双酰亚胺类蛋白质荧光探针的合成

Synthesis of Di-imides as Protein Fluorescent Probes

以6种N 取代 4 氨基 邻苯二甲酰亚胺及马来酸酐为起始原料合成了相应的6种N (N 取代 邻苯二甲酰亚胺 4 基) 马来酰亚胺(Ⅱ)。丙酮为溶剂,氮气保护,室温下N 取代 4 氨基 邻苯二甲酰亚胺及马来酸酐反应2 5h得到N (N 取代 邻苯二甲酰亚胺 4 基) 氨基马来酰酸(Ⅰ),收率均>90%。Ⅰ在三乙胺与乙酐作用下,脱水环合生成N (N 取代 邻苯二甲酰亚胺 4 基) 马来酰亚胺(Ⅱ),反应收率达69%～85%。各步产物经1HNMR、IR确定结构。在研究脱水环合反应的过程中,分离得到其中一种产物的反应中间体:N (N 丁基 邻苯二甲酰亚胺 4 基) 氨基马来酰酸乙酸酐(Ⅲ),由此推测该反应为五元环过渡态的SN2亲核取代机理。

Six N-(N-substituted-phthalimide-4-yl) maleimides(Ⅱ) were prepared using the corresponding N-substituted-4-aminophthalimides and maleic anhydride as starting material.Under N_2 atmosphere,maleic anhydride and N-substituted-4-aminophthalimides were stirred in acetone at room temperature for 2.5 h to give N-(N-substituted-phthalimide-4-yl) maleamic acids(Ⅰ)in >90% yield.Cyclodehydration of maleamic acids(Ⅰ)to the corresponding maleimides(Ⅱ)using acetic anhydride as dehydration agent in acetone was performanced at reflux temperature for 0.5 h in 69%～85% yield.All compounds were identified by IR and ~1HNMR.During the cyclodehydration reaction,an intermediate N-(N-butyl-phthalimide-4-yl) maleamic acetic anhydride was separated.Therefore, the mechanism of cyclodehydration of maleamic acid to maleimide was considered to be SN2 nucleophilic substitution forming the intermediate with five-membered ring.