一种用于制备生物碱的实用手性砌块的百克级合成方法  

A practical and hectogram-scale preparation of a chiral building block for alkaloid synthesis

作　　者：何欢 汪小蓓[1] 宋颢[1] HE Huan;WANG Xiaobei;SONG Hao(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院

出　　处：《华西药学杂志》2019年第3期207-210,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:21732005、21572140)

摘　　要：目的设计并合成一种大规模用于制备生物碱的实用手性砌块。方法在有机催化条件下,叔丁基甲基马来酸酯与邻硝基肉桂醛发生不对称Michael加成,随后酸水解脱羧。结果与结论经3步反应(总收率50%)以百克级的规模制备得到手性砌块Ⅰ(96%ee)。OBJECTIVE To design and synthesize a chiral building block for alkaloids practically used in large scale.METHODS The tert-butyl methyl malonate reacted with o-nitrocinnamic aldehyde via asymmetric organocatalytic Michael addition,followed by a two-step one-pot decarboxylation.RESULTS and CONCLUSION The chiral building blockⅠ(96%ee)has been obtained over three steps(50%yield)in hectogram scales.

关 键 词：手性砌块 百克级 有机催化 不对称MICHAEL加成 一锅法脱羧 γ-羰基酯 邻硝基肉桂醛 叔丁基甲基马来酸酯 

分 类 号：R914[医药卫生—药物化学]