棕环海参和紫伪翼手参生物活性成分的研究
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摘要
本文介绍了我国南海两种海参——棕环海参(Holothuria fuscocinerea Jaegar)和紫伪翼手参(Pseudocolochirus violaceus Theel)中生物活性成分的研究。本研究以稻瘟霉模型作为活性监测手段,应用正相硅胶、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,对两种海参所含的抗肿瘤和抗真菌活性成分进行了系统的分离纯化和药理研究。共分离得到单体化合物24个(棕环海参11个,紫伪翼手参13个),应用现代波谱技术和化学手段鉴定了其中21个化合物的结构,均为首次从上述海参中获得,其中新化合物8个。
从棕环海参中分离鉴定了10个化合物,包括6个海参皂苷和4个其它化合物。6个海参皂苷的化学结构为: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-二醇(HF-1,pervicoside C),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]-25-乙酰氧基-海参烷-9(11)-烯-22-酮-3β,12α-二醇(HF-2,fuscocineroside A),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-22-酮-3β,12α-二醇(HF-3,fuscocineroside B),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-海参烷-9(11)-烯-3β,12α-二醇(HF-4,fuscocineroside C),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-海参烷-9(11)-烯-3β,12α,17α-三醇(HF-5,holothurin A)和3-O-[β-D-吡喃奎诺糖-(1→2)-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HF-6,DS-holoturin B);4个其它化合物为:尿嘧啶(HF-7),胸腺嘧啶(HF-8),胸腺嘧啶脱氧核苷(HF-10)和尿嘧啶脱氧核苷(HF-11)。
从紫伪翼手参中分离鉴定了1 1个化合物,包括7个海参皂苷和4个甾醇苷。7个海参皂苷的化学结构为: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-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-16β-乙酰氧基-海参烷-7,24-二烯-3β-醇(PV-1,philinopside A),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)-4-O-硫酸钠-β-D-吡喃木糖]-16β-乙酰氧基-海参烷-7,24-二烯-3β-醇(PV-2,violaceside A),3-O-[3-O-甲基-β-D-吡喃
Holothuria fuscocinerea and Pseudocolochirus violaceus are abundant sea cucumbers distributed in South China Sea. No chemical works have been performed on these sea cucumbers up to date. Guided by Pyricularia oryzae bioassay model, the anticancer and antifungal constituents of H. fuscocinerea and P. violaceus have been investigated by various chromatography methods including LPLC, MPLC, HPLC on silica gel, ODS RP C_(18) and Zorbax SB C_(18) respectively. Twenty-four compounds were isolated and chemical structures of twenty-one were elucidated by chemical and spectral analysis (IR, EI-MS, ESI-MS, HRESI-MS, ~1H NMR, ~(13)C NMR, ~1H-~1H COSY, DQCOSY, TOCSY, HMQC, HMBC, NOESY, etc).From the ethanolic extracts of H. fuscocinerea, ten compounds were isolated and identified, including six triterpene glycosides: 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3) -β-O-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylo-pyranosyl]-holosta-9(11)-ene-3β, 12α-diol (HF-1, pervicoside C), 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]-25-acetoxy-holosta-9(11)-ene-22-one-3β, 12α-diol (HF-2), 3-O- [3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovo-pyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-holosta-9(11)-ene-22-one-3β, 12α -diol (HF-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-holosta-9(11)-ene-3β, 12α-diol (HF-4), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-gluco-pyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β, 12α, 17α-triol (HF-5, holothurin A) and 3-O-[β-D-quinovopyranosyl-(1→2)-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α, 17α-triol (HF-6, DS-holothurin B); and four other type compounds: uracil (HF-7), thymine (HF-8), thymidine (HF-10) and 2'-deoxyuridine (HF-11).From the ethanolic extracts of P. violaceus, the chemical structures of eleven compounds were elucidated, including seven triterpene glycosides: 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-(1→2)-quinovopyranosyl-4-O-sodiumsulfate-β-D-xylopyranosyl]-16p-acetoxy-holosta-7, 24-diene-3β-ol (PV-1, philinop-side A), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-glucopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-16β-acetoxy-holosta-7, 24-diene-3β-ol (PV-2), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-xylopyranosyl-(1→
