Study On The Secondary Metabolites Of Three Marine-derived Fungi

Marine fungi are very important microbial resources.Marine fungi can produce secondary metabolites with novel structure and strong activity due to its special living environment,and have become an important source of new drug research and development.In recent years,a large number of new compounds have been obtained from marine fungi,1567 new compounds were found from marine fungi from 2013 to 2017,except mangrove fungi,and most showed antitumor,antiviral and antibacterial activity.Since 1990,edible marine shellfishes are exceeding 75%of marine aquatic production in China has ranked first in the world.The current research on marine shellfishes mainly focus on the cultivation,pathogenic microbial detection,heavy metal accumulation and shellfish toxins.Molluscan shellfish concentrate microorganisms from surrounding waters during the filter-feeding process.Consequently,filter feeders are recognized as reservoirs for various microorganisms.However,up to now,the marine shellfish-associated fungi are virtually untouched and represent new promising sources of bioactive metabolites.This thesis studied the secondary matebolities of marine fungi monascus ruber BB5,Neosartorya pseudofischeri F27-1 and Aspergillus sp.XBB3.The compounds were purified using gel column chromatography,normal-phase silica gel column chromatography,thin-layer chromatography,C-18 reversed-phase silica gel column chromatography,and high performance liquid chromatography and recrystallization.The structures of the compounds were determined using NMR,MS,IR,UV,CD,X-ray single crystal diffraction and combination with literature search methods.13 compounds including three new compounds monarubins A–C（2-1,2-6 and 2-12）and together with four known alkaloids（2–5）,two isocoumarins（2-7,2-8）and four polyketides（2-9 to 2-11 and 2-13）were isolated from the Meretrix meretrix associated fungus monascus ruber BB5of marine shellfish.The absolute configurations of compounds 2-3,2-6 and2-12 were determined by ECD calculations.The NMR data of compounds（2-3）and（2-4）were first reported.Compounds 2-1–2-13 were evaluated for their cytotoxic activities against human nasopharyngeal carcinoma cell lines CNE1,CNE2,SUNE1 and HONE1 and hepatocellular carcinoma cell lines QGY7701 and HepG2.Monarubin B（2-6）displayed potent cytotoxicities against the cancer cell lines HepG2 and QGY7701 with IC₅₀values of 1.72 and 0.71μΜ,respectively.lunatinin（2-7）showed moderate cytotoxic activities against the cancer cell lines HepG2,QGY7701 and SUNE1 with the IC₅₀0 values of 9.60,7.12 and 28.12μΜ,respectively.Compounds 2-1 to 2-13 were isolated from Monascus ruber BB5 for the first time.11 alkaloids compounds were isolated from the marine fungus Neosartorya pseudofischeri F27-1.Among them,compounds cyclo（L-Pro-L-Leu）（3-1）、cyclo（L-Phenylalanyl-L-prolyl）（3-2）and dichocerazines A（3-5）were first isolated from Neosartorya pseudofischeri F27-1Five alkaloids compounds:nicotinic acid（4-1）,3-pyridinmethanol（4-2）,cyclo（Gly-L-Pro）（4-3）,cyclo-（-phenylalanyl-4-hydroxy-prolin）（4-4）,flazin（4-5）were isolated from the culture fluid of the marine-derived fungus Aspergillus sp.XBB3 from geoduck of marine shellfish,all of which were isolated from this fungus for the first time.In this paper,the secondary metabolites of three marine fungi were studied,and a total of 29 compounds were isolated,including 3 new compounds.The isolated structures included polyketones,alkaloids,and isocoumarins.Among them,2 strains fungi are derived from marine shellfish,which proves that marine shellfish assosiated fungi can produce compounds with diverse structures and good biological activities,which provides a theoretical and material basis for further research on marine shellfish assosiated fungi.