N-甲基吡哆醛催化甘氨酸肽对亚胺的不对称加成

发布时间：2018-03-07 05:11

本文选题：N-甲基吡哆醛　切入点：α　出处：《上海师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：α,β-二氨基酸及其衍生物以其较好的生物活性在医药及生物化学方向上都有广泛应用。虽然合成α,β-二氨基酸及其衍生物的方法已经报道了很多,但是发展更高效、环境友好的α,β-二氨基酸及其衍生物的合成方法仍然极具挑战性。在生物体内,温和的条件下甘氨酸可以在基于aldol酶的维生素B6催化下直接对醛进行aldol加成得到β-羟基α-氨基酸。受此启发,我们发展了一系列手性N-甲基吡哆醛催化剂,并且成功将其用于催化甘氨酸二肽对亚胺的不对称Mannich加成反应,从而得到各种α,β-二氨基酸二肽衍生物。该反应有很好的收率和ee值,并且具有一定得非对映选择性。本文的主要工作包括一下四个方面:(1)设计并发展了一系列具有不同侧链的轴手性联芳骨架N-甲基吡哆醛催化剂,并成功实现了该类催化剂催化甘氨酸二肽对亚胺的不对称加成反应。(2)使用最佳催化剂对该反应进行条件优化,其中包括对溶剂、溶剂与水的比例、温度、添加剂种类及其当量、底物浓度及其当量比、甘氨酸肽底物等进行了筛选。(3)在最优反应条件下对亚胺进行了底物拓展得到一系列不同的α,β-二氨基酸二肽衍生物,其中反应收率在48%-91%之间,主产物ee值高达99%。(4)对N-甲基吡哆醛催化甘氨酸二肽对亚胺的不对称Mannich加成反应提出可能的反应机理。
[Abstract]:伪, 尾 -diamino acids and their derivatives have been widely used in medicine and biochemistry because of their good biological activities. Although many methods of synthesizing 伪, 尾 -diamino acids and their derivatives have been reported, they have been developed more efficiently. The synthesis of environmentally friendly 伪, 尾 -diamino acids and their derivatives remains extremely challenging. A series of chiral N-methylpyridoxal catalysts were developed under mild conditions in which glycine can be directly added to aldehydes by aldol addition under the catalysis of vitamin B _ 6 based on aldol enzyme, so we have developed a series of chiral N-methylpyridoxal catalysts. It has been successfully used to catalyze the asymmetric Mannich addition reaction of glycine dipeptide to imine and to obtain various 伪, 尾 -diamino acid dipeptide derivatives. The main work of this paper includes four aspects: design and development of a series of chiral N-methylpyridoxal catalysts with different side chains. The asymmetric addition reaction of glycine dipeptide to imine catalyzed by this kind of catalyst was successfully realized. The optimum catalyst was used to optimize the reaction conditions, including solvent, solvent to water ratio, temperature, additive type and its equivalent. A series of 伪, 尾 -diamino acid dipeptide derivatives were obtained under the optimum reaction conditions by screening the substrate concentration and its equivalent ratio, glycine peptide substrate and so on. The yield of the reaction was between 48% and 91%. The EE value of the main product was as high as 99 / 4). The possible mechanism of the asymmetric Mannich addition of glycine dipeptide to imine catalyzed by N-methylpyridoxal was suggested.
【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251

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