Facile preparation and characterization of novel oleanane-type triterpene functionalized β-cyclodextrin conjugates  

作　　者：Pingxuan Jiao Shouxin Wang Shuobin Liang Man Li Qianqian Gao Dezhong Ji Yingying Chen Haiwei Li Fuxiang Ran Yongmin Zhang Lihe Zhang Demin Zhou Sulong Xiao 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University [2]School of Pharmacy, Jining Medical University [3]Sorbonne Universite, Institut Parisien de Chimie Moleculaire, CNRS UMR 8232 [4]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences

出　　处：《Chinese Chemical Letters》2019年第3期690-693,共4页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Nos. 81573269, 21572015, 21877007, 91753202 and 21702007);and the open funding of the State Key Laboratory of Phytochemistry and Plant Resources in West China

摘　　要：Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.

关 键 词：Β-CYCLODEXTRIN DIBAL-H Oleanolic ACID Echinocystic ACID Synthesis 

分 类 号：TQ460.1[化学工程—制药化工]