新型Bluco类β-内酰胺酶分子探针的合成

Synthesis of New β-Lactamase Molecular Probe Bluco Analogues

以2-氰基-6-羟基苯并噻唑为原料,与溴乙醛缩二乙醇缩合制得缩醛后再水解合成中间体6-(2-羰乙基)苯并[d]噻唑-2-甲腈(2);7-苯乙酰氨基-3-氯甲基头孢菌烷酸二苯甲酯依次经碘代和Wittig反应得(Z)-3-[3-(2-氰基苯并[d]噻唑-6-氧)丙-1-烯]-8-羰基-7-(2-苯乙酰氨基)-5-噻-1-氮[4.2.0]辛-2-烯-2-甲酸二苯甲酯(5);5经脱保护、缩合和氧化反应合成了3个新的Bluco类似物,其结构经1H NMR,13C NMR和HR-MS(ESI)表征。

6-（2-Oxoethoxy） benzo[d]thiazole-2-carbonitrile（2） was prepared by condensation of 2-cyano-6-hydroxy benzothiazole（1） and 2-bromo-1,1-diethoxyethane and then hydrolytic reaction.（6R,7R,Z）-benzhydryl 7-benzamido-3-[3-（2-cyanobenzo[d]thiazol-6-yloxy） prop-1-enyl]-8-oxo-5-thia-1-aza-bicyclo[4. 2. 0]oct-2-ene-2-carboxylate（5） was synthesized by iodination and Wittig reaction from（6R,7R）-benzhydryl 7-benzamido-3-（chloromethyl）-8-oxo-5-thia-1-aza-bicyclo [4. 2. 0]oct-2-ene-2-carboxylate. Three novel analogues of Bluco were synthesized by deprotection,condensation and oxidation reactions from 5. The structures were characterized by1 H NMR,13 C NMR and HR-MS（ESI）.