【作者】 张海龙；

【导师】 裴月湖；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2004， 博士

【摘要】 以稻瘟霉分生孢子和菌丝体形态变化为活性指标，从由全球各海域采集到的400多个海洋微生物菌株(细菌、真菌和放线菌)中初步筛选出98株活性菌株。采用溶剂法和各种色谱法(硅胶柱色谱、葡聚糖凝胶柱色谱、制备薄层色谱以及HPLC等)对其中6株具有较好活性和稳定性的菌株的发酵液和／或菌丝体进行了分离。从采自黄岛的海葵上分离得到的绿1b-1号(多色曲霉Aspergillus versicolor)菌株发酵液和菌丝体中共分离得到15个化合物，并通过理化性质和波谱数据分析确定了其中12个化合物的化学结构，它们分别是：柄曲菌素(a-Ⅰ)、6-甲氧基柄曲菌素(a-Ⅱ)、奥佛尼红素(a-Ⅲ)、1，6-二甲氧基杂色曲菌素B(a-Ⅳ)、对苄氧基苯酚(a-Ⅴ)、酪氨酸(a-Ⅵ)、麦角甾-5，7，22-三烯-3β-醇(a-Ⅶ)、5α，8α-表二氧麦角甾-6，22-二烯-3β-醇(a-Ⅷ)、丁二酸(a-Ⅸ)、尿素(a-Ⅹ)、尿嘧啶(a-Ⅺ)、甘露醇(a-Ⅻ)。从采自黄岛的扇贝上分离得到的SH-3号菌(海单孢菌属Marinomonas sp.)的发酵液中共分离得到9个化合物，利用理化性质和波谱数据分析确定了其中7个化合物的化学结构，它们分别是：吡咯并哌嗪-2，5-二酮(b-Ⅰ)、3-甲基-哌嗪-2，5-二酮(b-Ⅱ)、3-甲基-吡咯并哌嗪-2，5-二酮(b-Ⅲ)、苯乙酸(b-Ⅳ)、对羟基苯乙胺(b-Ⅴ)、尿素(b-Ⅵ)、3-异丙基-吡咯并哌嗪-2，5-二酮(b-Ⅶ)；从采自珠江口海泥中分离得到的Z16—1号菌株(芽孢杆菌Bacillus sp.)的发酵液中共分离得到12个化合物，利用理化性质和波谱数据分析鉴定了其中10个化合物的化学结构，它们分别是：吡咯并哌嗪-2，5-二酮(c-Ⅰ)、3-甲基-哌嗪-2，5-二酮(c-Ⅱ)、3-羟甲基-8-羟基吡咯并哌嗪-2，5-二酮(c-Ⅲ)、胸腺嘧啶(c-Ⅳ)、3-异丁基-6-另丁基-哌嗪-2，5-二酮(c-Ⅴ)、3-异丁基-吡咯并哌嗪-2，5-二酮(c-Ⅵ)、色氨酸(c-Ⅶ)、maricyclocin(c-Ⅷ)、β-谷甾醇(c-Ⅸ)、3β-羟基-胆甾-5-烯(c-Ⅹ)；从采自烟台海星上分离得到的Z11-1号菌株(交链孢属Alternalia sp.)的发酵液中共分离得到11个化合物，利用理化性质和波谱数据分析鉴定了其中7个化合物的结构，它们分别是：(2S，3S，4R，16E)-1，4-环氧-2-[(2R)-2-羟基-十六酰胺]-16-二十六烯-1，3，4-三醇(d-Ⅰ)、(2S，3S，4R，16E)-1，4-环氧-2-[(2R)-2-羟基-十八酰胺]-16-二十六烯-1，3，4-三醇(d-Ⅱ)、(2S，3S，4R，16E)-1，4-环氧-2-[(2R)-2-羟基-十四酰胺]-16-二十六烯-1，3，4-三醇(d-Ⅲ)、丁四醇(d-Ⅳ)、曲酸(d-Ⅴ)、缬氨酸(d-Ⅵ)和3—甲基哌嗪-2，5—二酮(d-Ⅶ)；从采自南海海绵上分离得到的O2AZ-Z2号菌株(青霉属Pennicillium sp.)的发酵液中共分离得到8个化合物，利更多还原

【Abstract】 Over 400 marine microorganism strains were collected and isolated from sea area all over the world. With morphological change of Pyricularia oryzae as active index, 98 active strains of them were screened preliminarily, 6 strains of which were found to have better activities. We studied on the chemical constituents of the fermentation and/or mycelia of these six strains by all kinds of chromatographical techniques (such as silica gel chromatography. sephadex LH-20, PTLC and HPLC etc.) with bioactivity-guided fractionation. 1(?) Compounds were isolated from strain 1b-1 (Aspergillus versicolor) and determined by means of physicochemical evidences and spectral methods. These 14 compounds were identified as sterigmatocystin (a-I), 6-methoxysterigmatocystin (a-II). averufin (a-III) 1,6-dimethoxylversicolorin B (a-IV), p-benzyloxy-phenol (a-V), tyrosine (a-VI), ergosta-5, 7, 22-triene-3β -ol (a-VII), 5α, 8α-epidioxy ergosta-6, 22-diene-3β-ol (a-VIII), amber acid (a-IX), carbamide (a-X), uracil (a-XI), mannitol (a-XII). 9 Compounds were isolated from strain SH-3 (Marinomonas sp.), and 7 of which were elucicated by use of physicochemical evidences and spectral methods. These 7 compounds were identified as pyrrolopiperazine-2, 5-dione (b-I), 3-methyl piperazine-2, 5-dione (b-II), 3-methyl-pyrro(?)piperazine-2, 5-dione (b-III), phenylacetic acid (b-IV), tyramine (b-V). carbamide (b-VI), 3-isopropyl-pyrrolopiperazine-2, 5-dione (b-VII). 12 Compounds were isolated from s(?)rain Z16-1 (Bacillus sp.), and 10 of which were elucidated by using physicochemical evidences and spectral methods. These 10 compounds were identified as pyrrolopiperazine-2, 5-dione (c-I), 3-methylpiperazine-2, 5-dione (c-II). 3-hydroxymethyl-8—hydroxyl pyrrolopiperazine -2,5-dione (c-III), thymine (c-IV), 3 -isobutyl — 6—se(?)butyl-piperazine-2, 5-dione (c-V), 3-isobutyl-pyrrolopiperazine-2, 5-dione (c-VI), tryptophan (c-VII), maricyclocin (c-VIII) ,β-sitosterol (c-IX), 3β-hydroxxy-cholesta -5- ene (c-X). 1(?) Compounds were isolated from strain Z11-1(Alternaria sp.), and 7 of which were elucidate(?) by use of physicochemical evidences and spectral methods. These 7 compounds v. re identified as (2S, 3S, 4R, 16E)-1,4-epoxy-2-[(2R)-2-hydroxy hexadecanoyla(?)no]-16- hexacosene-1, 3, 4-triol (d-I), (2S, 3S, 4R.更多还原