位点可控的二乙氧磷酰化壳寡糖的合成

以壳寡糖(COS)为原料, 二乙基亚磷酸酯(DEPH)为磷酰化试剂, 通过改变反应体系中三乙胺(TEA)的用量控制二乙基磷酰基的进攻位点, 实现了2-N和3,6-O位点二乙基亚磷酰化壳寡糖衍生物的合成, 制备了N-二乙氧磷酰化壳寡糖及N,O,O-二乙氧磷酰化壳寡糖, 并采用单一变量法对合成条件进行了优化, 用31P NMR对产物进行了跟踪分析. 合成N-二乙氧磷酰化壳寡糖的最优反应条件为2 g COS, nCOS∶nTEA=1∶6, nCOS∶nDEPH=1∶3, 滴加DEPH和CCl4的时间为2 h, 低温反应2 h, 在该优化条件下产物的磷含量为1.50%(质量分数). 合成N,O,O-二乙氧磷酰化壳寡糖的最优反应条件为2 g COS, nCOS∶nTEA=1∶6, nCOS∶nDEPH=1∶5, 滴加DEPH和CCl4 的时间2 h, 低温反应4 h, 常温反应8 h, 在该优化条件下产物的磷含量为3.42%. 对合成反应的可能机理进行了推测.

Site-Controlled Synthesis and the Optimum Reaction Conditions of Diethoxy Phosphoryl Chitooligosaccharides

Using low molecular weight chitooligosaccharide and dialkyl phosphite as raw materials, the site-controlled diethoxy phosphoryl chitooligosaccharides were synthesized through varying the amount of triethlamine. Then, N-diethoxy phosphoryl chitooligosaccharide and N,O,O-diethoxy phosphoryl chitooligosaccharide were obtained. The optimal synthetic conditions were studied by the single factor variable method. And the optimum reaction conditions of N-diethoxy phosphoryl chitooligosaccharide were as follows: 2 g COS, nCOS∶nTEA=1∶6, nCOS∶nDEPH=1∶3, 2 h for the time of dropwise for the solution of DEPH in CCl4, 2 h for the time at the low temperature. The maximum phosphorus content achieves 1.50% under the optimum conditions. The optimum reaction conditions of N,O,O-diethoxy phosphoryl chitooligosaccharide were as follows: 2 g COS, nCOS∶nTEA=1∶6, nCOS∶nDEPH=1∶5, 2 h for the time of dropwise for the solution of DEPH in CCl4, 4 h for the time at the low temperature, 8 h for the reaction time at the room temperature. The maximum phosphorus content achieves 3.42% under the optimum conditions. Moreover, a possible reaction mechanism was proposed to explain the formation of diethoxy phosphoryl chitooligosaccharides.