Studies On The Chemical Diversity Of Secondary Metabolites From Aspergillus Glaucus HB1-19

Chemical diversity and the novel biological activity of metabolites from marine fungi made a prominent contribution to the lead discovery of compounds. A study which was directed by OSMAC (One Strain Many Compounds), on manipulating the culture conditions of fungi Aspergillus glaucus HB1-19 was carried out to explore chemical diversity and search for new metabolites. Studies included: By changing cultural conditions, the silent biosynthetic pathway of the Aspergiolides (A-D) producing strain Aspergillus glaucus HB1-19 might be activated and produced more active Aspergiolide analogs. The isolated compounds were evaluated for their growth inhibition against PP-1c and bacterial.Our previous work had reported the isolation of Aspergiolides (A-D) from the marine-derived fungus Aspergillus glaucus HB1-19. These new skeleton Aspergiolides showed obviously cytotoxicity, PTK inhibition activity and TopⅡinhibition activity and Aspergiolide A have been developed as leading compound for antitumor drug. By manipulating culture conditions, using the fermentation tank to take the place of shake flask, the differences of HPLC finger printing of metabolites is significant.In order to research for active compounds, the EtOAC extract of the bioactive strain Aspergillus glaucus HB1-19 was chromatographed by repeated silica gel column, preparative TLC, Sephadex LH20, and semi-preparative HPLC, which lead to the isolation of 41compounds.Six new compounds, including benzaidehyde derivatives (1-2), one butyrolactone (3), quinones (4-5), butyrolactone compounds (6) were determined based on the physico-chemical properties, spectral data (IR, UV, MS, etc.) and NMR data, togethe with 24 known compounds, identified as seven benzaidehyde derivatives (7-13), seven polyketones (18,20-24,29), one steroid (19), four diketopiperazine alkaloids (include indole diketopiperazine and cyclic peptides) (14-17), four benzo-pyrone derivative (25-28), one benzol derivative (30). The identify of the rest compounds are still keep going.Summarily, 41 compounds were obtained from the EtOAc extracts of the bioactive strain Aspergillus glaucus HB1-19, and the structures of 28 compounds were identified, including 6 new compounds. The studies provided new structures for natural product chemistry.