Helvolic Acid Derivatives with Antibacterial Activities against Streptococcus agalactiaefrom the Marine-Derived Fungus Aspergillus fumigatusHNMF0047

Streptococcus agalactiaeis a hazardous pathogen that can cause great harm to humans and fish. In the present study, the known fungal metabolite helvolic acid (10), seven new helvolic acid derivatives named 16-O-deacetylhelvolic acid 21,16-lactone (2), 6-O-propionyl-6,16-O-dideacetylhelvolic acid 21,16-lactone (3), 1,2-dihydro-6,16-O-dideacetylhelvolic acid 21,16-lactone (4), 1,2-dihydro-16-O-deacetylhelvolic acid 21,16-lactone (5), 16-O-propionyl-16-O-deacetylhelvolic acid (6), 6-O-propionyl-6-O-deacetylhelvolic acid (7), and 24-epi-6β,16β-diacetoxy-25-hydroxy-3,7-dioxo-29-nordammara-1,17(20)-diene-21,24-lactone (9), and two known ones (1and 8) were isolated from the marine-derived fungus Aspergillus fumigatusHNMF0047 obtained from an unidentified sponge from Wenchang Beach, Hainan Province, China. The structures and the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data and electronic circular dichroism (ECD) spectroscopic analyses along with quantum ECD calculations. In addition, the spectroscopic data of compound 1are reported here for the first time, the configuration of C-24 of known compound 8was revised based on comparison of its ROESY data with its C-24 epimer 9, and the absolute configuration of 8was also determined for the first time. Compounds 6, 7, and 10showed stronger antibacterial activity than a tobramycin control against S. agalactiaewith MIC values of 16, 2, and 8 μg/mL, respectively.