【作者】 张婷；

【导师】 李景华；

【作者基本信息】 浙江工业大学 ， 药物化学， 2010， 硕士

【摘要】 本文共分为四章,其中第一章主要讲述了无溶剂反应的种类,并对其中的固相机械研磨法进行了概括,阐述其影响因素,对机械研磨法在有机合成中的应用进行了概述,同时分析了其应用优势及发展前景。第二章阐述了γ-氨基丁酸(GABA)以及其衍生物的生理功能、药物应用价值以及以5-亚烃基米氏酸与硝基烷烃类化合物在固相机械研磨条件下进行Michael加成合成γ-氨基丁酸衍生物的前体。GABA类化合物对哺乳动物神经中枢具有一定调节作用,在医药方面应用广泛。反应在以CH3ONa作为缚酸剂的条件下,机械研磨合成,反应条件温和,时间短,选择性好,收率高。与传统路线相比,反应过程中不使用溶剂,减少环境污染,降低生产成本,为γ-氨基丁酸衍生物的前体的合成提供了一条绿色高效的工艺路线。第三章讲述了氨基酸类化合物具有重要的生理功能以及广泛的应用价值。阐述了氨基酸与1,3-二羰基化合物的固相缩合反应,反应生成氨基酸类似化合物。其中温度为反应控制的重要因素,操作简单,时间短,收率高。由上可知,固相机械研磨法高效,绿色,操作简单,对于药物合成工业很有价值。更多还原

【Abstract】 This dissertation consists of four chapters. The Chapter one is a review of research progress on the solid-state mechanochemistry in organic synthesis. It is reported factors of solid-phase mechanochemistry, reaction mechanism, as well as their applications in pharmaceutical industry. Close attention has also been paid to the prospects of the applications and perspective.In the Chapter two, we describe the physiological function of GABAs, as well as its value . GABA is nonprotein amino acid which has been identified as the nerve center of a mammalian inhibitory neurotransmitter. It is an important intermediate of drugs. In this paper, a facile Michael addition reaction of 5-alkylidene Meldrum’s Acid with nitroalkanes in solid state has been achieved by mechanochemical grinding in the presence of CH3ONa. The reactions proceed smoothly under solvent-free condition and give their corresponding results in high yields. The method is more efficient and green as compared to prior arts.In the Chapter three, a method of mechanochemical grinding is used in the condensation of amino acids with 1,3-dicarbonyl compounds in the present of KOH. This rout provide a simple manipulation, efficient, time-saving way for synthesizing derivatives of amino acids.In conclusion, the method of mechanochemical grinding, which might be useful for preparing drugs, has the advantage of efficiency, “green”, simple manipulation, mild conditions. It might be valuable to the pharmaceutical industry.更多还原