奇乳海参、异常赛瓜参和乌皱辐肛参的生物活性成分研究
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摘要
奇乳海参(Holothuria axiloga),异常赛瓜参(Thyone anomala)和乌皱辐肛参(Actinopyga miliaris)为海参纲动物,在我国南海海域有着广泛的分布。本课题以稻瘟酶模型为活性追踪分离的筛选手段,应用大孔树脂、正相硅胶、反相硅胶、葡聚糖凝胶以及高效液相色谱法等多种色谱分离技术,对三种海参所含的抗肿瘤和抗真菌活性成分进行了系统的化学成分和生物活性研究。共分离得到了42个单体化合物(奇乳海参20个,异常赛瓜参6个,乌皱辐肛参16个),综合应用多种现代波谱技术和化学方法测定了42个单体化合物的化学结构。其中新化合物8个。
从奇乳海参中分离鉴定了20个三萜皂苷化合物,其化学结构鉴定如下,HA-1: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃木糖基基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8),25(26)-海参烷烯-3β-醇(stichloroside A2);HA-2: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃木糖基基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8)-海参烷烯-3β-醇(stichloroside A1);HA-3: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃木糖基基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}- 23-乙酰氧基-7(8),25(26)-海参烷烯-3β-醇(stichloroside C2) ; HA-4: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃木糖基基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8)-海参烷烯-3β-醇(stichloroside C1);HA-5: 3-O-[β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸-β-D-吡喃木糖基]-22,25-环氧-9 (11)-海参烷烯-3β,12α,17α-三醇(axilogoside A);HA-6: 3-O-[β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin B);HA-7: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1?3)-β-D-吡喃葡萄糖-(1?4)-β-D-吡喃奎诺糖-(1?2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1?3)-β-D-吡喃葡萄糖-(1?4)]-β-D-吡喃木糖}-22,25-环氧-海参烷-9 (11)-烯-3β,12α,17α-三醇(marmoroside G);HA-8: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin A);HA-9:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-3β,12α-二醇(pervicoside C);HA-10: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22-羰基-9(11)-海参烷烯-3β,12α-二醇(fuscocineroside B);HA-11: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22-羰基-25-乙酰氧基-9 (11)-海参烷烯-3β,12α-二醇(fuscocineroside A);HA-12: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9 (11)-海参烷烯-3β,12α-二醇(fuscocineroside C) ; HA-13: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-9(11),24(25)-海参烷烯-3β,12α-二醇(axilogoside C);HA-14: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-22-羟基-3β,12α,17α-三醇(holothurin A1);HA-15: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-3β,12α,17α-三醇(echinoside A);HA-16: 3-O- [(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-25-乙酰氧基-9(11)-海参烷烯-3β,12α-二醇(pervicoside A);HA-17:3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃葡萄糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8)-海参烷烯-3β-醇(axilogoside G);HA-18:3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃木糖-(1→4)-β-D-吡喃木糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-海参烷-23-乙酰氧基-7 (8)-烯-3β-醇(axilogoside B);HA-19:3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃木糖-(1→4)-β-D-吡喃葡萄糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-海参烷-23-乙酰氧基-7 (8)-烯-3β-醇(axilogoside C);HA-20:3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-海参烷-23-乙酰氧基-9 (11)-烯-3β, 12α-二醇(axilogoside H)。
从异常赛瓜参中分离鉴定的6个海参皂苷为:TA-1:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin A);TA-2:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-22-羟基-3β,12α,17α-三醇(holothurin A1);TA-3:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷-烯-3β,12α-二醇(anomaloside A);TA-4:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-3β,12α,17α-三醇(echinoside A);TA-5:3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇( holothurin B);TA-6:3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-9(11)-海参烷-3β,12α,17α-三醇(echinoside B)。还得到2个甾体类化合物。
从乌皱辐肛参中分离鉴定的12个海参皂苷为:AM-1: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-9 (11), 24 (25)-海参烷烯-3β, 12α,22-三醇(miliariside A);AM-2: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-23-乙酰氧-9 (11), 24 (25)-海参烷烯-3β, 12α, 17α-三醇(miliariside B);AM-3: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)- [(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-24-羰基-9 (11)-海参烷烯-3β, 12α-二醇(miliariside C);AM-4: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-16-乙酰氧基-9 (11), 24 (25)-海参烷烯-3β, 12α, 17α-三醇(miliariside D);AM-5: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-9(11)-海参烷烯-3β, 12α-二醇(bivittoside D);AM-6: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin A) ; AM-7: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-3β,12α,17α-三醇(echinoside A);AM-8: 3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(holothurin B);AM-9: 3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-9(11)-海参烷烯-3β,12α,17α-三醇(echinoside B);AM-10: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-9 (11), 24 (25)-海参烷烯-3β, 12α-三醇(impatenside A);AM-11: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-23-乙酰氧基-9 (11), 24 (25)-海参烷烯-3β, 12α-二醇(miliariside E);AM-12: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-25-乙酰氧基-9 (11)-海参烷烯-3β, 12α-二醇(miliariside F)。另外还得到4个甾体类化合物:AM-13: 3β-硫酸钠-5α-7(8),24-胆甾二烯, AM-14:3β-硫酸钠-24-乙基-5α-7(8)-胆甾烯,AM-15:3β-硫酸钠-5α-7(8)-胆甾烯, ,AM-16:3β-硫酸钠-5α-胆甾。
