本文選題：C-H　切入點：鍵活化　出處：《江南大學(xué)》2014年碩士論文

【摘要】：碳碳鍵以及碳雜鍵的形成是藥物合成領(lǐng)域重要的研究內(nèi)容之一。高效、高選擇性地形成C-C、C-X鍵的新反應(yīng)、新途徑將會顯著地提高目標(biāo)產(chǎn)物的合成效率，繼而對現(xiàn)代藥物分子合成與發(fā)展產(chǎn)生積極的影響，具有重大的理論意義和應(yīng)用價值。目前，通過過渡金屬催化的C-H鍵活化直接來來構(gòu)筑C-C、C-X鍵的方法，因其具有步驟短、排放的廢物少、原子經(jīng)濟(jì)性好等優(yōu)勢已成為有機(jī)合成中的研究熱點。 本論文中重點研究了金和鐵催化的sp3C-H鍵的活化反應(yīng)，合成了一些可能具有生物活性的活性單元，為藥物分子的合成尋找到一條簡潔、高效的路徑，并對后期的金屬催化的不對稱合成提供理論基礎(chǔ)。具體研究內(nèi)容包括：1.金催化的N-芳基四氫異喹啉的吲哚化 吲哚是非常重要的含氮化合物，作為多功能的分子構(gòu)建結(jié)構(gòu)單元，在合成一些具有重要生物活性的化合物中起著非常重要的作用。近年來，人們致力于發(fā)展一條新型、環(huán)境友好、高效、高選擇性的吲哚衍生物的合成方法。本文中，我們以NaAuCl4作為催化劑，過氧叔丁醇(TBHP)為氧化劑，在常溫反應(yīng)條件下，成功實現(xiàn)了N-苯基四氫異喹啉氮鄰位的sp3C-H鍵與吲哚sp2C-H鍵交叉脫氫偶聯(lián)，合成了一系列可能具有重要生物活性的吲哚衍生物。該方法具有高產(chǎn)率、高區(qū)域選擇性、適用范圍廣泛、操作簡單、條件溫和等優(yōu)勢。2.鐵催化的sp3C-H鍵的氧化磷酸化 含磷的化合物，特別是-氨基磷酸衍生物是眾多生物活性分子的前體，其中-氨基磷酸酯化合物及其相應(yīng)的-氨基磷酸化合物因其與眾多氨基酸結(jié)構(gòu)相類似，在有機(jī)化學(xué)和藥物化學(xué)上有著巨大的價值。本文中，，我們以FeCl3為催化劑，空氣作為氧化劑，在溫和的條件下實現(xiàn)了叔胺氮的鄰位碳原子上sp3C-H與亞磷酸二烷基酯、部分二芳基磷氧化合物的H-P鍵的交叉脫氫偶聯(lián)。安全、方便、環(huán)境友好、高效地合成了一系列可能具有重要生物活性的-氨基磷酸酯衍生物。
[Abstract]:The formation of carbon-carbon bond and carbon heterodyne bond is one of the important research contents in the field of drug synthesis. The new reaction of high efficiency and high selectivity to form C-C-X bond will significantly improve the synthesis efficiency of the target product. It has great theoretical significance and application value. At present, the method of constructing C-CU C-X bond directly through transition metal-catalyzed C-H bond activation, because of its short step, is very important for the synthesis and development of modern drug molecules. The advantages of low waste emission and good atomic economy have become a hot spot in organic synthesis. In this paper, the activation of sp3C-H bond catalyzed by gold and iron was studied, and some active units with biological activity were synthesized, and a simple and efficient route was found for the synthesis of drug molecules. It also provides a theoretical basis for the asymmetric synthesis of metal-catalyzed anaphase. The specific research contents include: 1. Indolation of N-aryl tetrahydroisoquinoline catalyzed by gold. Indole is a very important nitrogen-containing compound. As a multifunctional molecular structure unit, indole plays a very important role in the synthesis of some compounds with important biological activities. In this paper, we use NaAuCl4 as catalyst and TBHPas as oxidant, under the condition of normal temperature reaction, the synthesis of indole derivatives is environmentally friendly, efficient and highly selective. A series of indole derivatives with important biological activity were successfully synthesized by cross-dehydrogenation of N-phenyl-tetrahydroisoquinoline nitrogen-ortho sp3C-H bond and indole sp2C-H bond. The method has high yield, high region selectivity and wide range of application. Simple operation, mild conditions and other advantages .2.Oxidation phosphorylation of iron catalyzed sp3C-H bond. Phosphorus-containing compounds, in particular, derivatives of -aminophosphoric acid, are precursors of many bioactive molecules, among which aminophosphate compounds and their corresponding amino acid phosphate compounds are similar in structure to many amino acids, In this paper, using FeCl3 as catalyst and air as oxidant, we have achieved sp3C-H and dialkyl phosphite on O-carbon atom of tertiary amine nitrogen under mild conditions. A series of potentially important biologically active-aminophosphate derivatives were synthesized by cross-dehydrogenation coupling of some diarylphosphoric compounds with H-P bonds which are safe, convenient, environmentally friendly and efficient.
【學(xué)位授予單位】：江南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R914.5

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