發(fā)布時(shí)間：2018-01-06 16:27

  本文關(guān)鍵詞：有機(jī)不對(duì)稱催化合成二氫香豆素和α,α-雙取代非天然α-氨基酸酯　出處：《湖北工業(yè)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 二氫香豆素 萘酚 三氟亞乙基吲哚酮 α-氨基酸 吲哚 氮雜傅克烷基化

【摘要】：第一部分二氫香豆素作為許多天然產(chǎn)物的核心骨架由于其多樣的結(jié)構(gòu)性和生物活性吸引了越來越多的關(guān)注。不同種類的二氫香豆素衍生物顯示出多樣的生物活性,部分已當(dāng)作藥物候選物,因此這類化合物的合成具有非常重要的意義。二氫香豆素的許多合成方法都已報(bào)道,但是用高效溫和的有機(jī)不對(duì)稱催化合成方式尤為矚目。在給體/受體觀念的指導(dǎo)下,鄰位上連有吸電子基團(tuán)的苯酚發(fā)生[4+2]環(huán)加成反應(yīng)是合成二氫香豆素骨架最常用的策略。盡管已經(jīng)有一些比較好的合成例子,但是開發(fā)出一種新的合成策略去構(gòu)建包含多功能轉(zhuǎn)變基團(tuán)的光學(xué)純二氫香豆素始終是一個(gè)比較有挑戰(zhàn)性的課題。在此,我們報(bào)道了在這一領(lǐng)域的最新研究成果,通過有機(jī)催化萘酚和3-三氟亞乙基吲哚酮的傅克烷基化/內(nèi)酯化反應(yīng)(新穎的[3+3]合成策略)合成二氫香豆素。我們發(fā)現(xiàn)該反應(yīng)僅需要2.5 mol%的奎寧衍生的四方胺催化劑就能以較好的效果(up to 99%yield and up to 98%ee,20:1 d.r.)得到α-芳基-β-CF3-二氫香豆素類化合物。在溫和條件下酚羥基進(jìn)攻吲哚酮的酰胺鍵發(fā)生內(nèi)酯化反應(yīng),這種分子內(nèi)酰胺鍵斷裂后發(fā)生內(nèi)酯化的反應(yīng)代表了合成二氫香豆素的新方法。更為重要的是將具有藥學(xué)活性的CF3引入到具有重要生物活性的二氫香豆素中,它可以增加母體化合物的代謝穩(wěn)定性和生物利用率。為了進(jìn)一步研究該不對(duì)稱傅克烷基化/內(nèi)酯化反應(yīng),我們對(duì)加成產(chǎn)物做了一些具有代表性的衍生,這些化合物均具有潛在的生物活性。第二部分高度對(duì)映選擇性的α,α-雙取代的α-氨基酸衍生物廣泛存在于天然產(chǎn)物、藥物分子和多功能材料中,在有機(jī)合成化學(xué)中,它也具有廣泛的應(yīng)用前景。有機(jī)催化親核試劑對(duì)映選擇性加成到α-酮酯提供了一種高效制備光學(xué)純?chǔ)?手性季碳中心氨基酸衍生物的方法。而吲哚和α-酮酯的不對(duì)稱氮雜傅克烷基化可以得到一系列連有吲哚和含有手性季碳中心的α-氨基酸類化合物。這類化合物可以用來合成很多天然產(chǎn)物和藥物分子。因此,我們報(bào)道了手性磷酸作用下吲哚和芳基環(huán)α-酮酯發(fā)生對(duì)映選擇性氮雜傅克烷基化反應(yīng),以較好的反應(yīng)條件(up to 85%yield and up to93%ee)得到α,α-雙取代非天然α-氨基酸酯衍生物。最后,我們對(duì)加成產(chǎn)物做了一些具有代表性的衍生轉(zhuǎn)變,它可以用來合成α-氨基酸酯。
[Abstract]:Part one: dihydrocoumarin, as the core skeleton of many natural products, has attracted more and more attention because of its diverse structure and biological activity. Different kinds of dihydrocoumarin derivatives show various biological activities. . Some have been used as drug candidates, so the synthesis of these compounds is of great significance. Many synthesis methods of dihydrocoumarin have been reported. Under the guidance of donor / acceptor concept, phenol with electron-absorbing groups on the ortho site is produced. [42] Cycloaddition reaction is the most commonly used strategy for the synthesis of dihydrocoumarin skeleton, although there are some good examples of synthesis. However, the development of a new synthesis strategy to construct optical pure dihydrocoumarin containing multifunctional transition groups has always been a challenging issue. In this paper, we report the latest research results in this field. Fourier alkylation / internal esterification of naphthol with 3-trifluoroethylindolone catalyzed by organic catalyst (novel. [Synthesis of dihydrocoumarin. We found that only 2.5 mol% Quinine derivative catalyst was needed for the synthesis of dihydrocoumarin. Up to 99 yield and up to 98. 偽 -aryl- 尾 -CF3-dihydrocoumarin compounds were obtained from 20: 1 d.r.) the amide-bonds of phenolic hydroxyl groups attacking indole ketones were esterified internally under mild conditions. The lactone reaction after the break of the molecular lactam bond represents a new method for the synthesis of dihydrocoumarin. More importantly, CF3 with pharmacological activity is introduced into dihydrocoumarin with important biological activity. It can increase the metabolic stability and bioavailability of the parent compounds. In order to further study the asymmetric Fourier alkylation / internal esterification reaction, we have made some representative derivatives of the addition products. These compounds have potential biological activities. The second part of the highly enantioselective 偽, 偽 -disubstituted 偽 -amino acid derivatives are widely found in natural products, drug molecules and multifunctional materials. In organic synthesis chemistry. It also has a wide application prospect. The enantioselective addition of organic catalytic nucleophilic reagent to 偽 -ketone ester provides an efficient method for the preparation of optically pure 偽 -chiral quaternary carbon-centered amino acid derivatives, while indoles and 偽 -keto esters. A series of 偽 -amino acid compounds with indole and chiral quaternary carbon centers can be obtained by asymmetric aza-Fourier alkylation. These compounds can be used to synthesize many natural products and drug molecules. The enantioselective aza-Fourier alkylation of indoles and aryl cyclic 偽 -ketones with chiral phosphoric acid was reported. 偽, 偽 -disubstituted unnatural 偽 -amino acid ester derivatives were obtained by yield up up to93 under better reaction conditions. Finally, 偽, 偽 -disubstituted natural 偽 -amino acid ester derivatives were obtained. We have made some representative derivatives of addition products, which can be used to synthesize 偽-amino acid esters.
【學(xué)位授予單位】：湖北工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O621.251;O629

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本文編號(hào)：1388653