2-磺酸-4-硫代丁酸类抗体-药物偶联物连接子的合成  

Synthesis of 2-sulfonic acid-4-thiobutanoic acid antibody-drug conjugate linker

作　　者：杨丽萍 曹小冬 YANG Liping;CAO Xiaodong(School of Science,Zhejiang Sci-Tech University,Hangzhou 310018,China)

机构地区：[1]浙江理工大学理学院,杭州310018

出　　处：《浙江理工大学学报（自然科学版）》2023年第3期374-378,共5页Journal of Zhejiang Sci-Tech University(Natural Sciences)

摘　　要：设计并合成成本低廉但功能相近的Sulfo-SPDB类似物2-磺酸基-4-(三甲苯基硫代)丁酸,以降低抗体-药物偶联物(Antibody-drug conjugate, ADC)亲水性连接子2-磺酸基-4-(2-吡啶二硫代)丁酸(Sulfo-SPDB)的制备成本。以4-巯基丁酸为起始原料,通过取代、磺酰化、还原、巯基保护等四个步骤制得Sulfo-SPDB类似物。通过优化反应条件,目标产物的总产率可达85%;采用质谱、紫外、^(1)H-NMR对产物的结构进行表征和分析,结果显示产物确为目标产物。该合成路线具有原料易得、反应条件温和、操作简便、能耗低等特点,对Sulfo-SPDB衍生物的合成具有借鉴意义。In order to reduce the preparation cost of antibody-drug conjugate(ADC)hydrophilic linker 2-sulfo-4-(2-pyridinyldithio)-butanoic acid(Sulfo-SPDB),we designed and synthesized the Sulfo-SPDB analogue 2-sulfo-4-trytylthio-butanoic acid with the characteristics of lower cost and similar function.The synthesis started from 4-mercaptobutyric acid,and went through substitution,sulfonylation,reduction,and then protection reaction.By optimizing the reaction conditions,the Sulfo-SPDB analogue was prepared in four steps with a total yield of 85%.The structure of the product was characterized by mass spectrometry,ultraviolet and ^(1)H-NMR.The results show that the product is the target product.The synthetic route has the characteristics of few synthetic steps,mild reaction conditions,simple operation,

关 键 词：抗体-药物偶联物 连接子 2-磺酸基-4-(2-吡啶二硫代)丁酸 2-磺酸基-4-(三甲苯基硫代)丁酸 巯基保护 磺酰化 

分 类 号：O622.6[理学—有机化学]