【作者】 陶波；

【导师】 齐昌兴；

【作者基本信息】 华中科技大学 ， 药学， 2024， 硕士

【摘要】 本论文分为两章,第一章详细介绍了川鄂金丝桃（Hypericum wilsonii N.Robson）的次生代谢产物成分及其活性研究。第二章综述了2018至2024年间具有显著活性的多环多异戊烯基间苯三酚衍生物（polycyclic polyprenylated acylphloroglucinols,PPAPs）的研究情况。对采自湖北十堰地区的川鄂金丝桃的地上部分进行干燥切割处理后,用乙醇提取得到总膏。用二氯甲烷进行萃取,得二氯甲烷部分。对二氯甲烷部分总膏综合运用正相硅胶柱层析、Sephadex LH-20凝胶柱、中压反相柱、HPLC等方法进行分离纯化,得到单体化合物。通过核磁共振波谱法（Nuclear Magnetic Resonance Spectroscopy,NMR）、高分辨质谱（High Resolution Electrospray Ionization Mass Spectroscopy,HRESIMS）、电子圆二色谱（Electronic Circular Dichroism,ECD）、红外（IR）、紫外（UV）、X-ray单晶衍射、计算化学等方法确定了单体化合物的结构。此次研究共计分离鉴定了73个PPAPs,包括36个新的化合物,含2个新骨架化合物。此外,对所有化合物的免疫抑制活性,抗缺氧损伤活性,抗炎活性等进行了筛选。研究发现,化合物5和21具有明显的免疫抑制体外活性,进一步研究了化合物5的体内活性,发现化合物5具有治疗自身免疫性肝炎（Autoimmune hepatitis,AIH）的活性;化合物hypersampsone O（26）具有抗缺氧损伤活性,进一步研究了其体内活性,发现其具有治疗肝缺血再灌注损伤（Liver ischemia-reperfusion injury,HIRI）的活性,这是第一个发现的具有抗缺氧损伤活性的类金刚烷型的PPAP,也是第一个发现的具有治疗疗肝缺血再灌注损伤活性的PPAP;化合物hyperacmosin G（27）具有体外抗炎活性,其IC₅₀为4.35±1.15μM。本文对川鄂金丝桃的次生代谢产物结构及其活性进行了研究,鉴定了部分新的PPAPs类化合物,丰富了PPAPs的结构类型,并为新型抗肝脏缺血再灌注损伤药物及自身免疫性肝炎药物研发提供潜在的先导化合物。更多还原

【Abstract】 This paper is divided into two chapters.A detailed introduction to the composition and activity of secondary metabolites from Hypericum wilsonii N.Robson is provided in the first chapter.An overview of the research on PPAPs with significant activity from 2018 to 2024 is provided in the second chapter.The aboveground parts of Hypericum wilsonii N.Robson collected from Shiyan were dried and cut,and then extracted with ethanol to obtain the crude extract,which was extracted with dichloromethane to obtain the dichloromethane portion.The dichloromethane portion was separated and purified by normal silica gel column chromatography,medium pressure reversed phase column,Sephadex LH-20 gel column,High Performance Liquid Chromatography（HPLC）and other methods to obtain the monomer compound.The structures of these monomer compounds were determined through methods such as Nuclear Magnetic Resonance（NMR）Spectroscopy,High Resolution Electron Spray Ionization Mass Spectroscopy（HRESIMS）,Electronic Circular Dichroism（ECD）,Infrared（IR）,Ultraviolet（UV）,X-ray Single Crystal Diffraction,and Computational Chemistry.In this study,73 polycyclic polyprenylated acylphloroglucinols（PPAPs）were isolated and identified,including 36 new compounds（including 2 new skeleton compounds）.In addition,all compounds were screened for their immunosuppressive activity,antioxidant activity and anti-inflammatory activity,etc.Compounds 5 and 21 exhibit significant immunosuppressive in vitro activity.Further investigation into the in vivo activity of compound 5 revealed that it has good therapeutic activity for autoimmune hepatitis（AIH）;Hypersampsone O（26）has good antioxidant activity,and further research on its in vivo activity revealed that it has very good therapeutic activity for liver ischemia-reperfusion injury（HIRI）.It’s the first discovered homoadmantane-type PPAP with antioxidant activity,and also the first discovered PPAP with therapeutic activity for liver ischemia-reperfusion injury;Hyperacmosin G（27）exhibites good in vitro anti-inflammatory activity,with an IC₅₀ of 4.35±1.15μM.This article studied the structures and activity of secondary metabolites from Hypericum wilsonii N.Robson,identified some new PPAPs compounds,enriched the structural types of PPAPs,and provided potential lead compounds for the development of new anti liver ischemia-reperfusion injury drugs and autoimmune hepatitis drugs.更多还原