从棕环海参中分离鉴定了10个化合物,包括6个海参皂苷和4个其它化合物。6个海参皂苷的化学结构为: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-二醇(HF-1,pervicoside C),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]-25-乙酰氧基-海参烷-9(11)-烯-22-酮-3β,12α-二醇(HF-2,fuscocineroside A),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-22-酮-3β,12α-二醇(HF-3,fuscocineroside B),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-海参烷-9(11)-烯-3β,12α-二醇(HF-4,fuscocineroside C),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-海参烷-9(11)-烯-3β,12α,17α-三醇(HF-5,holothurin A)和3-O-[β-D-吡喃奎诺糖-(1→2)-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HF-6,DS-holoturin B);4个其它化合物为:尿嘧啶(HF-7),胸腺嘧啶(HF-8),胸腺嘧啶脱氧核苷(HF-10)和尿嘧啶脱氧核苷(HF-11)。
从紫伪翼手参中分离鉴定了1 1个化合物,包括7个海参皂苷和4个甾醇苷。7个海参皂苷的化学结构为: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-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-16β-乙酰氧基-海参烷-7,24-二烯-3β-醇(PV-1,philinopside A),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)-4-O-硫酸钠-β-D-吡喃木糖]-16β-乙酰氧基-海参烷-7,24-二烯-3β-醇(PV-2,violaceside A),3-O-[3-O-甲基-β-D-吡喃
Holothuria fuscocinerea and Pseudocolochirus violaceus are abundant sea cucumbers distributed in South China Sea. No chemical works have been performed on these sea cucumbers up to date. Guided by Pyricularia oryzae bioassay model, the anticancer and antifungal constituents of H. fuscocinerea and P. violaceus have been investigated by various chromatography methods including LPLC, MPLC, HPLC on silica gel, ODS RP C_(18) and Zorbax SB C_(18) respectively. Twenty-four compounds were isolated and chemical structures of twenty-one were elucidated by chemical and spectral analysis (IR, EI-MS, ESI-MS, HRESI-MS, ~1H NMR, ~(13)C NMR, ~1H-~1H COSY, DQCOSY, TOCSY, HMQC, HMBC, NOESY, etc).From the ethanolic extracts of H. fuscocinerea, ten compounds were isolated and identified, including six triterpene glycosides: 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3) -β-O-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylo-pyranosyl]-holosta-9(11)-ene-3β, 12α-diol (HF-1, pervicoside C), 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]-25-acetoxy-holosta-9(11)-ene-22-one-3β, 12α-diol (HF-2), 3-O- [3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovo-pyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-holosta-9(11)-ene-22-one-3β, 12α -diol (HF-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-holosta-9(11)-ene-3β, 12α-diol (HF-4), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-gluco-pyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β, 12α, 17α-triol (HF-5, holothurin A) and 3-O-[β-D-quinovopyranosyl-(1→2)-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α, 17α-triol (HF-6, DS-holothurin B); and four other type compounds: uracil (HF-7), thymine (HF-8), thymidine (HF-10) and 2'-deoxyuridine (HF-11).From the ethanolic extracts of P. violaceus, the chemical structures of eleven compounds were elucidated, including seven triterpene glycosides: 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-(1→2)-quinovopyranosyl-4-O-sodiumsulfate-β-D-xylopyranosyl]-16p-acetoxy-holosta-7, 24-diene-3β-ol (PV-1, philinop-side A), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)-β-D-glucopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-16β-acetoxy-holosta-7, 24-diene-3β-ol (PV-2), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-xylopyranosyl-(1→
引文
[1] Wallace RW. Drugs from the sea: harvesting the results of aeon chemical evolution[J]. Mol Med Today, 1997, 3(7): 291-295.
[2] 王洛伟,韩燕.海洋药物开发现状及展望[J].中华航海医学杂志,1991,(1):23-27.
[3] 廖玉麟,编著.中国动物志,棘皮动物门,海参纲[M].北京:科学出版社,1997:108-110.
[4] 樊绘曾.海参:海中人参[J].中国海洋药物,2001,20(4):37-44.
[5] Kobayashi H, Namikoshi M, Yoshimoto T, et al. A screening method for antimitotic and antifungal substance using conidia of Pyricularia oryzae, modification and application to tropical marine fungi[J]. J Antibiotics, 1996, 49(9): 873-879.
