基于2-(4-二羟基硼烷)苯基喹啉-4-羧酸的二硼酸化合物的合成  

Synthesis of bisboronic acid derivatives base on 2-(4-boronophenyl) quinoline-4-carboxylic acid

作　　者：王凯[1,2,3,4] 张浩超 孙敬勇[1,2,3,4] 姚庆强[1,2,3,4] 吴忠玉[1,2,3,4] 

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,山东济南250200 [2]山东省医学科学院药物研究所,山东济南250062 [3]国家卫生部生物技术药物重点实验室,山东济南250062 [4]山东省罕少见病重点实验室,山东济南250062

出　　处：《化学研究》2017年第2期185-190,共6页Chemical Research

基　　金：山东省自然科学基金资助项目(ZR2014YL035);2014年度留学人员科技活动项目择优资助项目;济南大学教研项目(J1447);山东省医学科学院医药卫生科技创新工程

摘　　要：以4-溴苯乙酮、靛红及常见试剂为起始原料,通过Pfitzinger reaction、羧基酯化、钯催化、水解等反应合成2-(4-二羟基硼烷)苯基喹啉-4-羧酸(PBAQA).二胺化合物经二碳酸二叔丁酯单保护、酰胺缩合、盐酸脱保护基,再与另一端苯基硼酸化合物酰胺缩合,合成了3个含有PBAQA结构的二硼酸新化合物,考察了溶剂选择、反应温度、活化反应时间以及反应中羧基化合物与1,3-二环己基碳化二亚胺(DCC)和1-羟基苯并三唑(HOBT)物质的量之比对二硼酸类化合物收率的影响.通过IR、~1H NMR、^(13)C NMR、HRMS对新化合物的结构进行表征.结果表明最佳反应条件为以N,N-二甲基甲酰胺(DMF)作溶剂,反应温度20℃,活化反应60 min,反应中羧基化合物与DCC和HOBT的物质的量之比在1∶20∶20的条件下,收率可达82%,纯度90%.该合成路线具有操作步骤简便,经济适用,副产物少易于纯化等特点,对二硼酸化合物衍生化研究具有重要实用和经济价值.2-（4-boronophenyl）quinoline-4-carboxylic acid （PBAQA） was synthesized by the Pfitz- inger reaction, carboxyl esterification, Pd-catalyzed reaction and hydrolysis reaction, using 1-（4-bro- mophenyl）ethanone and isatin as the major starting materials. Three PBAQA bisboronic acid com- pounds were synthesized through monoprotection of the diamine compounds by tert-butyl ester carbon- ate, amide condensation reaction, deprotection by hydrochloric acid and amide condensation with an- other phenyl boronic acid. The effect of solvent, reaction temperature, mole ratio of carboxyl com- pound, N, N＇-dicyclohexylcarbodiimide （DCC） and NHydroxybenzotrizole （ HOBT）, the activation time on the yield of bisboronic acid compounds were investigated. All novel compounds were character- ized by IR, NMR, HRMS, etc. The optimized experimental conditions were as follows： 20 ℃ of reac- tion temperature 60 minubes of reaction time and 1/20 of mole ratio of carboxyl compound, DCC and HOBT in the solvent of N, N＇-dimethyl formamide （DMF）. Under the optimized conditions, the yield of bisboronic acid compounds was up to 82% and the purity was 90%. This synthetic route has many advantages, such as low cost, less by-products, easy purification and high yields.

关 键 词：硼酸类化合物 儿茶酚 荧光探针 合成 

分 类 号：O627[理学—有机化学]