双荧光素位点选择性修饰的α-环糊精合成  

Synthesis of Site-Selectively Modifiedα-Cyclodextrin with Bifluorescein

作　　者：任蒙蒙 张诗茗 邹晶 袁兰 王天宇 贾彦兴 韩鸿宾[1,4] REN Meng-meng;ZHANG Shi-ming;ZOU Jing;YUAN Lan;WANG Tian-yu;JIA Yanxing;HAN Hong-bin(Institute of Medical Technology,Peking University Health Science Center,Beijing 100191,China;Department of Chemical Biology,Peking University School of Pharmaceutical Sciences,Beijing 100191,China;Peking University Medical and Health Analysis Center,Beijing 100191,China;Department of Radiology,Peking University Third Hospital,Beijing 100191,China;Department of Medicinal Chemistry,Peking University School of Pharmaceutical Sciences,Beijing 100191,China)

机构地区：[1]北京大学医学技术研究院,北京100191 [2]北京大学药学院化学生物学系,北京100191 [3]北京大学医药卫生分析中心,北京100191 [4]北京大学第三医院放射科,北京100191 [5]北京大学药学院药物化学系,北京100191

出　　处：《中国药学杂志》2023年第2期160-164,共5页Chinese Pharmaceutical Journal

基　　金：国家自然基金仪器专项资助(61827808)。

摘　　要：目的设计合成双荧光素修饰的6^(A),6^(D)-双脱氧-α-环糊精。方法从α-环糊精出发,经过苄基化保护得到过苄基化-α-环糊精(1),特定温度下利用DIBAL-H对过苄基化-α-环糊精进行选择性脱保护,得到中间体2,中间体2经磺酰化、叠氮化后将6^(A),6^(D)位点上伯醇转化为叠氮,再经氢化铝锂还原为伯胺。再在钯碳/氢气条件脱除苄基保护,获得6^(A),6^(D)-双脱氧-6^(A),6^(D)-二氨基-α-环糊精(6)。碱性条件下,中间体6与两倍当量的异硫氰基荧光素发生亲核加成反应,得到6^(A),6^(D)-双脱氧-6^(A),6^(D)-双荧光素-α-环糊精(7)。结果6个中间体和1个目标产物的结构经过核磁共振氢谱和质谱确证。结论成功设计合成双荧光素修饰的6^(A),6^(D)-双脱氧-α-环糊精(7),并且获得新的环糊精衍生物6^(A),6^(D)-氧-对甲苯磺酰基-2^(A-F),3^(A-F),6^(B),6^(C),6^(E),6^(F)-十六氧苄基-α-环糊精(3)。OBJECTIVE Design and synthesis of 6^(A),6^(D)-dideoxy-6^(A),6^(D)-bifluorescein-α-cyclodextrin.METHODS Perbenzylated-α-cyclodextrin(1)is obtained through benzylation protection ofα-cyclodextrin,and the perbenzylated-α-cyclodextrin(1)is then selectively de-O-alkylated by DIBAL-H at a specific temperature,so that the intermediate 2 is obtained.After being sulfonylated,azided,primary alcohol of intermediate 2 on 6^(A),6^(D)site is converted into azide group,and then reduced to primary amine through lithium aluminum hydride.Under the condition of palladium carbon/hydrogen,the benzyl protection was removed to afford 6^(A),6^(D)-dideoxy-6^(A),6^(D)-diamino-α-cyclodextrin(6).Under alkaline condition,intermediate 6 undergoes a nucleophilic addition reaction with twice the equivalent amount of isothiocyanofluorescein to give 6^(A),6^(D)-dideoxy-6^(A),6^(D)-difluorescein-α-cyclodextrin(7).RESULTS The structures of 6 intermediates and 1 target product were confirmed by~1H-NMR and MS.CONCLUSION Successfully designed and synthesized double fluorescein-modified 6^(A),6^(D)-deoxy-α-cyclodextrin(7),and obtained a new intermediate compound 6^(A),6^(D)-oxy-p-toluenesulfonyl-2^(A-F),3^(A-F),6^(B),6^(C),6^(E),6^(F)-hexadecyloxybenzyl-α-cyclodextrin(3).

关 键 词：Α-环糊精 荧光素 荧光素修饰 荧光探针 

分 类 号：R944[医药卫生—药剂学]