炭球菌素全合成和四种云南高等真菌化学成分研究
其他题名Total Synthesis of Concentricolide and Studies on the Chemical Constituents of Four Higher Fungi in Yunnan Province
房立真
学位类型博士
导师刘吉开
2008-05-28
学位授予单位中国科学院昆明植物研究所
学位授予地点昆明植物研究所
学位专业植物学
关键词炭球菌素 6-氢-1 7-二氧环戊二烯并[e]茚-8-酮 苯并呋喃酮内酯 全合成 高等真菌
摘要炭球菌素(Concentricolide)是从高等真菌炭球菌(Daldinia concentrica)中分离得到的一种结构新颖的化合物。其具有显著的抗HIV病毒活性(EC50 0.31µg/ml),可以有效地阻断HIV-1病毒结合和进入细胞,抑制HIV病毒复制,显示出较强的阻断融合活性,能降低免疫系统被损害的速度。作为小分子化合物,其细胞毒性低,体外抗HIV-1的活性显著,选择指数S.I. =222,全合成炭球菌素并进一步研究其药理活性对于发现新型治疗艾滋病的药物具有十分重要的意义。 本论文第一部分综述了炭球菌素母体结构6-氢-1,7-二氧环戊二烯并[E]茚-8-酮的合成以及苯并呋喃和γ-乙基苯并呋喃酮内酯的构建方法。尝试了两种以完全不同的起始原料为出发点的炭球菌素全合成路线。其中以3-乙烯基呋喃和γ-内酯为原料,通过Diels-Alder反应的路线已首次完成了炭球菌素的消旋全合成(Scheme 1)。另一条路线中以环己酮2-羰基乙酯为起始原料,完成了γ-乙基呋喃酮内酯官能团的构建,并得到了该条反应路线中最关键的中间体:5-Ethyl-8-oxabicyclo[4.3.0]non-1-ene-3,9-dione, 最终目标产物的合成正在进行中。这条合成路线也为合成其他具有苯并呋喃酮内酯类的活性天然产物提供了一条新的途径。论文中还设计了炭球菌素的不对称合成路线。 本论文第二部分研究了四种云南野生高等真菌的化学成分,利用多种分离手段和材料分离得到了60多个化合物,并借助现代波谱技术鉴定了其中43个化合物,包括4个新化合物。从中药竹黄中分离得到的结构新颖的苝醌类化合物hypocrellin D,该化合物具有良好的光动力活性和细胞毒活性;从红汁乳菇中分离得到了结构新颖的愈创木烷型倍半萜。
其他摘要Concentricolide, a new carbon skeleton compound isolated from the higher fungus Daldinia concentrica, was found to show significant anti-HIV bioactivity (EC50 0.31µg/ml). It inhibits the fusion of HIV-1 with normal cells and represses the replication of the virus as well as slows down the injuried speed of immune system. As a small molecular with high selection index (222) but low cytotoxicity, total synthesis of concentricolide and further investigations on its pharmacological activity are undoubtedly important to find new medcines for treatment of AIDS. The total synthesis of basic concentricolide skeleton (6H-1,7-dioxa-as-indacen-8-one) and prepared methods of benofuran and phthalide were included in the part one of this dissertation. Two pathways of total synthesis of concentricolid were performed using different starting materials, they were furan-3-carbaldehyde and γ-caprolactone, and 2-cyclohexanone carboxylate, respectively. The first total synthesis of racemic concentricolide has been achieved via Diels-Alder reaction starting from furan-3-carbaldehyde and γ-caprolactone (Scheme 1). In the meantime, prepared method of phthalide via radical addition reaction from the ethyl 2-cyclohexanone carboxylate as starting compound to the final target molecular has been established in the first time (Scheme 2). The key intermediate of this pathway 5-Ethyl-8-oxabicyclo [4.3.0] non-1-ene-3, 9-dione has been obtained too. This method can be applied to synthesize many natural bioactive phthalides with similar structures. Finally, the asymmetric synthesis of concentricolid was also designed in the dissertation. The chemical constituents of four fungi and fermentation broth collected from Yunnan province were studied as another part of this dissertation. More than sixty compounds were obtained by various chromatography methods and the structures of 43 compounds including 4 new compounds were elucidated on the basis of spectroscopic analysis. Hypocrellin D (Fig.1), type of perylenequinone compounds isolated from Chinese traditional medicine Shiraia bambusicola, showed potent cytotoxicity against Bel-7721, A-549 and Anip-973 cell lines (IC50=1.8, 8.8, 38.4µg/ml, respectively). The new sesquiterpenes (Fig.2) were also isolated from Lactarius hatsudake which belonged to guaianolides had not been reported before.
页数152
语种中文
文献类型学位论文
条目标识符http://ir.kib.ac.cn/handle/151853/240
专题昆明植物所硕博研究生毕业学位论文
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房立真. 炭球菌素全合成和四种云南高等真菌化学成分研究[D]. 昆明植物研究所. 中国科学院昆明植物研究所,2008.
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