【摘要】：手性在自然界中是普遍常見(jiàn)的現(xiàn)象,在生命過(guò)程中發(fā)揮著重要且獨(dú)特的作用。手性藥物因其不同的生物學(xué)效應(yīng),引起廣泛重視。發(fā)展好的對(duì)映選擇性、高催化活性的催化劑具有重要的意義。本文從L-色氨酸出發(fā)合成了一系列軸手性雙咔啉氮氧催化劑。以1位不同取代基咔啉醛為底物,初步探討了其不對(duì)稱(chēng)催化活性。并對(duì)此系列化合物生物活性進(jìn)行初步研究。第一章,醛的不對(duì)稱(chēng)烯丙基化反應(yīng)的研究進(jìn)展概述。第二章,在課題組既往研究工作基礎(chǔ)上,繼續(xù)探討軸手性雙咔啉氮氧化合物對(duì)大結(jié)構(gòu)骨架醛的不對(duì)稱(chēng)催化活性。以常見(jiàn)的L-色氨酸為原料,經(jīng)多步反應(yīng)合成了多個(gè)1,1’-雙咔啉氮氧軸手性催化劑。同時(shí)以L-色氨酸為原料,經(jīng)多步反應(yīng)合成系列1-取代-3-甲酰基-9-甲基咔啉醛。以此大結(jié)構(gòu)骨架醛為底物研究軸手性雙咔啉氮氧化合物的不對(duì)稱(chēng)催化活性。實(shí)驗(yàn)結(jié)果表明:反應(yīng)能夠在-25℃下16 h內(nèi)順利完成。該類(lèi)催化劑在三氯烯丙基硅烷對(duì)大結(jié)構(gòu)醛的不對(duì)稱(chēng)烯丙基化反應(yīng)中表現(xiàn)出了優(yōu)異的對(duì)映選擇性:當(dāng)3,3’位有環(huán)戊基取代時(shí)對(duì)大底物醛反應(yīng)ee值最優(yōu),最高ee值96%。共合成新結(jié)構(gòu)咔啉類(lèi)化合物80個(gè)。第三章通過(guò)VCD、ECD、IR、OR檢測(cè),計(jì)算值與實(shí)驗(yàn)值分析比較確定軸手性雙咔啉氮氧催化劑及不對(duì)稱(chēng)催化反應(yīng)手性產(chǎn)物的絕對(duì)構(gòu)型。第四章對(duì)系列1-取代-3甲酰基-9甲基咔啉醛合成的中間產(chǎn)物及經(jīng)烯丙基化不對(duì)稱(chēng)催化反應(yīng)后手性產(chǎn)物進(jìn)行生物活性研究。體外抗腫瘤活性篩選結(jié)果表明:部分衍生物抑制腫瘤細(xì)胞株生長(zhǎng),具有一定的細(xì)胞毒性。手性催化產(chǎn)物的R型、S型及外消旋體的抑制作用存在統(tǒng)計(jì)學(xué)意義上的顯著差別(p㩳0.05)。初步構(gòu)效關(guān)系的研究表明:9位H取代效果好于-CH_3取代;3位取代效果:酯基好于-CH_2OH取代,好于手性烯丙醇。
[Abstract]:Chirality is a common phenomenon in nature and plays an important and unique role in the life process. Chiral drugs have attracted wide attention because of their different biological effects. It is of great significance to develop enantioselectivity and catalyst with high catalytic activity. In this paper, a series of chiral dicarboline nitroxide catalysts were synthesized from L-tryptophan. The asymmetric catalytic activity of different substituted carbolaldehyde was studied. The biological activity of this series of compounds was preliminarily studied. In chapter 1, the progress of asymmetric allylation of aldehydes is summarized. In the second chapter, based on the previous work of our research group, we continue to study the asymmetric catalytic activity of chiral dicarboline nitroxides for large structure skeleton aldehydes. In this paper, a number of chiral catalysts were synthesized from common L-tryptophan by multi-step reaction. A series of 1-substituted-3-formyl-9-methyl carbolaldehyde was synthesized from L-tryptophan by multi-step reaction. The asymmetric catalytic activity of chiral dicarboline nitroxides was studied by using the macrostructure skeleton aldehydes as the substrate. The experimental results show that the reaction can be successfully completed within 16 hours at -25 鈩，

本文編號(hào)：2259312