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题名	高等真菌化学成分的结构多样性研究
作者	邵红军
学位类别	博士
答辩日期	2005-05-31
授予单位	中国科学院昆明植物研究所
授予地点	昆明植物研究所
导师	刘吉开
关键词	高等真菌 化学成分 结构多样性 抗真菌活性
其他题名	Study on Chemical Diversity of Mycrofungi
学位专业	植物学
中文摘要	高等真菌属于“高创造系数”的生物资源之一，其所含次生代谢产物的化学结构多样且新颖。这种化学结构多样性对于药物和农药先导化合物的发现至关重要。云南是世界上生物多样性研究的热点地区之一，蕴藏着丰富的高等真菌资源，高等真菌不仅种类繁多，而且一种真菌可能有多个菌株。这些种类和菌株的多样性无疑为该区高等真菌产生丰富多样的次生代谢产物提供了天然的物质基础。此外，与植物不同的是高等真菌可发酵培养，对可培养真菌的同一菌株而言，通过改变培养条件，它们可能产生更多类型或数量的次生代谢产物，即one strain-many compounds（OSMAC）。这也无疑是一条发掘可培养高等真菌化学成分多样性的有效途径。为研究云南高等真菌的化学多样性，以期发现具有生理活性的先导化合物，本论文研究了12种云南野生高等真菌发酵液和子实体的化学成分。这些材料包括炭球菌（Daldinia concentrica）、长柄炭角菌（Xylaria longipes）、西澳粘滑菇（Hebeloma westraliense）、松杉暗孔菌（Phaeolus schweinitzii）、伯氏圆孢地花(Bondarzewia berkeleyi)、硬皮地星（Astraeus hygrometricus）和浅黄根须腹菌（Rhizopogon luteolus）等7种发酵液；以及黄滑锈伞（Hebeloma versipelle）、绒边乳菇（Lactarius pubescens）、褪色红菇(Russula decolorans)、锈盖粉孢牛肝菌（Tylopilus ballouii）和放射纤孔菌（Inonotus radiatus）等5种子实体。利用多种分离手段和波谱技术分离并鉴定了106个化合物，包括72不同的化合物，其中12个新化合物。化合物结构类型涉及炭球菌素、倍半萜、三萜、松苞菌素、甾体、脑苷酯、含氮化合物、蒽醌、环戊酮和取代苯等。此外，对采自云南地区的60种高等真菌子实体抑制农业病原真菌的活性进行了测试，筛选出地花菌（Albatrellus dispansus）和炭球菌（D. concentrica）2种样品对供试真菌表现出强抑制作用；在活性追踪的指导下从地花菌中分离得到具有显著离、活体活性成分grifolin。 第一章 炭球菌和长柄炭角菌的化学成分研究 通过改变培养容器和培养基装量，从炭球菌（D. concentrica）发酵液中分离得到20个化合物，其中6个为新化合物，分别是4个灰孢菌素类倍半萜（1-4）和2个炭球菌素类化合物（11-12）。这类倍半萜系首次从该属真菌中分离得到，化合物4是一个很少见的降一灰孢菌素类倍半萜。从长柄炭角菌（X. longipes）发酵液中分离出5个已知化合物。 第二章 黄滑锈伞和西澳粘滑菇的化学成分研究 从黄滑锈伞（H. versipelle）子实体中分离鉴定了1个新的具有细胞毒活性的羊毛甾烷型三萜，即24(E)-3β-hydroxylanosta-8,24-dien-26-al-21-oic acid (1)，以及其它11个已知化合物。该三萜对4种肿瘤细胞株有中等抑制作用，其IC50在10-25.0 μg/ml之间。从同属真菌西澳粘滑菇（H. westraliense）发酵液中分离得到了6个已知化合物，其中化合物15（volemolide）是一高度降解的甾醇，首次发现存在于丝膜菌科。 第三章 绒边乳菇和褪色红菇的化学成分研究 在对绒边乳菇（L. pubescens）化学成分研究过程中，分离鉴定了6个化合物，包括1个新的小皮伞烷型倍半萜（1）；而从褪色红菇(R. decolorans)中得到了9个已知化合物。 第四章 松杉暗孔菌、伯氏圆孢多孔菌和放射纤孔菌的化学成分研究 多孔菌科真菌含有多种结构新颖且生物活性显著的次生代谢产物。我们对3种该科真菌（松杉暗孔菌、伯氏圆孢多孔菌和放射纤孔菌）的化学成分进行了研究，共得到18个化合物，包括2个新化合物。从松杉暗孔菌（P. schweinitzii）和伯氏圆孢多孔菌（B. berkeleyi）2种发酵液中分别分离并鉴定了8个化合物。其中(3R)-5-hydroxymellein-α-D-glucopyranoside (5)是从松杉暗孔菌中得到的新化合物，而从伯氏圆孢多孔菌中发现了1个新的二氢苯并呋喃类化合物（9）；而从放射纤孔菌（I. radiatus）的子实体中分得5个已知化合物。 第五章 硬皮地星的化学成分研究 从硬皮地星（A. hygrometricus）发酵液中分离鉴定了8个化合物，其中化合物1是一新的多羟基甾醇酯。 第六章 浅黄根须腹菌的化学成分研究 在浅黄根须腹菌（R. luteolus）发酵液中发现了1个新的环戊酮类化合物（7）和7个已知化合物。 第七章 锈盖粉孢牛肝菌的化学成分研究 从锈盖粉孢牛肝菌（T. ballouii）的子实体中共得到了11个已知化合物。 第八章 60种高等真菌的农用抗真菌活性研究 在高等真菌子实体提取物样品供试质量浓度为0.1 g/mL下，用琼胶平板法测定了60种高等真菌样品乙醇提取物对9种植物病原真菌菌丝生长的抑制作用。结果表明，地花菌和炭球菌2种样品对供试真菌表现出强抑制作用，其中地花菌对油菜菌核（Sclerotinina sclerotiorum）和小麦赤霉（Fusarium graminearum）2种病原真菌菌丝生长可完全抑制。在活性追踪的指导下，从该高等真菌中分离鉴定了活性化合物grifolin。离体条件下，该单体化合物在供试浓度为304.9 μm时，对油菜菌核（S. sclerotiorum）和小麦赤霉（F. graminearum）2种病原真菌菌丝生长的抑制率分别为86.4%和80.9%，而在供试浓度为38.1 μm时，grifolin可完全抑制小麦赤霉（F. graminearum）、苹果炭疽（Gloeosporium fructigenum）和水稻稻瘟（Pyricularia oryzae）等3种病原真菌的孢子萌发；盆栽实验结果表明，在施药浓度为304.9 μm时，8天后grifolin对小麦白粉（E. graminis）的防治效果可达到65.5%，与对照药剂效果相当。 第九章 综述：OSMAC-发掘微生物次生代谢产物多样性的有效途径 本章就OSMAC方法的理论依据和实践进行了初步总结。
