来源于南海红树林底泥抗菌放线菌的活性化学成分研究
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摘要
本论文对两株来源于我国南海红树林底泥且具有抗菌活性的海洋放线菌(No.H74-18和No.H41-26)的发酵液和菌丝体进行了活性成分的分离和结构鉴定。利用硅胶开放柱色谱、ODS开放柱色谱、制备性HPLC和葡聚糖LH-20排阻层析等多种色谱方法,从活性流分中分离得到得到21个单体样品、1个结晶和1个混晶,经MS、1D及2D-NMR或X-衍射等谱学方法鉴定了其中12个化合物结构。它们分别为抗霉素类化合物：抗霉素A1a(1)、抗霉素A1b(2)、抗霉素A2a(3)、抗霉素A3a(4)、抗霉素A3b(5)、(2S,3R,6R,8S)-3-(3-formamido-2-hydroxybenzamido)-8-hexyl-2,6-dimethyl-4,9-dioxo-1,5-diox onan-7-yl acetate(抗霉素A18,6)、(2S,3R,6R,8S)-3-(3-formamido-2-hydroxybenzamido)-2,6-dimethyl-4,9-dioxo-8-pentyl-1,5-dioxonan-7-yl-2,3-dimethylbutanoatei(抗霉素A19,7)；放线菌素类化合物：放线菌素D(8)、放线菌素X2(9)、actinomycin放线菌素X0β(10)、放线菌素X0δ(11)；其他类型化合物：吡虫啉(1)。其中化合物6、7为新天然产物。
This thesis has studied on the isolation and structural determination of active constituents in fermented mycelium and broth from two strains of marine actinomycetes No. H74-18 and No. H41-26, which were isolated from the bottom soil of mangrove zone in south China sea and showed antibiotic activity. Twenty-one pure samples, one crystal sample and one mixed crystal sample were isolated from the active fractions by silica gel column, ODS open column chromatography, preparative HPLC, Sephadex LH-20 permeation chromatography, and other chromatographic techniques. Twelve compounds were identified by MS, 1D and 2D NMR spectroscopic analysis, or X-ray diffraction analysis, they were determined to be 7 antimycins as antimycin A1a(1), antimycin A1b(2), antimycin A2a(3), antimycin A3a(4), antimycin A3b(5), (2S,3R,6R,8S)-3-(3-formamido-2-hydroxybenzamido)-8-hexyl-2,6-dimethyl-4,9-dioxo-1,5-diox onan-7-yl acetate (antimycin A1g,6),
(2S,3R,6R,8S)-3-(3-formamido-2-hydroxybenzamido)-2,6-dimethyl-4,9-dioxo-8-pentyl-1,5-dio xonan-7-yl 2,3-dimethylbutanoate (antimycin A19,7).4 actinomycins as actinomycin D (8), actinomycin X2 (9), actinomycin X0p (10), actinomycin X0s(11), and imidacloprid (12). Compounds 6 and 7 were two new natural products..
This thesis has studied on the isolation and structural determination of active constituents in fermented mycelium and broth from two strains of marine actinomycetes No. H74-18 and No. H41-26, which were isolated from the bottom soil of mangrove zone in south China sea and showed antibiotic activity. Twenty-one pure samples, one crystal sample and one mixed crystal sample were isolated from the active fractions by silica gel column, ODS open column chromatography, preparative HPLC, Sephadex LH-20 permeation chromatography, and other chromatographic techniques. Twelve compounds were identified by MS, 1D and 2D NMR spectroscopic analysis, or X-ray diffraction analysis, they were determined to be 7 antimycins as antimycin A1a(1), antimycin A1b(2), antimycin A2a(3), antimycin A3a(4), antimycin A3b(5), (2S,3R,6R,8S)-3-(3-formamido-2-hydroxybenzamido)-8-hexyl-2,6-dimethyl-4,9-dioxo-1,5-diox onan-7-yl acetate (antimycin A1g,6),
(2S,3R,6R,8S)-3-(3-formamido-2-hydroxybenzamido)-2,6-dimethyl-4,9-dioxo-8-pentyl-1,5-dio xonan-7-yl 2,3-dimethylbutanoate (antimycin A19,7).4 actinomycins as actinomycin D (8), actinomycin X2 (9), actinomycin X0p (10), actinomycin X0s(11), and imidacloprid (12). Compounds 6 and 7 were two new natural products..
引文
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[10]Charan R.D., Schlingmann G., Janso J. Diazepinomicin, a new antimicrobial alkaloid from Micromonospora sp[J]. J. Nat. Prod.,2004,67(8):1431-1433.
