發(fā)布時(shí)間：2018-04-06 07:40

  本文選題：四氫-β-咔啉類　切入點(diǎn)：Pictet-Spengler反應(yīng)　出處：《天津科技大學(xué)》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(lái),四氫-p-咔啉類化合物以其獨(dú)特的性質(zhì)和結(jié)構(gòu),引起越來(lái)越多的人關(guān)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(chǎn)品,不僅可以增加人體內(nèi)荷爾蒙的自然代謝,而且在預(yù)防癌癥方面也是有效的。Pictet-Spengler縮合反應(yīng)是在1911年被AmePictet和TheodorSpengler發(fā)現(xiàn)的,現(xiàn)已經(jīng)成為了在合成p-咔啉類化合物方面中至關(guān)重要的方法,除此之外,它也應(yīng)用于更多的復(fù)雜結(jié)構(gòu)吲哚生物堿的合成。 論文運(yùn)用Pictet-Spengler反應(yīng)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(jīng)過親核加成、環(huán)合、還原、Pictet-Spengler反應(yīng)等5-6步反應(yīng),合成了8個(gè)四氫-p-咔啉類衍生物,通過對(duì)不同反應(yīng)試劑、反應(yīng)時(shí)間和反應(yīng)溫度的優(yōu)化,反應(yīng)的總產(chǎn)率均達(dá)到20%-25%。利用核磁共振氫譜、碳譜等方法對(duì)目標(biāo)化合物的結(jié)構(gòu)進(jìn)行表征。課題以吲哚為原料,經(jīng)過付克�；�、黃鳴龍反應(yīng)、還原、Pictet-Spengler反應(yīng)等4-5步反應(yīng),合成了6個(gè)雙吲哚結(jié)構(gòu)化合物,通過對(duì)不同反應(yīng)試劑、反應(yīng)時(shí)間和反應(yīng)溫度的優(yōu)化,反應(yīng)的總產(chǎn)率均達(dá)到27%～37%。利用核磁共振氫譜、碳譜,質(zhì)譜及二維核磁譜圖等方法對(duì)目標(biāo)化合物的結(jié)構(gòu)進(jìn)行表征。綜上所述,合成14個(gè)目標(biāo)化合物和4個(gè)中間產(chǎn)物,其中11個(gè)化合物未見報(bào)道。 在此基礎(chǔ)上,對(duì)雙吲哚類化合物進(jìn)行了體外腫瘤細(xì)胞抑制活性的測(cè)試,所選用的三種癌細(xì)胞為人白血病細(xì)胞(K562)、人肝癌細(xì)胞(HepG2)和人結(jié)腸癌細(xì)胞(HT-29)�；钚詼y(cè)試結(jié)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(duì)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(duì)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(duì)人白血病細(xì)胞(K562)腫瘤細(xì)胞有著一定的生長(zhǎng)抑制作用,其IC50值分別為56.19μM,90.71μM,58.55μM,67.22μM,對(duì)人肝癌細(xì)胞(HepG2)和人結(jié)腸癌細(xì)胞(HT-29)均無(wú)抑制作用。測(cè)試結(jié)果表明：與吲哚類似物反應(yīng)的苯甲醛,苯環(huán)對(duì)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(xué)位授予單位】：天津科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.5;R96

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