紫杉醇的核磁共振谱及其分子几何构型的从头算研究  

Ab Inito Study on δ 1~H NMR and δ 13~C NMR of Taxol and It′s Molecular Geometry

作　　者：许旋[1] 徐志广[1] 罗一帆[2] 

机构地区：[1]华南师范大学化学系,广州510631 [2]中山医科大学天然药物研究室,广州510089

出　　处：《物理化学学报》2002年第5期420-425,共6页Acta Physico-Chimica Sinica

基　　金：广东省科技攻关基金(2KB01202S)资助项目

摘　　要：应用规范不变原子轨道GIAO法在HF/6-31G水平计算了MM3、PM3和HF/STO-3G三种最优分子构型下紫杉醇的δ1H-NMR和δ13C-NMR.对NMR化学位移计算值与实验值的对比和误差的统计和分析表明,采用HF/STO-3G优化的几何构型计算得到的化学位移误差最小,因此这一构型与实际分子最为接近.从理论构型得到4-OAc与3'-H的距离为0.2663nm,4-OAc与3'-Ph的距离为0.3104nm,4-OAc与2-OCOPh的距离为0.3707nm,支持了Williams等关于紫杉醇分子内存在NOE(nuclearoverhausereffect)效应及Velde等关于在极性溶剂中4-OAc与3'-Ph、2-OCOPh形成分子内疏水簇的观点.The geometrical conformation of taxol has been optimized by MM3,PM3 and HF/STO 3G method,respectively.An ab initio GIAO method at HF/6 31G level has been used to predict theoretically 1H NMR and 13C NMR chemical shifts for the conformations by three geometry optimization methods.The results show that the calculated δ 1H NMR and δ 13C NMR for the geometrical conformation optimized by HF/STO 3G are the most accurate in comparison with experimentally observed data.It is inferred that,therefore,the geometrical conformation optimized by HF/STO 3G must probably be approximate to the real one of taxol in d6 DMSO D2O 70%.From the geometrical conformation of taxol optimized by HF/STO 3G,the distances between 4 OAc and 3′ H,4 OAc and 3′ Ph,4 OAc and 2 OCOPh are found to be 0.266 3 nm,0.310 4 nm and 0.370 7 nm,respectively.These distances are within the effective acting distances producing nuclear overhauser effect (NOE),which theoretically supports Williams′ view that there is a NOE effect in taxol molecule,and Velde′s view that there is a hydrophobic cluster formed by 4 OAc,3′ Ph and 2 OCOPh in taxol molecule.

关 键 词：紫杉醇 核磁共振谱 规范不变原子轨道法 从头算 化学位移 几何构型优化 抗癌药 药物化学 

分 类 号：O657.2[理学—分析化学]