Design and Synthesis of Glycosylated Aromatic Nitrogen Mustard Derivatives  

作　　者：LIU Tie-mei WANG Shu-sheng ZHU Guang-ze LI Ming-yang ZHANG Li-ping 

机构地区：[1]School of Life Sciences, Northeast Normal University, Changchun 130024, P. R. China [2]China-Japan Union Hospital, Jilin Universty, Changchun 130033, P. R. China [3]School of Life Science, Anhui University, Hefei 230039, P. R. China [4]College of Traditional Chingese Medicine in Changchun, Changchun 130021, P. R. China

出　　处：《Chemical Research in Chinese Universities》2007年第3期300-302,共3页高等学校化学研究（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No20030708);the Natural Science Foundation of JinlinProrince, P R China(No20050702-4)

摘　　要：Antibody-directed enzyme prodrug therapy（ADEPT） is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol （ glycosyl donors） to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.Antibody-directed enzyme prodrug therapy（ADEPT） is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol （ glycosyl donors） to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.

关 键 词：GLYCOSYLATION Nitrogen mustard derivative PRODRUG ADEPT 

分 类 号：R914.5[医药卫生—药物化学] R979.1[医药卫生—药学]