Heptaketides from Corynespora sp. Inhabiting the Cavern Beard Lichen, Usnea cavernosa: First Report of Metabolites of an Endolichenic Fungus

Abstract

Two new heptaketides, corynesporol (1) and 1-hydroxydehydroherbarin (2), along with herbarin (3) were isolated from an endolichenic fungal strain, Corynespora sp. BA-10763, occurring in the cavern beard lichen Usnea cavernosa. The structures of 1−3 were elucidated from their spectroscopic data. Aerial oxidation of corynesporol (1) yielded herbarin (3). Acetylation of 1 afforded the naphthalene derivative 4, whereas acetylation of 3 gave the corresponding naphthoquinone 6 and dehydroherbarin (5). All compounds were evaluated for their cytotoxicity and ability to inhibit migration of human metastatic breast and prostate cancer cell lines MDA-MB-231 and PC-3M, respectively. Dehydroherbarin (5) inhibited migration of both cell lines at concentrations not toxic to these cell lines. This is the first report of metabolites from an endolichenic fungus.

Oxepinochromenones, Furochromenone, and their Putative Precursors from the Endolichenic Fungus Coniochaeta sp.

“…Conioxepinol B (2) was isolated as a white, amorphous solid with a molecular formula of C 16 The 1 H and 13 C NMR spectra of 2 showed resonances similar to those of 1, except that the C-11 methyl group (δ H /δ C 2.40/22.4) was replaced by an oxygenated methylene (δ H /δ C 4.70/63.8), which was confirmed by HMBC correlations from H 2 -11 to C-2, C-3, and C-4 and from the exchangeable proton at δ H 4.58 (OH-11) to C-3. Therefore, the gross structure of 2 was determined as shown.…”

“…Its elemental composition was determined to be C 16 pos. (Table 1) revealed the same chromenone unit as found in 1-3, but the resonances for the dihydrooxepine unit in 1 were significantly different from those for the remaining portion of 5.…”

“…DMAP (5.0 mg) and (S)-MTPA-Cl (10.0 µL, 0.052 mmol) were quickly added, the flask was sealed, and the mixture was stirred at room temperature for 12 h. The mixture was evaporated to dryness and purified by RP HPLC (Agilent Zorbax SB-C 18 column; 5 µm; 9.4 × 250 mm; 80% MeOH in H 2 O for 2 min, followed by 80-100% for 30 min; 2 mL/min) to afford 1a (0. In a similar fashion, a sample of 1 (1.5 mg, 0.004 mmol), CH 2 Cl 2 (3.0 mL), DMAP (5.0 mg), and (R)-MTPA-Cl (5.0 µL, 0.026 mmol) were allowed to react in a 10 mL round-bottomed flask at room temperature for 12 h, and the reaction mixture was processed as described above for 1a to afford 1b (1.2 mg): white powder; 1 Table 1; HMBC data (acetone-d 6 , 400 MHz) H-2 f C-1, 4, 9, 9a, 11; H-4 f C-1, 2, 3, 4a, 9, 9a, 11; H-5 f C-6, 7, 10a; H-6 f C-5, 7, 8; H-7 f C-6, 12; H-8 f C-6, 7, 8a, 9, 10a, 12; H 2 -11 f C-2, 3, 4; H 3 -13 f C-12; OH-1 f C-1, 2, 9a; OH-7 f C-6, 7, 8; OH-11 f C-3, 11; HRESIMS m/z 357.0578 (calcd for C 16 Table 1; HMBC data (acetone-d 6 , 400 MHz) H-2 f C-1, 4, 9, 11; H-4 f C-2, 4a, 9, 9a, 11; H-5 f C-6, 7, 10a; H-6 f C-5, 7, 8; H 3 -11 f C-2, 3, 4; H 3 -13 f C-12; OH-1 f C-1, 2, 3, 9a; OH-8 f C-8, 8a, 12; NOESY correlations (acetone-d 6 , 400 MHz) H-7 T H 3 -13; H 3 -13 T H-7; HRESIMS m/z 357.0582 (calcd for C 16 H 14 O 8 Na, 357.0581).…”

“…15 However, they are chemically underexplored, with only three species previously investigated. [16][17][18] During an ongoing search for new cytotoxic natural products from this unique source, the fungus Coniochaeta sp. (Coniochaetaceae) was subjected to our chemical study.…”

Endolichenic fungi: the lesser known fungal associates of lichens

“…Furthermore, like the endophytic fungi, they produce an array of secondary metabolites such as alkaloids, quinones, furanones, pyrones, benzopyranoids, xanthones, terpenes, steroids, peptides and allycylic compounds (Paranagama et al 2007; He et al 2012; Yang et al 2012, 2016; Li et al 2015; Samanthi et al 2015; Kellogg and Raja 2016; Yuan et al 2016). These metabolites exhibit many novel bioactivities including antibacterial, antifungal, cytotoxic and antioxidant activities (Kellogg and Raja 2016; Suryanarayanan et al 2017).…”