新鱼腥草素钠缩合反应机制探讨及聚合物结构鉴定

The condensation mechanism of sodium new houttuyfonate and determination of the chemical structure of condensation products

为探讨新鱼腥草素钠缩合反应机制并鉴定稳定化缩合产物的化学结构,制备了二聚物并进行转化反应,采用LC-DAD-MS/MS联用技术分析转化产物的紫外吸收特征及质谱信息,采用紫外分光光度法考察转化动力学及转化半衰期。经有机溶剂萃取及柱层析分离纯化,制备了稳定化缩合产物对照品,采用红外、高分辨质谱和核磁共振技术进行结构鉴定,并将LC-MS/MS分析结果与二聚物转化产物进行比较。二聚物结构不稳定,在水溶液中易解离生成游离的十二酰乙醛,进而发生三分子环合加成?原位脱水缩合反应,生成含六元环稳定结构的1,3,5-三-(十二烷酰基)-苯(三聚物),转化反应符合二级动力学方程,25℃(298K)和100℃(373k)条件下转化半衰期分别为3.17h和6.39min。二聚物系缩合过程中的中间过渡状态,推测新鱼腥草素钠注射液中的缩合产物主要以三聚物的形式存在。

To study the condensation mechanism of sodium new houttuyfonate, and determinate the chemical structure of condensation products, dimer was prepared, and LC-DAD-MS/MS multiple techniques were employed to investigate the ultraviolet absorption feature and mass spectrum of transformation solution of dimer, and the transformation kinetics and half-life were studied by ultraviolet spectrophotometry. The pure substance of stable condensation product was obtained by extracting with organic solvent and purifying with column chromatography, the chemical structure of this substance was identified by assaying of IR, HR-ESI-MS and NMR, and the data of LC-MS/MS were compared with that of transformation products of dimer. The results indicated that the dimer is unstable, it will be rapidly dissociated in aqueous solution to form free new houttuyfonate and then cycloaddition reaction will occur and followed by an in situ dehydration to generate 1, 3, 5-tri（dodecanoyl） benzene （trimer） with a six-ring which is stable in aqueous solution. The transformation process may fit second-order kinetics, and the half-times were found to be 3.17 hours at 25 ℃ （298 K） and 6.39 min at 100 ℃ （373 K）, separately. It suggests that dimer is an intermediate in condensation reaction, and the end condensation product of sodium new houttuyfonate injection may exist as trimer.