英文摘要	Higher fungi continue to offer an unique and renewable resource for the discovery of potential new drugs and biological entities because of the chemical and biological diversity of their secondary metabolites. Yunnan Province, as one of the hotspots for biodiversity, is a rich region for higher fungi. On the other hand, many higher fungi can be fermented, and a single strain often has the potential to produce more various compounds in different cultivation conditions (one strain-many compounds, OSMAC). As an important part of our works on searching for secondary metabolites with unique chemical and biological diversity from higher fungi in Yunnan Province, the chemical constituents of twelve higher fungi were studied. Those fungi included Daldinia concentrica, Phaeolus schweinitzii, Rhizopogon luteolus, Astraeus hygrometricus, Bondarzewia berkeleyi, Xylaria longipes, Hebeloma westraliense, Hebeloma.versipelle, Lactarius pubescens, Russula decolorans, Tylopilus ballouii, and Inonotus radiatus. 106 compounds have been obtained by chromatographic methods, among which, 72 different compounds were elucidated on the basis of spectroscopic data including 12 new ones. Chapter 1: Chemical investigation of D. concentrica and X. longipes Twenty compounds were isolated and identified from the culture broth of D. concentrica by OSMAC approach. Among them, six were new ones, including four botrydial sesquiterpenoids (1-4) and two concentricolide derivates (11-12). Those botrydial sesquiterpenoids were obtained for the first time from the genus Daldinia, and compound 4 was a rare nor-sesquiterpenoid aldehyde. Five known compounds were also isolated from the culture broth of X. longipes. Chapter 2: Chemical investigation of H. versipelle and H. westraliense A new cytotoxic lanostane triterpenoid, 24(E)-3β-hydroxylanosta-8,24-dien-26- al-21-oic acid (1), together with eleven known compounds, were obtained from the fruiting bodies of H. versipelle. The compound 1 moderately inhibited the growth of four tumor cell lines (IC50 10-25.0 μg/ml). Six known compounds were also isolated from the culture broth of H. westraliense, and volemolide (15), a norsterol, has been found in the Cortinariaceae for the first time. Chapter 3: Chemical investigation of L. pubescens and R. decolorans Phytochemical study of the fruiting bodies of L. pubescens has resulted in the isolation of six compounds, including a new marasmane sesquiterpenoid. From the fruiting bodies of R. decolorans, nine known compounds were isolated and identified. Chapter 4: Chemical investigation of P. schweinitzii, B. berkeleyi and I. radiatus Mushroom belonging to