【作者】 刘勇；

【导师】 江涛；

【作者基本信息】 中国海洋大学 ， 生药学， 2003， 硕士

【摘要】 本文在计算机辅助设计的指导下，对一类顺丁烯二酸酐衍生物与氨基糖相连的化合物进行了结构改造。 结构改造包括：改变糖环部分保护基，合成了乙酰基保护的、苯甲酰基保护的和苄基保护的2-脱氧-N-葡萄糖酰胺丙烯酸(化合物A、B、C)；改变氢键供体和共轭体系，合成了乙酰基保护的2-脱氧-N-葡萄糖丁烯二酰亚胺、乙酰基保护的2-脱氧-N-葡萄糖酰胺丙酸和2-脱氧-N-葡萄糖酰胺邻苯甲酸；去掉糖环上的保护基，增大糖环极性，合成了2-脱氧-N-葡萄糖酰胺邻苯甲酸；改变糖环与共轭体系的空间位置、改变糖的种类分别合成了1-脱氧-N-葡萄糖酰胺丙烯酸、1-脱氧-N-半乳糖酰胺丙烯酸。其中，化合物A、化合物B、化合物C得到了晶型较好的单晶，有待于晶体结构分析。对上述化合物用红外光谱和核磁共振技术进行了结构确证。用异头效应和邻基参与效应解释了两种中间体：1-溴乙酰糖和1-叠氮乙酰糖的构型。 另外，本文还以抑瘤活性较好的化合物A和化合物B为配体，与三氯化钐、三氯化镨、三氯化钕、三氯化镝合成了三类，共九种稀土金属配合物。通过对稀土元素含量、氯元素含量的滴定，以及红外光谱，核磁共振技术对配合物的结构进行了初步的确证，推测了配合物可能的结构分别是：配合物A系列Ln以三个共价离子键与羧基氧相连，三个NH的N以及二个EtOH的O与Ln形成配位键，形成Ln系元素以八配位结构存在。配合物A系列Ln以三个共价离子键与羧基氧相连，三个NH的N与Ln形成配位键，苯甲酰基保护的糖分散在金属配合物的外围，形成Ln系元素以六配位结构存在。配合物C中Ln以三个共价离子键与羧基氧相连，三个NH的N与Ln形成配位键，形成Ln系元素以六配位结构存在。对含不同保护基的糖配体与稀土金属形成的配合物的性质差异进行了探讨。为进一步研究，利用稀土离子的生物探针作用来研究药物在体内的作用机理，做了必要的准备。 本文所合成的部分化合物以及配合物的活性测试尚在进行当中。配合物单晶结构测定正在进行中。更多还原

【Abstract】 Based on the results of computer added drug design, a series of glucosamines with maleic anhydride derivative have been structural modifided and synthesized.This structural modification are comprised by (1) changing the protected groups of saccharide part to sythesize the compounds 2-amino- glucose linking with 3-formyl-propenoic acid with the deferent hydroxyl protected groups, such as acetyl, benzoyl, benzyl on saccharide; (Compound A, B andC) (2)change hydrogen bond donor and conjugate system in order to sythesizing the compounds 2-deoxyglucose linking with maleic acyl imide with the hydroxyl protected groups, acetyl, on saccharide and 2-amino-glucose linding with 3-formyl-propanic acid with the hydroxyl protected groups, acetyl, on saccharide, 2-amino-glucose linding with 2-formylbenzoic acid; (3)Deprotect those protected groups of saccharide in order to increasing their polarity, sythesize the compound 2-amino-glucose linking with 2-formylbenzoic acid; (4)change the spatial arrangement and the kind of sacchride, sythesize the compounds 1-ammo-glucose, 1-amino-galactose linking with 3-formyl-propenic acid with the hydroxyl protected groups, acetyl, on saccharide. Among of these compounds, A, B and C have been fostered their singal crystals which now is being testing their crystal structure. All compounds have been characterized by IR and NMR spectrum. The configuration of 1-bromido-peracetyl-glucose and 1-azido-peracetyl-glucose have been explained by anomeric effect and ortho-groups attached effect.Moreover, three series of Lantnide-sccharide complexes hve been firstly synthesized by the reaction of Lanthanide tricloride with the compounds d A , B as the ligand at the different ratio. The structure have been characterized by the NMR, IR and elemental aanalysis of metal and chloride. The distinction of the complexescharacters which have been synthesized by the saccharide including different protected groups and Lanthanide, have been discussed. The necessary preparation have been done to learn the mechanism of medicine in vivo by bio-probe effect of rare earth.Further determination of bioactivities of all comounds are currently researching. The singal crystals now is being fostering and testing their crystal structure.更多还原