紫杉醇生物素标记衍生物的合成  

Synthesis of Biotinylated Paclitaxel

作　　者：巩凯[1] 陈洁[1] 唐汝培[1,2] 陈敬华[1] 

机构地区：[1]江南大学药学院,江苏无锡214122 [2]安徽大学生命科学学院,安徽合肥230601

出　　处：《化学试剂》2015年第5期457-459,480,共4页Chemical Reagents

基　　金：国家自然科学基金资助项目(51303069)

摘　　要：以生物素、紫杉醇和6-氨基己酸为原料,经酰化、水解、酯化反应等步骤合成具有长臂连接的标题化合物。在三乙胺催化下,生物素与N-羟基琥珀酰亚胺反应生成N-羟基琥珀酰亚胺生物素酯。在氯化亚砜、甲醇反应体系下,由6-氨基己酸合成6-氨基己酸甲酯。在三乙胺作用下,N-羟基琥珀酰亚胺生物素酯和6-氨基己酸甲酯反应生成生物素-氨基己酸甲酯;生物素-氨基己酸甲酯在Li OH·H2O作用下,水解反应得到6-生物素氨基己酸。以DMF为溶剂,在N,N'-二环己基碳二亚胺(DCC)、4-二甲氨基吡啶(DMAP)作用下,6-生物素氨基己酸与紫杉醇反应,生成标题化合物。标题化合物和重要中间体化合物采用IR、1HNMR、MS进行了表征。A biotinylated paclitaxel with an extra-long chain spacer arm was synthesized via acylation reaction,hydrolysis reaction,esterification reaction steps from biotin,paclitaxel,and 6-aminohexanoic acid. The reaction of d-biotin with N-hydroxysuccinimide resulted in d-biotin N-succinimidyl ester catalyzed by triethylamine. Methyl 6-aminohexanoate was synthesized in thionyl chloride and CH3 OH media. The reaction of d-biotin N-succinimidyl ester with methyl 6-aminohexanoate resulted in N-biotin methyl-6-aminohexanoate catalyzed by triethylamine. 6-Biotinamidohexanoic acid was prepared by the hydrolysis reaction of biotin-methyl-6-aminohexanoate under Li OH·H2O. With N,N＇-dicyclohexylcarbodiimide（ DCC） and 4-dimethylaminopyridine（ DMAP）,the reaction of 6-biotinamidohexanoic acid and paclitaxel resulted in the target compound. The structures were confirmed using IR,1HNMR and MS.

关 键 词：紫杉醇 生物素 标记物 合成 

分 类 号：O626.3[理学—有机化学]