[6] Kitagawa I, Kobayashi M, Hori M, et al. Marine natural products. ⅩⅧ. Four lanostane-type triterpene oligoglycosides, bivittosides A, B, C and D, from the Okinawan sea cucumber Bohadschia bivittata Mitsukuri[J]. Chem Pharm Bull, 1989, 37(1): 61-67.
[7] 于德泉,杨峻山,主编.分析化学手册(第二版),第七分册:核磁共振波谱解析[M].北京:化学工业出版社,1999:495.
[8] Kitagawa I, kobayashi M, Son BW, et al. Marine natural products. ⅩⅨ. Pervicosides A, B, and C, lanostane-type triterpene-oligoglycoside sulfates from the sea cucumber Holothuria pervicax[J]. Chem Pharm Bull, 1989, 37(5): 1230-1234.
[9] De Marino S, Iorizzi M, Zollo F, et al. Starfish saponins, LⅥ. Three new asterosaponins from the starfish Goniopecten demonstrans[J]. Eur J Org Chem, 2000: 4093-4098.
[10] Rodriguez J, Castro R, Riguera R. Holothurinosides: new antitumour non sulphated triterpenoid glycosides from the sea cucumber Holothuria forskalii [J]. Tetrahedron, 1991, 47(26): 4753-4762.
[11] Kitagawa I, Nishino T, Kobayashi M, et al. Marine natural products. Ⅷ. Bioactive triterpene-oligoglycosides from the sea cucumber Holothuria leucospilota Brandt (2). Structure of holothurin A[J]. Chem Pharm Bull, 1981, 29(7): 1951-1956.
[12] Paul DE, Dunlap RB, Polliard AAAL, et al. Carbon-13 nuclear magnetic resonance of 5-substituted uracils[J]. J Am Chem Soc, 1973, 95(13): 4398.
[13] 邓松之,李凤英,谈燮峰,等.南海柳珊瑚 Isis sp.化学成分的研究[J].天然产物研究与开发,1994,6(4):9.
[14] Goldstein JH, Tarpey AR. Carbon-13 NMR spectra of uracil, thymine and the 5-halouracils[J]. J Am Chem Soc, 1973, 93(15):3573.
[15] 孟艳辉,苏镜娱,曾陇梅.南海软肉芝软珊瑚的化学成分研究[J].中国海洋药物,1999,18(3):1.
[16] Alan JJ, Winkely MW, Grant DM, et al. Carbon-13: naturally occurring nucleosides[J]. Proc Natl Acad Sci USA, 1970, 65(1): 27.
[17] Ericson LE, Widoff E, Bauhidi ZG. Studies of growth factors for streptococcus facalis occuring in marine algae[J]. Acta Chem Scand, 1953: 794.
[18] 劳彦斌,蒋亭,李军,等.柄海鞘Styela clava次生代谢产物的化学研究(Ⅰ)[J].中国海洋药物,2001,20(2):14.
[19] 彭学东,邓松之,肖定军,等.南海海绵Pseudoceratina purpurea活性成分研究Ⅱ[J].中国海洋药物,2004,23(1):11-13.
[20] Miyamoto, T, Togawa K, Higuchi R, et al. Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber Cucumaria echinata [J]. Liebigs Ann Chem, 1990: 453-460.
[21] Maier MS, Roccatagliata AJ, Kuriss A, et al. Two new cytotoxic and virucidal trisulfated triterpene glycosides from the Antarctic sea cucumber Staurocucumis liouvillei[J]. J Nat Prod, 2001, 64(6): 732-736.
[22] Chulidl HD, Muniain CC, Seldes AM, et al. Cytotoxic and antifungal triterpene glycosides from the Patagonian sea cucumber Hemoiedma spectabilis[J]. J Nat Prod, 2002, 65(6): 860-865.
[23] Drozdova OA, Avilov SA, Kalinin Ⅵ, et al. Cytotoxic triterpene glycosides from Far-Eastern sea cucumber belonging to the genus Cucumaria[J]. Liebigs Ann
[2] 王洛伟,韩燕.海洋药物开发现状及展望[J].中华航海医学杂志,1991,(1):23-27.
