新型马蹄金素三触角半乳糖苷衍生物的合成及其抗乙肝病毒活性  

Synthesis and Anti-HBV Activities of MTS Derivatives of Novel Triantennary Cluster Galactoside

作　　者：周晨[1,2,3] 徐广灿 胡占兴[2,3] 曾晓萍 刘青川 袁洁[5] 黄正明[4] 梁光义[1,2,3] 徐必学[2,3] ZHOU Chen;XU Guang-can;HU Zhan-xing;ZENG Xiao-ping;LIU Qing-chuan;YUAN Jie;HUANG Zheng-ming;LIANG Guang-yi;XU Bi-xue(Guiyang College of Traditional Chinese Medicine,Guiyang 550002,China;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang 550014,China;302 Hospital of PLA,Beijing 100039,China;Houbo College,Xinjiang Medical University,Karamay 834000,China)

机构地区：[1]贵阳中医学院,贵州贵阳550002 [2]贵州医科大学省部共建药用植物功效与利用国家重点实验室,贵州贵阳550014 [3]贵州省中国科学院天然产物化学重点实验室,贵州贵阳550014 [4]中国人民解放军第三○二医院,北京100039 [5]新疆医科大学厚博学院,新疆克拉玛依834000

出　　处：《合成化学》2018年第3期160-167,共8页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(81360472);西部之光人才项目(2014年);黔人项目资助合同(2014)7号

摘　　要：以三羟甲基氨基甲烷为原料,经4步反应制得含有三触角糖基和链接臂的关键中间体N-(4-N-Boc-氨基-丁酰基)-三-[O-(2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基)-羟甲基]-甲氨(5);5脱除Boc保护后分别与含有羧基的马蹄金素衍生物(7a^7c)在氯甲酸异丁酯(IBCF)/N-甲基吗啉(NMM)作用下缩合,随后在甲醇钠催化下脱除乙酰基合成了3个具有潜在肝靶向的三触角糖簇马蹄金素衍生物(9a^9c),其结构经~1H NMR,13C NMR,~1H-~1H COSY,HMQC和MS(ESI)表征。并通过HepG2 2.2.15细胞模型初步评价了其抗乙肝病毒(HBV)活性。结果表明:9a^9c均抑制HBV DNA的复制,且存在一定的量效关系。A key intermediate containing of triantennary glycans and a linker,N-(4-N-Boc-amino-butyryl)-tris-[O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-hydroxymethyl]-methylamine(5),was synthesized through a four step raction by using tris(hydroxymethyl)aminomethane as starting material.The deprotection of Boc group of compound 5 gave the corresponding amine compound which was reacted with carboxyl-containing MTS derivatives(7a^7c)respectively in the present of IBCF/NMM and followed by deprotection of acetyl group catalyzed by sodium methoxide to provide three triantennary cluster galactosides of MTS with potential for hepatic targeting(9a^9c).The structures were confirmed by 1 H NMR,13 C NMR,1 H-1 H COSY,HMQC and MS(ESI).The anti-HBV activities of those compounds were evaluated in HepG2 2.2.15 cells.The screening results showed that all target compounds had inhibitory effect on HBV DNA replication in HepG2 2.2.15 cells in a dose-response manner.

关 键 词：糖簇效应 三触角半乳糖苷 马蹄金素衍生物 合成 抗HBV活性 

分 类 号：O625.6[理学—有机化学]