氰基硼氢化钠还原胺化京尼平合成拟生物碱与活性  

Reductive Amination of Genipin with NaBH_(3)CN to Synthesize Alkaloid-likes and Bioactivity

作　　者：秦杰琛 曾小娟 张韶湘 张晓梅 刘鑫洋 邹澄 赵庆 QIN Jie-chen;ZENG Xiao-juan;ZHANG Shao-xiang;ZHANG Xiao-mei;LIU Xin-yang;ZOU Cheng;ZHAO Qing(School of Pharmaceutical Science&Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,Kunming Yunnan 650500;Faculty of Pharmacy,Yunnan University of Chinese Medicine,Kunming Yunnan 650500,China)

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500 [2]云南中医药大学中药学院,云南昆明650500

出　　处：《昆明医科大学学报》2021年第2期18-22,共5页Journal of Kunming Medical University

基　　金：国家自然科学基金资助项目(81460533,81060262);云南省科技厅-云南中医药大学应用基础研究联合专项基金资助项目[2017FF116(-011)]。

摘　　要：目的以京尼平苷为原料通过还原胺化反应合成拟生物碱的方法。方法京尼平与胺类化合物在氰基硼氢化钠存在下进行还原反应:京尼平与芳基乙胺的甲醇溶液混合后,加入过量氰基硼氢化钠,放置室温下反应3d,产物经石油醚-异丙醇-二乙胺,石油醚-乙酸乙酯等洗脱分离。结果合成共得到9个拟生物碱并对部分拟生物碱进行活性筛选,找到治疗Ⅱ型糖尿病的PTP1B抑制剂。结论部分受试化合物对PTP1B有抑制作用。一系列活性衍生物的获得为化合物结构及其生物活性间的构效关系研究打下了基础,有利于寻找具有更高活性的PTP1B抑制剂。Objective To explore a method for the synthesis of alkaloid-likes from Genipin by reductive amination is reported.Methods The reduction of Genipin and amines in the presence of sodium cyanoborohydride:after the methanol solution of Genipin and arylethylamine was mixed,excessive sodium cyanoborohydride was added and the reaction was kept at room temperature for 3 days.The product was eluted and separated on silica gel by petroleum ether-isopropyl alcohol-diethylamine and petroleum ether-ethyl acetate.Results Nine alkaloid-likes were synthesized.Some alkaloid-likes were screened for inhibition activity of PTP1B enzyme forⅡdiabetes treatment.Conclusions All of the tested compounds have a certain inhibitory effect on PTP1B.The acquisition of a series of active derivatives has laid a foundation for the study of the structure-activity relationship between the compounds and their bioactivities,so as to facilitate the search for more active PTP1B inhibitors.

关 键 词：京尼平 拟生物碱 还原胺化 抗PTP1B活性 

分 类 号：R284.1[医药卫生—中药学]