氯化两面针碱合成工艺优化  

Optimization of Synthetic Process of Nitidine Chloride

作　　者：谭善伦 臧成旭 代黎[2] 黄景华 张大志[1,2] 

机构地区：[1]福建中医药大学药学院,福建福州350108 [2]第二军医大学药学院有机化学教研室,上海200433 [3]上海捌加壹医药科技有限公司,上海200433

出　　处：《中国医药工业杂志》2015年第2期123-126,共4页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金(21272270;21072226)

摘　　要：4-(苯并[d][1,3]二氧戊环-5-基)-2-(3,4-二甲氧基苯基)-4-氧代丁腈经水解、还原反应得4-(苯并[d][1,3]-二氧戊环-5-基)-2-(3,4-二甲氧基苯基)丁酸;再经傅克反应、刘卡特反应、环合得2,3-亚甲二氧基-8,9-二甲氧基-4b,10b,11,12-四氢苯并[5,6-c]菲啶;最终通过芳构化、硫酸二甲酯甲基化并经氯化钠盐交换得氯化两面针碱。优化后工艺总收率为2.5%,操作简便,反应条件温和,原料和试剂经济易得。Nitidine chloride was synthesized from 4-（benzo [d] [1,3] dioxol-5-yl）-2-（3,4-dimethoxyphenyl）-4- oxobutanenitrile via hydrolysis and reduction to give 4-（benzo[ 1,3] dioxol-5-y1）-2-（3,4-dimethoxyphenyl）butanoic acid, subsequent Friedel-Crafts cyclization, Leuckart reaction, and cyclization to obtain 2,3-methylenedioxy-8,9-dimethoxy- 4b,10b, 11,12-tetrahydrobenzo [5,6-c] phenanthridine, which was subjected to aromatization with Pd/C, followed by methylation with dimethyl sulfate and salt exchange with sodium chloride. The total yield was 2.5 % in the optimized process, all the reaction conditions were mild, and the reagents were cheap and commercial available.

关 键 词：氯化两面针碱 合成 优化 

分 类 号：R284.3[医药卫生—中药学]