Phomaketals A and B,pentacyclic meroterpenoids from a eupC overexpressed mutant strain of Phoma sp.  

作　　者：Chuan Li Yangyang Han Yanan Zhai Ke Li Xingzhong Liu Zhuan Zhang Cai Jia Yongsheng Che 

机构地区：[1]NHC Key Laboratory of Biotechnology of Antibiotics,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China [2]State Key Laboratory of Toxicology&Medical Countermeasures,Beijing Institute of Pharmacology&Toxicology,Beijing 100850,China [3]Department of Microbiology,College of Life Sciences,Nankai University,Tianjin 300071,China

出　　处：《Chinese Chemical Letters》2024年第7期350-354,共5页中国化学快报（英文版）

基　　金：financial support from the National Natural Science Foundation of China(No.82003628);the CAMS Innovation Fund for Medical Sciences(Nos.2021-I2M-1-030,2021-I2M-1-028,and 2021-1-I2M-2-002)。

摘　　要：Phomaketals A(1)and B(2),two tropolonic meroterpenoids with the unprecedented pentacyclic skeletons,were isolated from the solid-substrate fermentation cultures of a eupC overexpressed mutant strain of the fungus Phoma sp.,together with a biogenetically related secondary metabolite pughiinin B(3),and the known one noreupenifeldin B(4).The structures of 1–3 were elucidated primarily by nuclear magnetic resonance(NMR)experiments.The absolute configurations of 1 and 2 were assigned by electronic circular dichroism calculations and the calculated NMR with DP4+analysis,while that of 3 was established by single-crystal X-ray diffraction analysis using Cu Kαradiation.Biogenetically,phomaketals A(1)and B(2)could be derived from the hypothetical tropolonic sesquiterpene intermediates neosetophomone B(6)and 9-R-neosetophomone B(6),respectively,via different reactions cascades.Compound 1 showed antiproliferative effect only against the SUPB15 cells,with an 50%inhibitory concentration(IC50)value of 4.85μmol/L,while the co-isolated known meroterpenoid 4 displayed potent effects against three tumor cell lines,SUPB15,EL4,and H9,showing IC50values of 0.36–27.08μmol/L.

关 键 词：Phoma sp. Tropolonic sesquiterpenes Biosynthetic pathways Hetero-Diels–Alder CYTOTOXICITY 

分 类 号：R914[医药卫生—药物化学] O629.61[医药卫生—药学]