral infections,metastatic cancers and Gancher′s diseases.Low yield is the main obstacle for chemical synthetic of N-butyl-1-deoxynojirimycin.To improve the synthetic procedure,butyryl group was introduced to the nitrogen atom of 2,3,4,6-tetra-O-benzyl-D-gluconolactam（5） using butyryl chloride or buty-ric anhydride,respectively.The resulting compound N-butyryl-2,3,4,6-tetra-O-benzyl-D-gluconolactam（6） was treated with aluminium hydride to afford N-butyl-2,3,4,6-tetra-O-benzyl-deoxynojirimycin（7） in a satisfying yield.Compared with the previously reported synthetic strategy（yield of 23.4%）,the developed method can significantly increase the yield（54%） from compound 5 to 7.In summary,we have successfully optimised the synthetic procedures of N-butyl-1-deoxynojirimycin.Besides,instead of methanolic ammonia,n-butylamine was used for ammonolysis,expected product and possible mechanism of forming the byproduct were discussed in the ring-close step.

关 键 词：N-正丁基-1脱-氧野尻霉素 合成 工艺改进 

分 类 号：R914[医药卫生—药物化学]