初步的药理活性筛选表明:海参皂苷对稻瘟霉显示显著的生物活性;从异常赛瓜参中分离得到的6个海参皂苷对BEL-7402人肝癌细胞、HL-60人白血病细胞、A-549人肺癌细胞和P388小鼠白血病细胞都具有细胞毒活性;所有分离得到的38个皂苷类化合物对白色念珠菌,新生隐球菌和红色毛癣菌等均具有不同强度的抑制生长作用。
本课题对三种海参的化学成分和生物活性进行的深入系统研究,为研发海洋来源的抗肿瘤和抗真菌药物提供了新的先导化合物,为开发海参的药用价值提供了科学依据,为海洋天然产物化学积累了新的研究资料,对开发我国丰富的海洋生物资源具有重要的意义。
Holothuria axiloga, Thyone anomala and Actinopyga miliaris distributed abundantly in South China Sea. Guided by Pyricularia oryzae bioassay model, the anti-cancer and anti-fungal constituents of Holothuria axiloga, Thyone anomala and Actinopyga miliaris have been investigated by various chromatography methods including LPLC, MPLC, HPLC on silica gel, ODS RP C18 and Zorbax SB C18 respectively. Forty-two compounds were isolated and structures of all the compounds were elucidated by chemical and spectral analysis (IR, EI-MS, ESI-MS, HRESI-MS, 1HNMR, 13CNMR, 1H-1H COSY, DQCOSY, TOCSY, HMQC, HMBC, NOESY, etc.).
From the ethanolic extracts of H. axiloga, twenty triterpene glycosides were isolated and the structures were identified as the below, HA-1:3-O-{(3-O-methyl-β-D-glucopyra nosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-xylopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8),25(26)-holostene-3β-ol(stichlorosideA2);HA-2:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-xylopyranosyl-(1→2)-[(3-O-methyl-β-D-glucop-yranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-hol-ostene-3β-ol(stichlorosideA1);HA-3:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8),25(26)-holo-stene-3β-ol(stichlorosideC2);HA-4:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-holostene-3β-ol(stichlorosideC1);HA-5:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sulfo-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(axilogosideA);HA-6:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(holothurinB);HA-7:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyran-osyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(marmorosideG);HA-8:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(holothurinA);HA-9:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-9(11)-holostene-3β,12α-diol(pervicosideC);HA-10:3-O-[(3-O-methyl- β-D-glucopyranosyl)-(1→3)-β-D-glu-copyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22-one-9(11)-holostene-3β,12α-diol(fuscocinerosideB);HA-11:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22-one-25-acetoxy-9(11)-holostene-3β,12α-diol(fuscocinerosideA);HA-12:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α-diol(fuscocinerosideC);HA-13:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α-diol(axilogosideC);HA-14:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylop-yranosyl]-9(11)-holostene-3β,12α,17α,22-tetrol(holothurinA1);HA-15:3-O-[(3-O-me-thyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-9(11)-holostene-3β,12α,7α-triol(echinosideA);HA-16:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-25-acetoxy-9(11)-holostene-3β,12α-diol(pervicosideA);HA-17:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-holostene-3β-ol(axilogosideG);HA-18:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-xylopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-holostene-3β-ol(axilogosideB);HA-19:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α-diol(axilogosideC);HA-20:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11)-holostene-3β,12α-diol(axilogosideH).
From the ethanolic extracts of Thyone anomala, six compounds were isolated and identified, and the structures were identified as the below, TA-1: 3-O-[3-O-methyl -β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holostene-9(11)-ene-3β,12α,17α-triol(holothurinA);TA-2:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22-hydroxyholos t-9(11)-ene-holostene-3β,12α,17α-triol(holothurinA1);TA-3:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α-diol(anomalosideA);TA-4:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-holostene-3β,12α,17α-triol(echinosideA);TA-5:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α,17α-triol(holothurinB);TA-6:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-holostene-3β,12α,17α-triol(echinoside B).
