Isochromene metabolite from the facultative marine fungus Penicillium citrinum

Abstract

Facultative and obligative marine microscopic fungi are known to be promising sources of various types of biologically active compounds [1,2]. Under the auspices of a program for discovery of biologically active compounds in extracts of isolates of marine microscopic fungi, we isolated the strain Penicillium citrinum Thom. from sediment collected during core drilling of methane gas hydrates at a depth of 645 m in the Okhotsk Sea. The fungus was cultivated for 21 d at 22°C in a 1-L flask containing medium of composition sodium tartrate, 0.005 g; yeast extract, 0.01 g; rice, 10 g; KH 2 PO 4 , 0.005 g; and seawater, 20 mL.Fungal mycelium with medium was extracted twice with EtOAc. The extract was evaporated. The solid was dissolved in EtOH:H 2 O (1:4). The resulting solution was extracted successively by hexane, EtOAc, and BuOH. The EtOAc extract was evaporated in vacuo. The dry solid (300 mg) was chromatographed over a column (25 u 2 cm) of silica gel with elution by hexane:EtOAc (95:5) to afford a compound (8 mg). The compound was identified by MS and 2D NMR spectroscopy (Table 1) and comparison with the literature [3] as (3S)-3,5-dimethyl-8-methoxy-3,4-dihydro-1H-isochromen-6-ol (1). Compound 1, mp 122-123°C (hexane:EtOAc), [D] D 20 +118° (c 0.05, MeOH). Mass spectrum (m/z, %): 208 (100) [M] + , 193 (30) [M -CH 3 ] + , 177 (13) [M -CH 3 O] + , 164 (77), 149 (14), 134 (19), 119 (6), 91 (15), 77 (8).Compound 1 was isolated previously from the terrestrial fungi Penicillium expansum (grain) [4], P. sp. (freshwater isolate) [3], and Penicillium hybrid strains [5]. It is known to exhibit cytotoxic and anticoccidial activity [3]. It was isolated for the first time from a marine fungus.

Neuroprotective Activity of Some Marine Fungal Metabolites in the 6-Hydroxydopamin- and Paraquat-Induced Parkinson’s Disease Models

“…Together with melatonin-related 1 , the well-known fungal polyketides 3-methylorsellinic acid ( 2 ) and 8-methoxy-3,5-dimethylisochroman-6-ol( 3 ) were isolated from this fungus. Their structures were identified by comparing the NMR and MS data ( Figures S9–S13 ) with previously reported data [ 27 , 28 ].…”

Penicisteckins A–F, Isochroman-Derived Atropisomeric Dimers from Penicillium steckii HNNU-5B18

“…The 1 H and 13 C NMR data of 1 (Table 1) displayed two doublet methyls (δ H 1.37, H 3 -9, δ C 22.0, C-9; δ H 1.17, H 3 -9′, δ C 21.8, C-9′), one singlet methyl (δ H 2.11, H 3 -10, δ C 11.2, C-10), two methoxy (δ H 3.34, H 3 -11, δ C 60. . The COSY and HMBC spectra of 1 (Figure 1) revealed the presence of two sets of similar signals and allowed the construction of unit A (6-hydroxy-8-methoxy-3,5-dimethylisochroman moiety, 7) 22 and unit B (6-hydroxy-8-methoxy-3methylisochroman moiety), 16 which were confirmed by key HMBC correlations (Figure 1). The absence of protons H- Therefore, the planar structure of 1 was assigned as shown.…”

“…The COSY and HMBC correlations of 3 (Figure 1) revealed the presence of a unit of 6-hydroxy-8-methoxy-3,5-dimethylisochroman (7). 22 The deshielded C-7 (δ C 113.3) and the absence of the olefinic proton signal (δ H 6.29, H-7) in 3 suggested the linkage between C-7 and C-7′. The dimeric planar structure of 3 was unambiguously determined by the X-ray single-crystal diffraction analysis.…”

“…Known compounds 7 and 8 were structurally confirmed by comparison with literature data (Table S1). ,, Herein, we report their isolation, structure elucidation, plausible biosynthetic pathway, and bioactivities.…”

Major bioactive metabolites from marine fungi: A Review

“…Antibacterial and cytotoxic activities were reported from marine isolates of the fungal strain Myceliophthora lutea Costantin by Smetanina et al . (2011) [ 12 ]. Antimicrobial activity of marine fungi isolate was evaluated against six human pathogenic bacteria, they are Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Bacillus subtilis, Staphylococcus aureus and Klebsiella pneumoniae , with different solvents like n-butanol, chloroform, water and acetone.…”