Metabolites of an Unidentified Fungus: a New 5,6-Dihydro-2-pyrone Related to Pestalotin

Abstract

Spectroscopic and chemical studies, including correlation with pestalotin (LL-P880a), show that a new metabolite isolated from cultures of an unidentified fungus is 5-hydroxy-3-methoxy-6-0x0-2-decenoic acid 6-lactone.Les Ctudes spectroscopiques et chimiques, contenant une correlation avec la pestalotine (LL-P880a), dCmontrent qu'un nouveau mitabolite, isolC de cultures d'un champignon nonidentifiC est le &-lactone de I'acide 5-hydroxy-3-mCthoxy-6-0x0-2-decenoique.Can. J. Chem., 52,825 (1974) Tamura and co-workers (1) recently described the isolation and structure elucidation of pestalotin (I), a new 5,6-dihydro-2-pyrone displaying gibberellin synergism, produced by the phytopathogenic fungus Pestalotia cryptomeriaecola. The same compound, designated LL-P880a, was isolated from an unidentified Penicillium species by Ellestad et al. (2), and these workers further demonstrated the configuration at C-6 and -1' to be S. We report here on the closely related substance 2 isolated, together with 1, from culture filtrates of an unidentified fungus. ' The new metabolite, C , ,Hl,O4, displayed i.r. absorption (CCI,) at 1728 and 1630 cm-' and U.V. I , , , 233 nm ( E 10 600). These features, together with n.m.r. signals corresponding to an olefinic hydrogen at 6 5.17 (lH, s) and methyl ether protons at 6 3.78 (3H, s), suggested a 4-methoxy-5,6-dihydro-2-pyrone (1-5). In the mass spectrum, the base peak at m/e 127 (M' -85) and an ion at mle 85 (C5H90+) result from cleavage of an n-pentanoyl chain; further evidence for this structural element was found in the i.r. absorption at 1740 crn-' (CO), and the appropriate methyl and methylene signals in the 220 MHz n.m.r. spectrum. A signal at 6 4.80 (IH, dd, J,, + J,, -14 Hz) was attributed to the C-6 hydrogen by virtue of its low-field IThe fact that the organism could not be induced to sporulate has rendered identification impossible so far but suggests that it is neither a Pestalotia nor a Penicillium species. We thank Dr. L. P. Magasi of this laboratory for providing the culture, IT-6, and for discussions relating to its identification. position and m~ltiplicity,~ and this assignment also defines the location of the side chain. These data are readily interpreted in terms of structure 2. C H 3 y 3Conversion of 2 into the corresponding pyrone, 3, corroborated the assigned formulation. This transformation was effected directly (without isolation of a bromine-containing intermediate) by treatment of 2 with N-bromosuccinimide. To facilitate comparison with a simple model, 4-methoxy-6-methyl-2-pyrone, the carbonyl group in the side chain of 3 was reduced with sodium borohydride. The spectroscopic characteristics of the product, 4, indeed showed a gratifying similarity to those of the model a-pyrone. Thus, 4 displayed (besides broad hydroxyl absorption at 3390 cm-') i.r. peaks (CC1,) at 1737, 1650, and 1242 cm-' ; and U.V. I , , , (EtOH) 211 ( E 7420) and 282 nm 'The signal for the C-6 proton changed in a manner consistent with the assigned structure on reduction of the ketone func...

Phytotoxic α-pyrones produced by Pestalotiopsis guepinii, the causal agent of hazelnut twig blight

“…4 The ESIMS spectrum of 2 showed, beside the sodium cluster and the pseudomolecular ion at m/z 277 [M+Na]+, 255 [M+H]+, the significant fragmentation peak at m/z 195 [M+H-AcOH]+, which was generated by the pseudomolecular ion through the typical loss of the acetic acid residue. 9 The oxidized derivative of 3 showed IR, UV and 1 H NMR data very similar to those previously reported in the literature for the product obtained by the reaction of N-bromosuccinimide with the 5-hydroxy-3-methoxy-6-oxo-2-decenoic acid d-lactone, a metabolite isolated from an unidentified fungus 10 and close related to the monosubstituted 5,6-dihydro-a-pyrone pestalotin. This latter compound is a fungal metabolite with giberellin synergistic activity isolated originally from the phytopathogenic fungus Pestalotia cryptomeriaecola 11,12 and successively from a Penicillum sp.…”

Evaluation of culture media for the production of secondary metabolites in a natural products screening program

“…Aurofusarin is a mycotoxin and red pigment common in Fusarium species (Ezekiel et al , 2012 ; Soerensen et al , 2012 ; Mikusova et al , 2013 ). PC3 is an analog of pestalotin, which was first described as a product of an unidentified fungus in 1973 (Strunz et al , 1974 ); pestalotins synergistically augment the plant hormone gibberellin (Kimura et al , 1971 ; Kimura et al , 1977 ; Kirihata et al , 1996 ). While the structural diversity of compounds from fungi can be vast (El-Elimat et al , 2012 ), these were chosen as representative compounds for a drug screening program, since they contain heteroatoms, conjugated rings, carbonyl groups, hydroxy, methoxy, and methyl moieties, and polyketide derived chains.…”

Identification and characterization of compounds from Chrysosporium multifidum, a fungus with moderate antimicrobial activity isolated from Hermetia illucens gut microbiota

“…Bioguided analysis of the ethyl acetate extract of C . multifidum broth resulted in the isolation of 4-methoxy-2H-pyran-2-one ( 1 ) [20], 4-methoxy-6-pentyl-2H-pyran-2-one ( 2 ) [21], 6-(1-hydroxypentyl)-4-methoxy-pyran-2-one ( 3 ) [21,22], 6-[8-propyloxiran-1-yl]-4-methoxy-pyran-2-one ( 4 ) [23], pestalotin ( 5 ) [24,25], 5,6-dihydro-4-methoxy-6-(pentanoyloxy)-2H-pyran-2-one ( 6 ) [22,25] and cyclo-(L-Pro-L-Val) ( 7 ) [26]. All the compounds (Fig 2) were identified by comparison of their spectroscopic data (HRMS and 1 H and 13 C NMR) with literature-reported values, as well as careful examination of their 2D NMR spectra (COSY, HSQC, HMBC).…”