From the ethanolic extracts of Actinopyga miliaris, sixteen compounds were isolated and identified, and the structures were identified as the below, AM-1:3-O-{(3-O-methyl-β- D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-9 (11),24(25)-holostene-3β,12α,22-triol(miliarisideA);AM-2:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α,17α-triol(miliarisideB);AM-3:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyra-nosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-24-oxo-9(11)-holostene-3β,12α-diol(miliarisideC);AM-4:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-16-acetoxy-9(11),24(25)-holostene-3β,12α,17α-triol(miliarisideD);AM-5:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyra-nosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-9(11)-holostene-3β,12α-diol(bivittosideD);AM-6:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α,17α-triol(holothurinA);AM-7:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-holostene-3β,12α,17α-triol(echinosideA);AM-8:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α,17α-triol(holothurinB);AM-9:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-3β,12α,17α-triol(echinosideB);AM-10:3-O-{(3-O-methyl-β-D-glucopyra nosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-9(11),24(25)-holostene-3β,12α-diol(miliarisideE);AM-11:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α-triol(miliarisideE);AM-12:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-25-acetoxy-9(11)-holostene-3β,12α-diol(miliariside F). And four sterols:AM-13:3β-sodiumsulfate-5α-cholesta-7(8),24-diene;AM-14:3β-sodiumsulfate-24-methyl-7(8)-ene-5α-cholesta;AM-15:3β-sodiumsulfate-7(8)-ene-5α-cholesta; AM-16: 3β- sodiumsulfate-5α-cholesta.
The preliminary cytotoxic assay of these saponins indicated that BEL-740, HL-60, A-549 and P388. In the anti-fungus screen, six triterpene glycosides were confirmed active against several fungus lines.
Our studies focused on bioactive constituents of Holothuria axiloga, Thyone anomala and Actinopyga miliaris have established a foundation for further research and development of the kind sea cucumber with abundant resources in South China Sea, and provided important leading compounds for the development of new anti-cancer and anti-fungus drugs.
从奇乳海参中分离鉴定了20个三萜皂苷化合物,其化学结构鉴定如下,HA-1: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃木糖基基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8),25(26)-海参烷烯-3β-醇(stichloroside A2);HA-2: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃木糖基基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8)-海参烷烯-3β-醇(stichloroside A1);HA-3: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃木糖基基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}- 23-乙酰氧基-7(8),25(26)-海参烷烯-3β-醇(stichloroside C2) ; HA-4: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃木糖基基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8)-海参烷烯-3β-醇(stichloroside C1);HA-5: 3-O-[β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸-β-D-吡喃木糖基]-22,25-环氧-9 (11)-海参烷烯-3β,12α,17α-三醇(axilogoside A);HA-6: 3-O-[β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin B);HA-7: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1?3)-β-D-吡喃葡萄糖-(1?4)-β-D-吡喃奎诺糖-(1?2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1?3)-β-D-吡喃葡萄糖-(1?4)]-β-D-吡喃木糖}-22,25-环氧-海参烷-9 (11)-烯-3β,12α,17α-三醇(marmoroside G);HA-8: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin A);HA-9:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-3β,12α-二醇(pervicoside C);HA-10: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22-羰基-9(11)-海参烷烯-3β,12α-二醇(fuscocineroside B);HA-11: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22-羰基-25-乙酰氧基-9 (11)-海参烷烯-3β,12α-二醇(fuscocineroside A);HA-12: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9 (11)-海参烷烯-3β,12α-二醇(fuscocineroside C) ; HA-13: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-9(11),24(25)-海参烷烯-3β,12α-二醇(axilogoside C);HA-14: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-22-羟基-3β,12α,17α-三醇(holothurin