Design,synthesis and preliminary bio-evaluation of glucose-cholesterol derivatives as ligands for brain targeting liposomes  

作　　者：Fan Lei Wei Fan Xian Kun Li Shan Wang Li Hai Yong Wu 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

出　　处：《Chinese Chemical Letters》2011年第7期831-834,共4页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81072532)

摘　　要：A series of glucose-cholesterol derivatives 8a-8e as ligands for brain targeting liposomes were synthesized. The preparation of compound 6 involved temporary protection of glucose with chlorotrimethylsilicane and hexamethyldisilazane followed by selectively hydrolyzed. The known cholesteryl tosylate 1 were coupled to ethylene glycols to afford alcohol 2a-2e. Substitution and deprotection of alcohol 2a-2e furnished the acids 4a-4e, which was condensed with compound 6 to get compounds 7a-7e, and then was deprotected in tetrahydrofuran with TFA to obtain the title compounds. As a model drug, tegafur was entrapped by liposomes coupled with 8b, and preliminary in vivo evaluation shown 8b could enhance the ability of liposomes delivering tegafur across the blood brain barrier.A series of glucose-cholesterol derivatives 8a-8e as ligands for brain targeting liposomes were synthesized. The preparation of compound 6 involved temporary protection of glucose with chlorotrimethylsilicane and hexamethyldisilazane followed by selectively hydrolyzed. The known cholesteryl tosylate 1 were coupled to ethylene glycols to afford alcohol 2a-2e. Substitution and deprotection of alcohol 2a-2e furnished the acids 4a-4e, which was condensed with compound 6 to get compounds 7a-7e, and then was deprotected in tetrahydrofuran with TFA to obtain the title compounds. As a model drug, tegafur was entrapped by liposomes coupled with 8b, and preliminary in vivo evaluation shown 8b could enhance the ability of liposomes delivering tegafur across the blood brain barrier.

关 键 词：Liposome ligands Brain target GLUTt transporter TEGAFUR SYNTHESIS 

分 类 号：TQ460.6[化学工程—制药化工] Q78[生物学—分子生物学]