海洋红藻多管藻和松节藻的化学成分及抗氧化活性研究

IOCAS-IR > 海洋环流与波动重点实验室

	海洋红藻多管藻和松节藻的化学成分及抗氧化活性研究
	李可
学位类型	博士
导师	王斌贵
	2008-05-23
学位授予单位	中国科学院海洋研究所
学位授予地点	海洋研究所
学位专业	海洋药物学
关键词	海藻多管藻松节藻化学成分溴酚自由基清除活性
摘要	海洋生物具有产生丰富多样的次生代谢产物的能力，其中红藻门松节藻科海藻卤代次生代谢产物以其结构新颖、生物活性独特引起了天然产物化学家的重视。本论文对海洋红藻多管藻和松节藻进行了化学成分研究，综合利用各种色谱学方法 (硅胶柱层析、反相硅胶柱层析、凝胶Sephadex LH-20柱层析、半制备高效液相色谱以及重结晶等) 和现代波谱学技术 (IR、UV、EI-MS、FAB-MS、HR-ESI-MS、CD、1H-NMR、13C-NMR、DEPT、1H-1H COSY、HSQC、HMBC等)，共分离鉴定了100个化合物，发现25个新化合物。从多管藻中分离鉴定38个化合物 (24个溴酚化合物)，其中7个新化合物 (均为溴酚化合物)，包括1个菲并呋喃结构溴酚 (P1), 2个二氢菲结构溴酚 (P2, P3)，1个含 5,7-dihydrodibenzo[c,e]oxepine 结构溴酚 (P4)和3个简单溴酚 (P5, P6, P7)。P1 (urceolatin) 属首例报道的具有菲并呋喃结构的天然产物，从该种中分离的化合物P12 和 P13 可能是其生源合成的前体。P2和P3为第二例报道的具有二氢菲结构的溴酚化合物。从松节藻中分离并鉴定了62 个化合物，其中18 个为溴酚类新化合物，44 个为已知化合物。化合物具有多变的取代基团，包括2 个脲基吡咯烷酮溴酚化合物 (R1, R2), 4 个γ-脲基丁酸溴酚化合物 (R3-R6)，5 个酰胺溴酚化合物 (R7, R8, R9, R13, R14)，1 个溴酚砜化合物 (R12), 1 个Xanthene 溴酚化合物 (R10)和5 个简单溴酚化合物 (R11, R15, R16, R17, R18)。R1、R2 是首例报道的含有脲基吡咯烷酮片段的天然产物，R10 为首次报道的溴代Xanthene 类天然产物。对分离到的化合物进行了清除DPPH 和ABTS两种自由基活性的筛选。结果发现溴酚类天然产物具有显著的DPPH自由基清除活性，其中R3 的IC50 仅为3.3 μM, 其活性强度约为阳性对照BHT (IC50 为82.1 μM) 的24倍。另外，溴酚类天然产物对ABTS自由基有较强的清除活性，R2 的TEAC（Trolox efficency activity capacity）值为5.2 mM，约为阳性对照 (ascorbic acid, 1.02 mM) 的 5 倍。初步的构效关系研究发现，稠环分子、多羟基和邻位甲氧基等结构特点能有效增强DPPH 自由基清除活性；特殊取代基如脲基、吡咯烷酮等含有氮原子的基团，能有效增强ABTS 自由基清除活性，多羟基、溴代等结构特点也使其活性有所增强。本研究结果丰富了海藻卤代化合物的结构类型，为多管藻和松节藻的合理利用提供了一定的科学依据。
其他摘要	Marine organisms have ability to produce structurally interesting and biologically active secondary metabolites. In recent years, natural product chemists have paid more and more attention to the halogenated secondary metabolites from marine red algae of Rhodomelaceae family. In the present dissertation, the structures of 100 compounds were characterized from two Rhodomelaceae species of Polysiphonia urceolata and Rhodomela confervoides. The separation was performed by repeated column chromatography (CC) on silica gel, RP-18, Sephadex LH-20, and semi-preparative HPLC. The structures of the isolated compounds were elucidated by spectroscopic analysis including IR, UV, EI-MS, FAB-MS, HR-ESI-MS, CD, 1D-NMR (1H-NMR, 13C-NMR, DEPT) and 2D-NMR (1H-1H COSY, HSQC, HMBC). From the extracts of P. urceolata, a total of 38 compounds were isolated and structurally elucidated. Among them, 7 bromophenols were found to be new structures (P1-P7) with one compound (urceolatin, P1) possessing a previously not reported phenanthro[4,5-bcd]-furan moiety in natural products. From a biogenetic point of view, P1 is likely generated by intermolecular free radical reactions involving two molecules P12 and P13, which were also isolated from P. urceolata. P2 and P3 possess a 9, 10-dihydrophenanthrene skeleton and this is only the second example of such kind of compounds isolated from a marine source, while P4 possesses an unusual 5,7-dihydrodibenzo[c, e]oxepine structural moiety. From the extracts of R. confervoides, a total of 62 compounds were isolated and structurally elucidated. Among them, 18 bromophenols were found to be new chemicals (R1-R18). Of these compounds, R1 and R2 possess oxopyrrolidin-ureido structural unit, while R3-R6 possess γ- ureidobutanoic acid moiety. In addition, five bromophenols (R7, R8, R9, R13, and R14) possess amino-4-oxobutanoic acid units. The other new compounds including one methylsulfonylmethyl bromophenol (R12), one xanthene derivatives bromophenol (R10), and five simple bromophenols (R11, R15, R16, R17, R18). To the best of our knowledge, this is the first report of natural products containing ureido-pyrrolidinone moiety (R1 and R2), while R10 is the first example of a bromo-xanthene natural derivative. Radical scavenging activities of the isolated compounds were evaluated by scavenging DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical assay and ABTS (2,2'-Azinobis-(3- ethylbenzothiazoline-6-sulfonic acid)diammonium salt) radical assay. In general, bromophenols displayed scavenging activity in various degrees with R3 displayed significant DPPH radical-scavenging activity (IC50 value 3.3 μM) which is 24-fold more potent than positive control BHT (IC50 82.1 μM). R2 showed moderate ABTS free radical-scavenging activitiy with a TEAC = 5.2 mM, which is 5-fold potent than positive control ascorbic acid (TEAC = 1.0 mM). Structure-activity analysis indicated that our result is in accordance with the former conclusions that the DPPH radical scavenging efficiency of monohydroxyl phenols is strongly enhanced by the introduction of second hydroxyl group and is increased by one or two methoxyl substitutions in the ortho position. Special substitutions such as ureido and pyrrolidinone had significant influence on ABTS radical scavenging activities. The bromination and polyhydroxyl are also important factors responsible for ABTS radical scavenging activities. The results from this investigation provided new entities to the marine algal derived halogenated natural products and may provide new idea for the use of P. urceolata and R. confervoides.
页数	119
语种	中文
文献类型	学位论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/439
专题	海洋环流与波动重点实验室
作者单位	中国科学院海洋研究所
推荐引用方式 GB/T 7714	李可. 海洋红藻多管藻和松节藻的化学成分及抗氧化活性研究[D]. 海洋研究所. 中国科学院海洋研究所,2008.