Polyporaceae were rich in secondary metabolites, which with a variety of biological activities. During our phytochemical study of three species of Polyporaceae, eighteen compounds, including two new ones, were gained and identified by spectroscopic analysis. Among them, eight compounds have been obtained and elucidated from liquid culture of P. schweinitzii and B. berkeleyi, respectively. (3R)-5- hydroxymellein-α-D-glucopyranoside (5) was a new one from P. schweinitzii, and compound 9 was a new dihydrobenzofuran cyclopentenone from B. berkeleyi, and five known compounds were also obtained from the fruit bodies of I. radiatu. Chapter 5: Chemical investigation of A. hygrometricus The culture broth of A. hygrometricus has afforded a new naturally occurring polyhydroxylated steryl ester (1) and seven other known compounds. Chapter 6: Chemical investigation of R. luteolus A new cyclopentenone (7) has been found in the culture broth of R. luteolus, along with seven known compounds, and their structures were assigned by means of spectroscopic methods. Chapter 7: Chemical investigation of T. ballouii In this work, twelve known compounds were obtained from the fruit bodies of T. ballouii. Chapter 8: Screening for antifungal activities of sixty higher fungi Ethanol extracts of sixty higher fungi collected in Yunnan Province were subjected to screening for antifungal activity, using the poison food technique against several plant pathogenic fungi. Of the extracts tested, those of A. dispansus and D. concentrica exhibited considerable activities, and it was found that the extract of A. dispansus almost completely inhibited mycelial growth of S. sclerotiorum and F. graminearum S. Grifolin, the active compound, was isolated from the fruiting bodies of A. dispansus by bioassay-guided fractionation, and its antifungal activities were evaluated in vitro against nine plant pathogenic fungi and in vivo against E. graminis. In vitro, grifolin inhibited mycelial growth of S. sclerotiorum and F. graminearum with inhibition of 86.4 and 80.9% at 304.9 μm, respectively, and completely inhibited spore germination of F. graminearum, G. fructigenum and P. oryzae at 38.1 μm. In vivo, the curative effect of grifolin against E. graminis was 65.5% at 304.9 μm after 8 days. Chapter 9: OSMAC-an efficient approach to exploit the secondary metabolites diversity of microorganism This chapter summarized the concept and foundation of OSMAC, and several examples using this method were also presented.
语种	中文
公开日期	2011-10-25
页码	150
内容类型	学位论文
源URL	[http://ir.kib.ac.cn/handle/151853/146]
专题	昆明植物研究所_昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	邵红军. 高等真菌化学成分的结构多样性研究[D]. 昆明植物研究所. 中国科学院昆明植物研究所. 2005.

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