A1);HA-15: 3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-3β,12α,17α-三醇(echinoside A);HA-16: 3-O- [(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-25-乙酰氧基-9(11)-海参烷烯-3β,12α-二醇(pervicoside A);HA-17:3-O-{(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃葡萄糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)]-β-D-吡喃木糖基}-23-乙酰氧基-7(8)-海参烷烯-3β-醇(axilogoside G);HA-18:3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃木糖-(1→4)-β-D-吡喃木糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-海参烷-23-乙酰氧基-7 (8)-烯-3β-醇(axilogoside B);HA-19:3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃木糖-(1→4)-β-D-吡喃葡萄糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-海参烷-23-乙酰氧基-7 (8)-烯-3β-醇(axilogoside C);HA-20:3-O-{(3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-海参烷-23-乙酰氧基-9 (11)-烯-3β, 12α-二醇(axilogoside H)。
从异常赛瓜参中分离鉴定的6个海参皂苷为:TA-1:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin A);TA-2:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-22-羟基-3β,12α,17α-三醇(holothurin A1);TA-3:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-22,25-环氧-9(11)-海参烷-烯-3β,12α-二醇(anomaloside A);TA-4:3-O-[(3-O-甲基-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃葡萄糖基-(1→4)-β-D-吡喃奎诺糖基-(1→2)-4-O-硫酸钠-β-D-吡喃木糖基]-9(11)-海参烷烯-3β,12α,17α-三醇(echinoside A);TA-5:3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇( holothurin B);TA-6:3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-9(11)-海参烷-3β,12α,17α-三醇(echinoside B)。还得到2个甾体类化合物。
从乌皱辐肛参中分离鉴定的12个海参皂苷为:AM-1: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-9 (11), 24 (25)-海参烷烯-3β, 12α,22-三醇(miliariside A);AM-2: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-23-乙酰氧-9 (11), 24 (25)-海参烷烯-3β, 12α, 17α-三醇(miliariside B);AM-3: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)- [(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-24-羰基-9 (11)-海参烷烯-3β, 12α-二醇(miliariside C);AM-4: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-16-乙酰氧基-9 (11), 24 (25)-海参烷烯-3β, 12α, 17α-三醇(miliariside D);AM-5: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-9(11)-海参烷烯-3β, 12α-二醇(bivittoside D);AM-6: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-9(11)-海参烷烯-3β,12α,17α-三醇(holothurin A) ; AM-7: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-3β,12α,17α-三醇(echinoside A);AM-8: 3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(holothurin B);AM-9: 3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-9(11)-海参烷烯-3β,12α,17α-三醇(echinoside B);AM-10: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-9 (11), 24 (25)-海参烷烯-3β, 12α-三醇(impatenside A);AM-11: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-[β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-23-乙酰氧基-9 (11), 24 (25)-海参烷烯-3β, 12α-二醇(miliariside E);AM-12: 3-O-{(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖基-(1→2)-[(3-O-甲基-β-D-吡喃葡萄糖)-(1→3)-β-D-吡喃葡萄糖-(1→4)]-β-D-吡喃木糖}-25-乙酰氧基-9 (11)-海参烷烯-3β, 12α-二醇(miliariside F)。另外还得到4个甾体类化合物:AM-13: 3β-硫酸钠-5α-7(8),24-胆甾二烯, AM-14:3β-硫酸钠-24-乙基-5α-7(8)-胆甾烯,AM-15:3β-硫酸钠-5α-7(8)-胆甾烯, ,AM-16:3β-硫酸钠-5α-胆甾。
初步的药理活性筛选表明:海参皂苷对稻瘟霉显示显著的生物活性;从异常赛瓜参中分离得到的6个海参皂苷对BEL-7402人肝癌细胞、HL-60人白血病细胞、A-549人肺癌细胞和P388小鼠白血病细胞都具有细胞毒活性;所有分离得到的38个皂苷类化合物对白色念珠菌,新生隐球菌和红色毛癣菌等均具有不同强度的抑制生长作用。
本课题对三种海参的化学成分和生物活性进行的深入系统研究,为研发海洋来源的抗肿瘤和抗真菌药物提供了新的先导化合物,为开发海参的药用价值提供了科学依据,为海洋天然产物化学积累了新的研究资料,对开发我国丰富的海洋生物资源具有重要的意义。
Holothuria axiloga, Thyone anomala and Actinopyga miliaris distributed abundantly in South China Sea. Guided by Pyricularia oryzae bioassay model, the anti-cancer and anti-fungal constituents of Holothuria axiloga, Thyone anomala and Actinopyga miliaris have been investigated by various chromatography methods including LPLC, MPLC, HPLC on silica gel, ODS RP C18 and Zorbax SB C18 respectively. Forty-two compounds were isolated and structures of all the compounds were elucidated by chemical and spectral analysis (IR, EI-MS, ESI-MS, HRESI-MS, 1HNMR, 13CNMR, 1H-1H COSY, DQCOSY, TOCSY, HMQC, HMBC, NOESY, etc.).
