本文選題：四氫-β-咔啉類　切入點：Pictet-Spengler反應　出處：《天津科技大學》2014年碩士論文

【摘要】：四氫-β-咔啉類化合物是屬于分布于自然界的吲哚生物堿,具有抗腫瘤、抗菌、抗高血壓及治療阿爾茲海默癥等多種生物活性,近年來,四氫-p-咔啉類化合物以其獨特的性質和結構,引起越來越多的人關注。雙吲哚類衍生物作為雜環(huán)化合物一種重要的類別所為人知曉,并且是研發(fā)和制藥工業(yè)中具有生物活性的中間產品,不僅可以增加人體內荷爾蒙的自然代謝,而且在預防癌癥方面也是有效的。Pictet-Spengler縮合反應是在1911年被AmePictet和TheodorSpengler發(fā)現的,現已經成為了在合成p-咔啉類化合物方面中至關重要的方法,除此之外,它也應用于更多的復雜結構吲哚生物堿的合成。 論文運用Pictet-Spengler反應方法,合成四氫-p-咔啉類化合物。首先以吲哚和5-溴吲哚為原料,經過親核加成、環(huán)合、還原、Pictet-Spengler反應等5-6步反應,合成了8個四氫-p-咔啉類衍生物,通過對不同反應試劑、反應時間和反應溫度的優(yōu)化,反應的總產率均達到20%-25%。利用核磁共振氫譜、碳譜等方法對目標化合物的結構進行表征。課題以吲哚為原料,經過付克�；�、黃鳴龍反應、還原、Pictet-Spengler反應等4-5步反應,合成了6個雙吲哚結構化合物,通過對不同反應試劑、反應時間和反應溫度的優(yōu)化,反應的總產率均達到27%～37%。利用核磁共振氫譜、碳譜,質譜及二維核磁譜圖等方法對目標化合物的結構進行表征。綜上所述,合成14個目標化合物和4個中間產物,其中11個化合物未見報道。 在此基礎上,對雙吲哚類化合物進行了體外腫瘤細胞抑制活性的測試,所選用的三種癌細胞為人白血病細胞(K562)、人肝癌細胞(HepG2)和人結腸癌細胞(HT-29)�；钚詼y試結果為：2,2'-二(3,3'-N-芐基-3-1H-吲哚基丙酰胺)苯基甲烷(化合物13),2,2'-二(3,3'-N-芐基-3-1H-吲哚基丙酰胺)對硝基苯基甲烷(化合物16),2,2'-二(3,3'-N-芐基-3-1H-吲哚基丙酰胺)對氟苯基甲烷(化合物17),2,2'-二(3,3'-N-芐基-3-1H-吲哚基丙酰胺)間甲氧基苯基甲烷(化合物18)對人白血病細胞(K562)腫瘤細胞有著一定的生長抑制作用,其IC50值分別為56.19μM,90.71μM,58.55μM,67.22μM,對人肝癌細胞(HepG2)和人結腸癌細胞(HT-29)均無抑制作用。測試結果表明：與吲哚類似物反應的苯甲醛,苯環(huán)對位連有弱吸電基與間位連有供電基的分子,其抗腫瘤活性較好。
[Abstract]:Tetrahydro- 尾 -carboline is an indole alkaloid distributed in nature. It has many biological activities such as anti-tumor, antibacterial, anti-hypertension and treating Alzheimer's disease.Tetrahydrogen-p-carboline compounds have attracted more and more attention due to their unique properties and structures.Bisindole derivatives are known as an important class of heterocyclic compounds and are bioactive intermediates in the R & D and pharmaceutical industries, which not only increase the natural metabolism of hormones in humans,And also effective in preventing cancer. Pictet-Spengler condensation was discovered by AmePictet and TheodorSpengler in 1911 and has become a crucial method in the synthesis of p-carboline compounds.It is also used in the synthesis of more complex indole alkaloids.In this paper, tetrahydrogen-p-carboline compounds were synthesized by Pictet-Spengler reaction.Firstly, eight tetrahydro-p-carboline derivatives were synthesized from indole and 5-bromoindole by 5-6 steps of nucleophilic addition, cyclization and reduction Pictet-Spengler reaction.The total yield of the reaction was 20-25.The structure of the target compounds was characterized by nuclear magnetic resonance spectroscopy and carbon spectroscopy.In this paper, six diindole compounds were synthesized from indole by 4-5 steps of Fu acylation, Huang Minglong reaction, reduction Pictet-Spengler reaction and so on. Different reaction reagents, reaction time and reaction temperature were optimized.The total yield of the reaction was 27% and 37% respectively.The structure of the target compound was characterized by nuclear magnetic resonance spectroscopy, carbon spectrum, mass spectrometry and two-dimensional NMR spectroscopy.In conclusion, 14 target compounds and 4 intermediates were synthesized, of which 11 compounds were not reported.On this basis, the inhibitory activity of diindole compounds on tumor cells was tested in vitro. Three kinds of cancer cells were selected as human leukemic cells, human hepatocellular carcinoma cell line (HepG2) and human colon cancer cell line (HT-29C).Their IC50 values were 56.19 渭 m ~ (90.71 渭 m) and 58.55 渭 M ~ (67.22 渭 M), respectively, which had no inhibitory effect on human hepatoma cell line HepG2) and human colon cancer cell line (HT-29).The results showed that the benzaldehyde, benzaldehyde ring with weak electricity-absorbing group and mesopotopic power supply group reacted with indole-analogue, and the anti-tumor activity of benzaldehyde was better than that of other molecules.
【學位授予單位】：天津科技大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914.5;R96

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