金属催化的碳氢活化在药物活性单元合成中的应用

发布时间：2018-03-28 03:02

本文选题：C-H　切入点：键活化　出处：《江南大学》2014年硕士论文

【摘要】：碳碳键以及碳杂键的形成是药物合成领域重要的研究内容之一。高效、高选择性地形成C-C、C-X键的新反应、新途径将会显著地提高目标产物的合成效率，继而对现代药物分子合成与发展产生积极的影响，具有重大的理论意义和应用价值。目前，通过过渡金属催化的C-H键活化直接来来构筑C-C、C-X键的方法，因其具有步骤短、排放的废物少、原子经济性好等优势已成为有机合成中的研究热点。本论文中重点研究了金和铁催化的sp3C-H键的活化反应，合成了一些可能具有生物活性的活性单元，为药物分子的合成寻找到一条简洁、高效的路径，并对后期的金属催化的不对称合成提供理论基础。具体研究内容包括：1.金催化的N-芳基四氢异喹啉的吲哚化吲哚是非常重要的含氮化合物，作为多功能的分子构建结构单元，在合成一些具有重要生物活性的化合物中起着非常重要的作用。近年来，人们致力于发展一条新型、环境友好、高效、高选择性的吲哚衍生物的合成方法。本文中，我们以NaAuCl4作为催化剂，过氧叔丁醇(TBHP)为氧化剂，在常温反应条件下，成功实现了N-苯基四氢异喹啉氮邻位的sp3C-H键与吲哚sp2C-H键交叉脱氢偶联，合成了一系列可能具有重要生物活性的吲哚衍生物。该方法具有高产率、高区域选择性、适用范围广泛、操作简单、条件温和等优势。2.铁催化的sp3C-H键的氧化磷酸化含磷的化合物，特别是-氨基磷酸衍生物是众多生物活性分子的前体，其中-氨基磷酸酯化合物及其相应的-氨基磷酸化合物因其与众多氨基酸结构相类似，在有机化学和药物化学上有着巨大的价值。本文中，，我们以FeCl3为催化剂，空气作为氧化剂，在温和的条件下实现了叔胺氮的邻位碳原子上sp3C-H与亚磷酸二烷基酯、部分二芳基磷氧化合物的H-P键的交叉脱氢偶联。安全、方便、环境友好、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.
【学位授予单位】：江南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5

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