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[12]Hotta K., Yoshida M., Hamada M. Studies on new aminoglycoside antibiotics, istamycins, from an actinomycete isolated from a marine environment. Ⅲ. Nutritional effects on istamycin production and additional chemical and biological properties of istamycins[J]. J. Antibiot.,1980, 33(12):1515-1520.
[13]王淑霞,朱天骄,卢圳域.海洋新放线菌及其次级代谢产物研究进展[J].中国抗生素杂志,2007,9(32)：513～519.
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[15]Renner M.K., S.Y.-C, Cheng X.C. Cyclomarins A-C, new aniiinflammatory cyclic peptides produced by a marine bacterium (Streptomyces sp.)[J].J.Am. Chem. Soc.,1999, 121(49):11273-11276.
[16]温学义.抗生素作用机理研究进展[J].吉林医学,1982,3(3)：51-53.
[17]余国文,汤小胜.抗菌剂作用机理的探讨[J].黄石理工学院院报,2008,24(6)：29-32.
[18]顾觉奋.抗生素[M].上海：科学技术出版社,2001：1-20
[19]吕玲玲,雷建军,宋明.抗生素的研究及其在农业上的应用[J].微生物学杂志,2003,23(1)40-45.
[20]Yamaguchi H.微生物来源农药的研究进展[J].国外医药(抗生素)分册,1990,11(2)：137-141.
[21]Lardy H.A., Ferguson S.M. Oxidative phosphorylation in mitochondria[J]. Ann. Rev. Biochem.,1969,38:991-1034.
[22]马悦欣,王岩,刘璐.大连海区潮间带海藻附生细菌的抗微生物活性[J].大连水产学院学报,2003,18(4)：252-257.
[23]骆祝华,黄翔玲,刘文华.海洋微生物抗菌活性的初步研究[J].中国海洋药物,2005,24(2)：26-31.
[24]谢海平,黄晖,黄登峰.海洋枯草芽孢杆菌Bs-1产生多种抗真菌活性物质[J].中山大学学报(自然科学版),2003,42(3)：122-123.
[25]李淑彬,陆广欣,林如妹.具抗真菌活性的海洋霉菌的筛选和初步研究[J].微生物学通报,2005,32(2)：76-82.
[26]姜健,杨宝灵.海洋微生物生物活性物质的研究[J].云南大学学报,2004,26(6A)：91-95.
[27]王艳艳,刘常宏,陈欣.海岸盐沼湿地细菌抗真菌活性研究[J].中国农学通报,2006,22(12)：56-58.
[28]廖文彬,鲍时翔.红树林放线菌产抗菌活性物质的分离纯化研究[J].药物生物技术,2004.6：376-378.
[29]Barrow C., Oleynek J., Marinelli V. Antimycins, inhibitord of ATP-citrate lyase, from a Steptomyces sp.[J]. J. Antibiot,1997,50(9):729-733.
[30]付海抄,赵文英,钟惠民.海绵来源放线菌sh6004发酵产物中的活性生物碱[J].中国海洋药物杂志,2008,27(4)：14-20
[31]Nicole S., Wolfgang S. Synthesis of the 15N-labelled insecticide imidacloprid[J]. J. Label Compd Radiopharm.,2006,49:305-310.
[32]John S.R., Lipton S.H., Harold B. Factor affecting the binding of Antimycin A to complex III of the mitochondrial respiratory chain[J]. J.Biol. Chem,1967,242(21):4888-4896.
[2]王波云,李立安,顾亚夫.细菌耐药性研究进展与对策[J].解放军药学学报,2001,17(5)：259-261.
[3]陈代杰.微生物药物学[M].上海：华东理工大学出版社,1999：37-52.
[4]Kelecom A. Secondary metabolites from marine microorganisms[J]. Ann. Braz. Acad. Sci., 2002,74(1):151-170.
[5]詹萍,梁静娟,庞宗文.产生活性物质海洋微生物的研究进展[J].玉林师范学院学报(自然科学),2007,28(3)：71-74.
[6]张清丽,顾谦群,崔承彬.海洋来源的放线菌次级代谢产物及其生物活性[J].中国海洋药物杂志,2004,23(5)：49-54.
[7]刘妍,李志勇.海洋放线菌研究的新进展[J].生物技术通报,2005,(6)：34-39.
