紫杉醇C13侧链的硒代合成及其结构性质

Synthesis and microstructure properties of Se- C_(13) side chain analogue

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.

The analogs of taxol C13 are synthesized by selenium modification of its side chain.With chiral men-thol as raw material, C13 side chain containing selenium acylamide are synthesize through Darzen condensation, azide substitution, reduction, amidolysis, reduction and hydrolysis.The structure of target compound is charac-terized by IR, elemental analysis, atomic fluorescence.The density functional theory（B3LYP）method is adopted to conduct gas and solution simulation for the study of the microstructure and properties of target compound.The results show a good agreement between experimental and the calculated IR spectra, and theoretical predictions show that the objects is a typical amphoteric reagent, the replacement of Se can increase active sites and enhance solubility.The results of this study can provide theoretical and experimental basis for a variety of related studies, such as the quantitative studies of the structure-activity relationship of such compounds, the establishment of pharmacophore model of the compounds and the structure modification of the lead compound chemicals.