南海软珊瑚共附生真菌Aspergillus sp.EGF15-0-3苯甲醛类化合物研究

Research on benzaldehydes from the soft coral-associated symbiotic fungus Aspergillus sp.EGF15-0-3

本文研究了具有克服肿瘤耐药活性的软珊瑚共附生真菌Aspergillus sp.EGF 15-0-3苯甲醛类化学成分。采用硅胶柱层析、十八烷基硅烷键合硅胶层析、Sephadex LH-20层析、高效液相色谱(high performance liquid chromatography,HPLC)等多种方法进行分离纯化;通过核磁共振波谱(nuclear magnetic resonance,NMR)、质谱(mass spectrometry,MS)等现代波谱分析及物理常数对照等方法进行结构鉴定;采用MTT法对苯甲醛部位和单体化合物进行克服肿瘤耐药活性研究。从EGF15-0-3的苯甲醛部位共得到9个苯甲醛类化合物,结构依次为flavoglaucin(1)、tetrahydroauroglaucin(2)、isoaspergin(3)、isotetrahydroauro-glaucin(4)、dihydroauroglaucin(5)、isodihydroauroglaucin(6)、2-(1',5'-heptadienyl)-3,6-dihydroxy-5-(3''-methyl-2''-butenyl)benzaldehyde(7)、auro-glaucin(8)和2-(2',3-epoxy-1'-heptenyl)-6-hydroxy-5-(3''methyl-2''-butenyl)benzaldehyde(9)。体外克服肿瘤耐药活性研究表明,苯甲醛类化合物9具有较强的克服肿瘤耐药活性,可能是由于其结构2位烷基侧链与3羟基形成吡喃环所致。

To research the benzaldehydes of the soft coral-associated symbiotic fungus Aspergillus sp.EGF 15-0-3 with the activity of overcoming tumor resistance,the secondary metabolites were isolated by silica gel column chromatography,ODS,Sephadex LH-20,thin layer chromatography,and high performance liquid chromatography(HPLC).The structures of compounds were identified by nuclear magnetic resonance(NMR),mass spectrometry(MS),and literature analysis.Nine benzaldehydes were obtained and elucidated as follows:flavoglaucin(1),tetrahydroauroglaucin(2),isoaspergin(3),isotetrahydroauroglaucin(4),dihydroauroglaucin(5),isodihydroauroglaucin(6),2-(1',5'-heptadienyl)-3,6-dihydroxy-5-(3''-methyl-2''-butenyl)benzaldehyde(7),auro-glaucin(8),and 2-(2',3-epoxy-1'-heptenyl)-6-hydroxy-5-(3''methyl-2''-butenyl)benzal-dehyde(9).Using the MTT[3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide]method,compound 9 showed strong activity to drug-resistant tumor cell lines H1975/GR.This may be due to the structure of a pyran ring between the 2-position side chain and 3-hydroxyl group.