【作者】 唐芳；

【导师】 张勇慧；

【作者基本信息】 华中科技大学 ， 药物化学， 2012， 硕士

【摘要】 Kinsenoside（金线莲苷）和goodyeroside A是具有多种生物活性的糖苷类化合物，存在于多种植物中，两者互为差向异构体。本课题采用化学合成与酶催化相结合的方法成功合成了这一对天然产物，总产率均能达到12.7%。首先，分别以D-苹果酸和L-苹果酸为原料，经过四步化学反应合成了对映异构体苷元(R)-3-羟基-γ-丁内酯和(S)-3-羟基-γ-丁内酯，产率约为75.2%。然后，以3-羟基-γ-丁内酯和葡萄糖为底物，苦杏仁β-D-葡萄糖苷酶为催化剂，通过有机溶剂种类及其与缓冲液比例的筛选成功建立了糖苷合成的均相反应体系。再者，使用高效液相色谱和蒸发光散射检测器建立了测定kinsenoside和goodyerosideA浓度的方法。最后，对影响因素反应时间、酶用量和3-羟基-γ-丁内酯的浓度进行了单因素实验和正交实验的评价，确定了酶催化反应的最佳条件。在最优苷化反应条件下，kinsenoside和goodyeroside A的产率分别达到17%和16.8%。ZHAO330是从甘西鼠尾草中分离得到的新化合物，结构复杂，属于松香烷型二萜，在体外细胞毒实验中表现出显著的抗肿瘤活性。本课题对ZHAO330的全合成路线进行了设计，并对其中取代菲环的合成和手性侧链的引入进行了探索研究。首先以3,4-二羟基苯甲醛为原料，经过6步反应成功合成了取代菲环。然后，通过选用不同的酚羟基保护基团实现了最后菲环上羟基的选择性保护，为手性侧链的引入奠定了基础。更多还原

【Abstract】 Kinsenoside and goodyeroside A, two epimers of plant natural products withdiverse biological activities, have been synthesized efficiently by a combination ofchemical and enzymatic approaches with a total yield of12.7%. Firstly, the twoenantiomers of the aglycon,3-hydroxy-γ-butyrolactone, were prepared from D/L-malic acids by a chemical approach in a yield of75.2%within four steps. Secondly,3-hydroxy-γ-butyrolactones were successfully converted to their glycosides in thepresence of β-D-glucose by using β-D-glycosidase from almond as a catalyst in ahomogeneous organic-water system. Thirdly, a method for the determination ofkinsenoside and goodyeroside A was developed by HPLC with ELSD. Finally,single-factor and orthogonal experiments were employed to confirmed the influencesof reaction time, enzyme dosage and concentration of3-hydroxy-γ-butyrolactone onthe yield of product. Under the optimized enzymatic conditions, the yields ofkinsenoside and goodyeroside A reached17%and16.8%respectively.ZHAO330, a new compound separated from Salvia przewalskii Maxim, is acomplicated derivative of abietane type diterpene and shows significant anti-tumoractivity in vitro cytotoxicity experiment. This topic with a total synthesis routedesigned for ZHAO330has explored the synthesis of substituted phenanthrene andthe introduction of chiral lateral chain. Firstly, with3,4-dihydroxybenzaldehyde asraw materials, substituted phenanthrene was synthesized in six steps. Then, throughusing different protecting groups, phenolic hydroxyl on phenanthrene was substitutedselectively, which would lay the foundation for the synthesis of lateral chain.更多还原