[8]Pathirana C., Jensen P.R., Fenical W. Marinone and deboromarinone:antibiotic sesquiterpenoid naphthoquinones of a new structure class from a marine bacterium[J]. Tetrahedron. Lett.,1992,33(50):7663-7666.
[9]Cheng X.C., Jensen P.R, Fenical W. Luisols A and B, new aromatic tetraols produced by an Estuarine marine bacterium of the genus Streptomyces (Actinomycetales)[J]. J. Nat. Prod.,1999, 62(4):608-601.
[10]Charan R.D., Schlingmann G., Janso J. Diazepinomicin, a new antimicrobial alkaloid from Micromonospora sp[J]. J. Nat. Prod.,2004,67(8):1431-1433.
[11]Capon R.J., Skene C., Lacey E. Lorneamides A and B:two new aromatic amides from a southern Australian marine actinomycete[J]. J. Nat. Prod.,2000,63(12):1682-1683.
[12]Hotta K., Yoshida M., Hamada M. Studies on new aminoglycoside antibiotics, istamycins, from an actinomycete isolated from a marine environment. Ⅲ. Nutritional effects on istamycin production and additional chemical and biological properties of istamycins[J]. J. Antibiot.,1980, 33(12):1515-1520.
[13]王淑霞,朱天骄,卢圳域.海洋新放线菌及其次级代谢产物研究进展[J].中国抗生素杂志,2007,9(32)：513～519.
[14]Imamura N., Nishijima M., Adachi K. Novel antimycin antibiotics urauchimycins A and B, produced by marine actinomycete[J]. J. Antibiot.,1993,46(2):241-246.
[15]Renner M.K., S.Y.-C, Cheng X.C. Cyclomarins A-C, new aniiinflammatory cyclic peptides produced by a marine bacterium (Streptomyces sp.)[J].J.Am. Chem. Soc.,1999, 121(49):11273-11276.
[16]温学义.抗生素作用机理研究进展[J].吉林医学,1982,3(3)：51-53.
[17]余国文,汤小胜.抗菌剂作用机理的探讨[J].黄石理工学院院报,2008,24(6)：29-32.
[18]顾觉奋.抗生素[M].上海：科学技术出版社,2001：1-20
[19]吕玲玲,雷建军,宋明.抗生素的研究及其在农业上的应用[J].微生物学杂志,2003,23(1)40-45.
[20]Yamaguchi H.微生物来源农药的研究进展[J].国外医药(抗生素)分册,1990,11(2)：137-141.
[21]Lardy H.A., Ferguson S.M. Oxidative phosphorylation in mitochondria[J]. Ann. Rev. Biochem.,1969,38:991-1034.
[22]马悦欣,王岩,刘璐.大连海区潮间带海藻附生细菌的抗微生物活性[J].大连水产学院学报,2003,18(4)：252-257.
[23]骆祝华,黄翔玲,刘文华.海洋微生物抗菌活性的初步研究[J].中国海洋药物,2005,24(2)：26-31.
[24]谢海平,黄晖,黄登峰.海洋枯草芽孢杆菌Bs-1产生多种抗真菌活性物质[J].中山大学学报(自然科学版),2003,42(3)：122-123.
[25]李淑彬,陆广欣,林如妹.具抗真菌活性的海洋霉菌的筛选和初步研究[J].微生物学通报,2005,32(2)：76-82.
[26]姜健,杨宝灵.海洋微生物生物活性物质的研究[J].云南大学学报,2004,26(6A)：91-95.
[27]王艳艳,刘常宏,陈欣.海岸盐沼湿地细菌抗真菌活性研究[J].中国农学通报,2006,22(12)：56-58.
[28]廖文彬,鲍时翔.红树林放线菌产抗菌活性物质的分离纯化研究[J].药物生物技术,2004.6：376-378.
[29]Barrow C., Oleynek J., Marinelli V. Antimycins, inhibitord of ATP-citrate lyase, from a Steptomyces sp.[J]. J. Antibiot,1997,50(9):729-733.
[30]付海抄,赵文英,钟惠民.海绵来源放线菌sh6004发酵产物中的活性生物碱[J].中国海洋药物杂志,2008,27(4)：14-20
[31]Nicole S., Wolfgang S. Synthesis of the 15N-labelled insecticide imidacloprid[J]. J. Label Compd Radiopharm.,2006,49:305-310.
[32]John S.R., Lipton S.H., Harold B. Factor affecting the binding of Antimycin A to complex III of the mitochondrial respiratory chain[J]. J.Biol. Chem,1967,242(21):4888-4896.
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