From the ethanolic extracts of H. axiloga, twenty triterpene glycosides were isolated and the structures were identified as the below, HA-1:3-O-{(3-O-methyl-β-D-glucopyra nosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-xylopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8),25(26)-holostene-3β-ol(stichlorosideA2);HA-2:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-xylopyranosyl-(1→2)-[(3-O-methyl-β-D-glucop-yranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-hol-ostene-3β-ol(stichlorosideA1);HA-3:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8),25(26)-holo-stene-3β-ol(stichlorosideC2);HA-4:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-holostene-3β-ol(stichlorosideC1);HA-5:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sulfo-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(axilogosideA);HA-6:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(holothurinB);HA-7:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyran-osyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(marmorosideG);HA-8:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α,17α-triol(holothurinA);HA-9:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-9(11)-holostene-3β,12α-diol(pervicosideC);HA-10:3-O-[(3-O-methyl- β-D-glucopyranosyl)-(1→3)-β-D-glu-copyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22-one-9(11)-holostene-3β,12α-diol(fuscocinerosideB);HA-11:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22-one-25-acetoxy-9(11)-holostene-3β,12α-diol(fuscocinerosideA);HA-12:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3β,12α-diol(fuscocinerosideC);HA-13:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α-diol(axilogosideC);HA-14:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylop-yranosyl]-9(11)-holostene-3β,12α,17α,22-tetrol(holothurinA1);HA-15:3-O-[(3-O-me-thyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-9(11)-holostene-3β,12α,7α-triol(echinosideA);HA-16:3-O-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfato-β-D-xylopyranosyl]-25-acetoxy-9(11)-holostene-3β,12α-diol(pervicosideA);HA-17:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-holostene-3β-ol(axilogosideG);HA-18:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-xylopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-7(8)-holostene-3β-ol(axilogosideB);HA-19:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α-diol(axilogosideC);HA-20:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11)-holostene-3β,12α-diol(axilogosideH).
From the ethanolic extracts of Thyone anomala, six compounds were isolated and identified, and the structures were identified as the below, TA-1: 3-O-[3-O-methyl -β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holostene-9(11)-ene-3β,12α,17α-triol(holothurinA);TA-2:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22-hydroxyholos t-9(11)-ene-holostene-3β,12α,17α-triol(holothurinA1);TA-3:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α-diol(anomalosideA);TA-4:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-holostene-3β,12α,17α-triol(echinosideA);TA-5:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α,17α-triol(holothurinB);TA-6:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-holostene-3β,12α,17α-triol(echinoside B).
From the ethanolic extracts of Actinopyga miliaris, sixteen compounds were isolated and identified, and the structures were identified as the below, AM-1:3-O-{(3-O-methyl-β- D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-9 (11),24(25)-holostene-3β,12α,22-triol(miliarisideA);AM-2:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α,17α-triol(miliarisideB);AM-3:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyra-nosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-24-oxo-9(11)-holostene-3β,12α-diol(miliarisideC);AM-4:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-16-acetoxy-9(11),24(25)-holostene-3β,12α,17α-triol(miliarisideD);AM-5:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyra-nosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-9(11)-holostene-3β,12α-diol(bivittosideD);AM-6:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α,17α-triol(holothurinA);AM-7:3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-holostene-3β,12α,17α-triol(echinosideA);AM-8:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-9(11)-ene-holostene-3β,12α,17α-triol(holothurinB);AM-9:3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-9(11)-ene-3β,12α,17α-triol(echinosideB);AM-10:3-O-{(3-O-methyl-β-D-glucopyra nosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-9(11),24(25)-holostene-3β,12α-diol(miliarisideE);AM-11:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-23-acetoxy-9(11),24(25)-holostene-3β,12α-triol(miliarisideE);AM-12:3-O-{(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-[(3-O-methyl-β-D-glucopyranosyl)-(1→3)-β-D-glucopyranosyl-(1→4)]-β-D-xylopyranosyl}-25-acetoxy-9(11)-holostene-3β,12α-diol(miliariside F). And four sterols:AM-13:3β-sodiumsulfate-5α-cholesta-7(8),24-diene;AM-14:3β-sodiumsulfate-24-methyl-7(8)-ene-5α-cholesta;AM-15:3β-sodiumsulfate-7(8)-ene-5α-cholesta; AM-16: 3β- sodiumsulfate-5α-cholesta.
The preliminary cytotoxic assay of these saponins indicated that BEL-740, HL-60, A-549 and P388. In the anti-fungus screen, six triterpene glycosides were confirmed active against several fungus lines.
Our studies focused on bioactive constituents of Holothuria axiloga, Thyone anomala and Actinopyga miliaris have established a foundation for further research and development of the kind sea cucumber with abundant resources in South China Sea, and provided important leading compounds for the development of new anti-cancer and anti-fungus drugs.
引文
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