Studies On Secondary Metabolites Of Aspergillus Versicolor And Penicillium Ochrochloron

As a huge population in nature,fungi have a wide variety of secondary metabolites and a wide range of biological activities.In recent decades,enormous secondary metabolites have been isolated from fungi,including alkaloids,steroids,lignans,coumarins and their derivatives,flavonoids,anthraquinones and terpenoids,etc.They have been research hotspots in the fields of natural products,chemical synthesis and biosynthesis.Most of these natural products have significant biological activities,such as antibacterial and antiviral,anti-inflammatory and analgesic,cytotoxic,cardiovascular,enzyme activated or inhibitory,insecticidal,etc.Therefore,a large number of secondary metabolites has been developed as drugs or as drug lead compounds to play an important value in drug development.Our research group has been engaged in the research of fungal secondary metabolites for a long time,and found many compounds with novel skeleton structure and show remarkable biological activities,some of which have potential prospects.For example,tremendously novel cytochalasins have been isolated from Aspergillus flavus and Chaetomium globosum,which have aroused great interest from experts of synthesis and biosynthesis.Asperterpenes A and B,isolated from Aspergillus terreus,have prominent BACE1 inhibitory activity,and asperterpene A may be a potential drug for treating Alzheimer’s disease(AD).Spiroaspertrione A with a novel architecture obtained from Aspergillus sp.TJ23 has a significant inhibitory effect on drug-resistant Staphylococcus aureus.Previously,our group studied the metabolites of Aspergillus versicolor from different sources,and linearly fused prenylated indole alkaloids,a series of novel alkaloids,were isolated.Therefore,in order to explore additionally unique linearly fused prenylated indole alkaloids,we focused our attention on Aspergillus versicolor derived from the soil of Qichun.Varieties of chromatographic separation methods,nuclear magnetic resonance(NMR)spectroscopies and mass spectrometries analyses,X-ray single crystal diffraction,as well as experimental and calculational ECD were used to isolate and identify,and 18 compounds were found,including six new compounds,account for four new linearly fused prenylated indole alkaloids,one new meroterpenoid and one new sesquiterpene.The cytotoxic activity of all isolated compounds were evaluated,and some showed moderate inhibitory activities.Compound 1(asperversiamide I),composed by an L-tryptophan and a rare natural D-proline,is an unreported C-11-spiro linearly fused prenylated indole alkaloid.The discovery of new linearly fused prenylated indole alkaloids further enriches the secondary metabolites of Aspergillus versicolor.Additionally,we also studied another strain of secondary metabolites of the wetland soil-derived fungus Penicillium ochrochloron from Yunnan province.Extensive literature research shows that the dominant secondary metabolite of Penicillium ochrochloron is brefeldin A(BFA).After isolation and structural elucidation,one new compound and four known compounds were found,including two sesquiterpenes,one alkaloid,one steroid,and one other type of compound.Among them,compounds 19 and 20 were the first reported compound from Penicillium ochrochloron.Finally,the author reviewed the research progress on the secondary metabolites of Aspergillus versicolor and their biological activities.The review showed that terpenes,alkaloids and polyketides are the main metabolites of A.versicolor.Therein,terpenoids have good antibacterial and antiviral activities,alkaloids have diverse skeletons,and some alkaloids have certain cytotoxic activities,and some polyketides show strong enzymes inhibitory activities and antibacterial activities.