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

• Published in: Chinese chemical letters 2024-07, Vol.35 (7), p.109019, Article 109019
• Main Authors: Li, Chuan, Han, Yangyang, Zhai, Yanan, Li, Ke, Liu, Xingzhong, Zhang, Zhuan, Jia, Cai, Che, Yongsheng
• Format: Article
• Language: English
• Subjects: Biosynthetic pathways; Cytotoxicity; Hetero-Diels–Alder; Phoma sp; Tropolonic sesquiterpenes
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2023.109019

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 Kα radiation. 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 4.85 µmol/L, while the co-isolated known meroterpenoid 4 displayed potent effects against three tumor cell lines, SUPB15, EL4, and H9, showing IC50 values of 0.36–27.08 µmol/L. Phomaketals A (1) and B (2), two tropolonic meroterpenoids with the unprecedented 5/7/11/6/6 and 5/6/11/6/6 pentacyclic skeletons, respectively, were isolated from the solid-substrate fermentation cultures of a eupC overexpressed mutant strain of Phoma sp. [Display omitted]