Pyrrolizilactone, a new pyrrolizidinone metabolite produced by a fungus

Microorganisms have a tremendous capacity for producing structurally diverse metabolites, which show various activities.¹ They are important sources of pharmaceutical leads and therapeutic agents,^{2, 3} and are also used as bioprobes in chemical biology for the exploration of biological functions.^{4, 5} To search for and discover such structurally unique metabolites efficiently and rapidly, we have constructed a microbial metabolite fraction library with a spectral database on the basis of photodiode array detector-attached LC/MS analysis.^{6, 7} Through our methodology for the construction of this fraction library, we discovered and identified a 16-membered macrolactam with an unusual β-keto-amide moiety, verticilactam,⁸ 6,6-spiroacetal polyketide, spirotoamides, A and B,⁹ the new fraquinocins, I and J,¹⁰ and 6-dimethylallylindole-3-carbaldehyde.¹¹ These results demonstrate the advantage of the fraction library in isolating novel metabolites from natural sources. We report herein the isolation of a novel compound from a fungi fraction library.

An 18-liter culture broth of an uncharacterized fungus was cultivated to obtain 16.1 g of an ethyl acetate-soluble extract. This was separated into eight fractions through a silica-gel column chromatography, with a stepwise gradient of CHCl₃/MeOH. The second fraction eluted with CHCl₃/MeOH (100:1) was further separated by chromatography using a Sephadex LH-20 column with CHCl₃/MeOH (1:1) to afford three fractions. The second fraction, showing an unidentified peak in LC/MS analysis, was purified by C₁₈-HPLC to afford a colorless amorphous solid (1, 5.5 mg). Colorless amorphous; [α]₅₈₉²⁶+5.9° (c 0.08, MeOH); UV (MeOH) λ_max (log ɛ) 209 (3.34), 236 (3.01) nm; IR (ATR) ν_max (cm⁻¹) 3410, 2920, 2875, 1790, 1715, 1685, 1575, 1450, 1375, 1335, 1280, 1160, 1110, 1020; ¹H NMR and ¹³C NMR data, see Table 1; HRESIMS m/z: 416.2433 [M+H]⁺ (calcd for C₂₄H₃₄NO₅: 416.2437).

Table 1 ¹H and ¹³C NMR chemical shifts with HMBC and NOESY correlations in CDCl₃

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