芥子碱论文：拟天然产物芥子碱系列化合物的合成结构表征及其生物活性研究.docVIP

芥子碱论文：拟天然产物芥子碱系列化合物的合成、结构表征及其生物活性研究 【中文摘要】天然产物的合成研究一直是有机化学学科中最令人瞩领域。天然产物芥子碱广泛存在于白芥子、黄芥子、莱菔子、葶苈子等十字花科植物中,自然界中以芥子碱硫氰酸盐的形式存在最为广泛,其在十字花科植物的生理代谢调控、提高植物抗病性和改善植物营养品质等方面起着非常重要的作用。芥子碱具有抗氧化、抗衰老、抗辐射、降血压等生物活性,在这些药物的研究开发中有着重要作用。本文以取代的苯甲醛和丙二酸为起始原料,经Doebner-Knoevenagel缩合反应、酯化、成季铵盐得到10种中间产物,将其经离子交换反应合成10种拟天然产物芥子碱的系列化合物,所有目标产物以及部分中间产物均为未见文献报道的新化合物。利用IR、1HNMR等现代测试方法对所合成的目标产物及中间体的结构进行了表征。天然提取的芥子碱,其水溶性较差,在部分生物活性测试研究中应用受到限制,本文利用离子交换技术将芥子碱中的硫氰酸根离子替换为水溶性较好的氯离子,研究了其对家兔离体平滑肌张力收缩的作用,同时,将所合成的部分目标化合物也做相应测试,结果表明,部分目标化合物对家兔离体平滑肌有明显的舒张作用和收缩作用。以乳腺癌细胞MCF-7细胞株为模型,研究人工合成的芥子碱类似物对癌细胞的抑制作用,以目标化合物1a为例,探索了最低有效浓度和最佳作用时间点,分别配制0.25md/L,0.5 mg/L,1mg/L,2 mg/L,4 mg/L和8mg/L的终浓度,观察在24h内每种浓度下的癌细胞存活率,结果显示,部分目标化合物对乳腺癌细胞MCF-7细胞株表现出较好的抑制作用。 【英文摘要】The study of the synthesis of natural products is the most remarkable fields in organic chemistry. The natural product sinapine widely exists in crucifer such as white mustard seed, yellow mustard seed, radish seed, pepperweed seed etc, and gets together in the form of shinapine thiocyanate in the plants. The sinapine plays an important role in the control of metabolism, improvement of disease resistance in plants and the nutrition quality. The sinapine has the bioactivity of antioxygen, anti-aging, resisting radiation, falling blood pressure etc, and plays an important role in these drug research.In this paper,10 kinds of analogues of sinapine are synthesized by the reaction of Doebner-Knoevenagel condensation, esterification, getting into quaternary ammonium salt, ion exchange using substituted benzaldehyde and malonate as the starting materials.All 10 target products and the other 10 intermediates are new compounds, a total of 20 compounds are not reported, the structure of which are characterized by IR,1HNMR and the other modern test methods.The water solubility of the sinapine thiocyanate extracting from the natural plants is not good, and is not conducive to some research of activity test, so the thiocyanate ion is replaced by the chloride ion which has a good water s