[3] 廖玉麟,编著.中国动物志,棘皮动物门,海参纲[M].北京:科学出版社,1997:108-110.
[4] 樊绘曾.海参:海中人参[J].中国海洋药物,2001,20(4):37-44.
[5] Kobayashi H, Namikoshi M, Yoshimoto T, et al. A screening method for antimitotic and antifungal substance using conidia of Pyricularia oryzae, modification and application to tropical marine fungi[J]. J Antibiotics, 1996, 49(9): 873-879.
[6] Kitagawa I, Kobayashi M, Hori M, et al. Marine natural products. ⅩⅧ. Four lanostane-type triterpene oligoglycosides, bivittosides A, B, C and D, from the Okinawan sea cucumber Bohadschia bivittata Mitsukuri[J]. Chem Pharm Bull, 1989, 37(1): 61-67.
[7] 于德泉,杨峻山,主编.分析化学手册(第二版),第七分册:核磁共振波谱解析[M].北京:化学工业出版社,1999:495.
[8] Kitagawa I, kobayashi M, Son BW, et al. Marine natural products. ⅩⅨ. Pervicosides A, B, and C, lanostane-type triterpene-oligoglycoside sulfates from the sea cucumber Holothuria pervicax[J]. Chem Pharm Bull, 1989, 37(5): 1230-1234.
[9] De Marino S, Iorizzi M, Zollo F, et al. Starfish saponins, LⅥ. Three new asterosaponins from the starfish Goniopecten demonstrans[J]. Eur J Org Chem, 2000: 4093-4098.
[10] Rodriguez J, Castro R, Riguera R. Holothurinosides: new antitumour non sulphated triterpenoid glycosides from the sea cucumber Holothuria forskalii [J]. Tetrahedron, 1991, 47(26): 4753-4762.
[11] Kitagawa I, Nishino T, Kobayashi M, et al. Marine natural products. Ⅷ. Bioactive triterpene-oligoglycosides from the sea cucumber Holothuria leucospilota Brandt (2). Structure of holothurin A[J]. Chem Pharm Bull, 1981, 29(7): 1951-1956.
[12] Paul DE, Dunlap RB, Polliard AAAL, et al. Carbon-13 nuclear magnetic resonance of 5-substituted uracils[J]. J Am Chem Soc, 1973, 95(13): 4398.
[13] 邓松之,李凤英,谈燮峰,等.南海柳珊瑚 Isis sp.化学成分的研究[J].天然产物研究与开发,1994,6(4):9.
[14] Goldstein JH, Tarpey AR. Carbon-13 NMR spectra of uracil, thymine and the 5-halouracils[J]. J Am Chem Soc, 1973, 93(15):3573.
[15] 孟艳辉,苏镜娱,曾陇梅.南海软肉芝软珊瑚的化学成分研究[J].中国海洋药物,1999,18(3):1.
[16] Alan JJ, Winkely MW, Grant DM, et al. Carbon-13: naturally occurring nucleosides[J]. Proc Natl Acad Sci USA, 1970, 65(1): 27.
[17] Ericson LE, Widoff E, Bauhidi ZG. Studies of growth factors for streptococcus facalis occuring in marine algae[J]. Acta Chem Scand, 1953: 794.
[18] 劳彦斌,蒋亭,李军,等.柄海鞘Styela clava次生代谢产物的化学研究(Ⅰ)[J].中国海洋药物,2001,20(2):14.
[19] 彭学东,邓松之,肖定军,等.南海海绵Pseudoceratina purpurea活性成分研究Ⅱ[J].中国海洋药物,2004,23(1):11-13.
[20] Miyamoto, T, Togawa K, Higuchi R, et al. Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber Cucumaria echinata [J]. Liebigs Ann Chem, 1990: 453-460.
[21] Maier MS, Roccatagliata AJ, Kuriss A, et al. Two new cytotoxic and virucidal trisulfated triterpene glycosides from the Antarctic sea cucumber Staurocucumis liouvillei[J]. J Nat Prod, 2001, 64(6): 732-736.
[22] Chulidl HD, Muniain CC, Seldes AM, et al. Cytotoxic and antifungal triterpene glycosides from the Patagonian sea cucumber Hemoiedma spectabilis[J]. J Nat Prod, 2002, 65(6): 860-865.
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