【作者】 刘莉；

【导师】 朱华结；

【作者基本信息】 河北大学 ， 动物学， 2016， 博士

【摘要】 手性在自然界中是普遍常见的现象,在生命过程中发挥着重要且独特的作用。手性药物因其不同的生物学效应,引起广泛重视。发展好的对映选择性、高催化活性的催化剂具有重要的意义。本文从L-色氨酸出发合成了一系列轴手性双咔啉氮氧催化剂。以1位不同取代基咔啉醛为底物,初步探讨了其不对称催化活性。并对此系列化合物生物活性进行初步研究。第一章,醛的不对称烯丙基化反应的研究进展概述。第二章,在课题组既往研究工作基础上,继续探讨轴手性双咔啉氮氧化合物对大结构骨架醛的不对称催化活性。以常见的L-色氨酸为原料,经多步反应合成了多个1,1’-双咔啉氮氧轴手性催化剂。同时以L-色氨酸为原料,经多步反应合成系列1-取代-3-甲酰基-9-甲基咔啉醛。以此大结构骨架醛为底物研究轴手性双咔啉氮氧化合物的不对称催化活性。实验结果表明:反应能够在-25℃下16 h内顺利完成。该类催化剂在三氯烯丙基硅烷对大结构醛的不对称烯丙基化反应中表现出了优异的对映选择性:当3,3’位有环戊基取代时对大底物醛反应ee值最优,最高ee值96%。共合成新结构咔啉类化合物80个。第三章通过VCD、ECD、IR、OR检测,计算值与实验值分析比较确定轴手性双咔啉氮氧催化剂及不对称催化反应手性产物的绝对构型。第四章对系列1-取代-3甲酰基-9甲基咔啉醛合成的中间产物及经烯丙基化不对称催化反应后手性产物进行生物活性研究。体外抗肿瘤活性筛选结果表明:部分衍生物抑制肿瘤细胞株生长,具有一定的细胞毒性。手性催化产物的R型、S型及外消旋体的抑制作用存在统计学意义上的显著差别（p﹤0.05）。初步构效关系的研究表明:9位H取代效果好于-CH₃取代;3位取代效果:酯基好于-CH₂OH取代,好于手性烯丙醇。更多还原

【Abstract】 Chiral molecules widely distribute in nature and play an important and unique role in life. Chiral drugs cause wide attentions because of their different biological effects. It has a great significance to develope chiral catalysts with high enantioselectivity and high activity. In this study,L- tryptophan was used as a major starting material for synthesis of axial chiral biscarboline N-O catalysts. We studied their applications in enantioselective allylation of trichlorohydrosililane to bulky substituted aldehydes. Initially,the compounds involved in the study were well used in the cytotoxicity of examinations.Chapter one is the research review of asymmetric allylation of aldehydes mediated by Lewis acids and catalyzed by Lewis bases.In chapter two,we explored the axial chiral biscarboline-N, N′-dioxide catalysts with ester moiety on C-3,C-3′. Several axial chiral catalysts were obtained as enantiomerically purity. Twelve bulky substituted carboline aldehydes were synthesized from L-tryptophan.We studied enantioselective of all the axial chiral bicarboline-N, N′-dioxid catalysts in the addition of trichlorohydrosililane to the aldehydes.The results showed that the reaction could be successfully accomplished in 16 h at 25℃, leading to the corresponding chiral alcohol in high yields and ee% values. The best catalyst can achieve an enantioselectivity as high as 96%. we’ve got 80 new compounds.In chapter three,we studied the stereochemistry of the catalyst and the chiral alcohol by comparison of calculated and experimental VCD,ECD andOR,respectively.In chapter four, new carboline derivatives obtained from L-tryptophan were used for screen of cytotoxic activity against five human cancer cell lines in vitro by MTT assay. Some of them exhibited potential uses in future time. Productions of chiral catalysis have significant difference of cytotoxic activity(p<0.05).We studied the structure-function relationship.更多还原