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用Se元素修饰紫杉醇C13侧链合成硒代C13类拟物.以手性薄荷醇为原料,通过Darzen缩合、叠氮化、还原、胺解、水解等,合成含硒酰胺的C13侧链,目标物用IR、元素分析、原子荧光等手段进行结构表征.同时采用密度泛函B3LYP方法,6-31+G*水平基组对目标物的微观结构及其性质进行气态、溶液模拟计算.分析比较实验、计算的IR光谱吻合较好.并对目标物微观性质进行理论预测,为典型的两性试剂,Se的取代可增加活性部位,增强溶解性.本研究成果为该类化合物的定量构效关系研究和药效团模型的建立以及先导化合物的化学结构修饰改造提供理论依据及实验基础.
Se element is used to modify the side chain of paclitaxel C13 to synthesize selenocysteine C13 analogues. The selenide C13 side chain is synthesized by chiral menthol as Darzen condensation, azide, reduction, amineysis and hydrolysis. The structures were characterized by means of IR, elemental analysis and atomic fluorescence spectroscopy, and the microstructure and properties of target were calculated by density functional B3LYP method and 6-31 + G * horizontal basis set. The experimental results show that the calculated IR spectra agree well with each other and the theoretical prediction of the microscopic properties of the target is typical amphoteric reagent.The substitution of Se can increase the active site and enhance the solubility.The results of this study are the quantitative structure-activity relationship Research and pharmacophore model establishment as well as the lead compound chemical structure modification provide theoretical basis and experimental basis.