A sesquiterpene compound from a zingiber officinale endophytic fungus, a preparation method and application thereof

Abstract

The application discloses a sesquiterpene compound from an endophytic fungus of Alpinia speciosa, a preparation method and application. The application separates 7-butyl-4-methoxyoxepin-2(5H)-one with antibacterial activity from liquid fermentation culture of endophytic fungus Xylaria curta YSJ-5 of Alpinia speciosa, as shown in formula (I). The 7-butyl-4-methoxyoxepin-2(5H)-one is a new sesquiterpene compound, and shows good antibacterial activity to MRSA and SA, and the MIC value is 6.3 mu g / mL. The application provides a candidate drug for researching and developing a new antibacterial drug, and provides a scientific basis for developing and utilizing the endophytic fungus resource of Alpinia speciosa.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of medicine and biotechnology, and particularly relates to a sesquiterpene compound from an endophytic fungus of Zingiber striolatum, a preparation method and application. BACKGROUND

[0002] In the clinical field, infections caused by microorganisms such as bacteria and fungi have a high incidence and mortality, and these infections pose a serious challenge to human drug resistance. Since 1960, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) have become common pathogens that cause potentially fatal diseases in healthcare facilities and community environments (Rajput et al., 2021; Huang et al., 2024; Lawal et al., 2022; Azzam et al., 2023). These infectious diseases include severe soft tissue and bone infections, endocarditis, and pneumonia, and are key factors leading to high morbidity and mortality (Turner et al., 2019; Xiao et al., 2022). Each year, tens of thousands of people die from MRSA infections, causing a huge economic burden on patients and putting tremendous pressure on global medical resources.

[0003] Currently, the World Health Organization has listed MRSA infection as one of the major global clinical challenges (Cascioferro et al., 2021). The drugs used to treat MRSA infection are very limited, and vancomycin is considered the drug of choice (Wu et al., 2021). However, due to the abuse of vancomycin, drug-resistant strains have emerged. Vancomycin has strong toxic side effects, which limits its clinical application (Tsutsuura et al., 2021), therefore, there is an urgent need in the global medical field to find and develop new antibiotic drugs to cope with the ongoing public health challenge (Schillaci et al., 2017).

[0004] Endophytic fungal species are rich and diverse, they are in a special environment inside plants, and can produce various structures of secondary metabolites, the structural types of their compounds far exceed the range of plant metabolites, it is easy to find novel structural compounds from them, and they have various biological activities, therefore, endophytic fungi have become an important resource for discovering new natural active substances, and have important application potential in agriculture and pharmaceutical industry.

[0005] Alpinia zerumbet, a plant of Zingiberaceae Alpinia, is well known for its multi-functionality and high value, not only as an ornamental plant to add beauty to gardens and indoor, but also has important medicinal value. Further, Alpinia zerumbet has attracted much attention due to its significant pharmacological effects in antibacterial (Victório et al., 2009), insecticidal (Kerdudo et al., 2017), acaricidal (Bressanin et al., 2021), antioxidant (Kuraya et al., 2017), vasodilatory (Rocha et al., 2023), hypotensive (Lahlou et al., 2003) and cancer cell proliferation inhibition (Liang Kun et al., 2022). SUMMARY

[0006] The purpose of the present application is to overcome the deficiencies of the prior art, and to provide a new compound 7-butyl-4-methoxyoxepin-2(5H)-one with antibacterial activity discovered from Alpinia zerumbet endophytic fungi, as well as a preparation method and application thereof.

[0007] The first purpose of the present application is to provide a compound 7-butyl-4-methoxyoxepin-2(5H)-one as shown in formula (I),

[0008]

[0009] The second purpose of the present application is to provide a preparation method of the compound 7-butyl-4-methoxyoxepin-2(5H)-one, which is prepared from the fermentation culture of Alpinia zerumbet endophytic fungi Xylaria curta YSJ-5.

[0010] Preferably, the preparation method comprises the following steps:

[0011] a. preparing a solid fermentation culture of Alpinia zerumbet endophytic fungi Xylaria curta YSJ-5, extracting the solid fermentation with ethyl acetate, and obtaining an extract after concentrating the extract;

[0012] b. treating the crude extract (30.3g) by reverse phase silica gel column chromatography, using methanol: water (30:70→100:0, v / v) and methanol: acetone (10:1→1:1, v / v) as elution system for gradient elution. This process isolates 5 components: AY-1 (4.3g), BY-2 (5.8g), CY-3 (3.0g), DY-4 (8.4g) and EY-5 (8.6g).

[0013] Component DY-4 (8.4 g) was subjected to normal phase column chromatography with a gradient elution system of dichloromethane:methanol (100:1→1:1, v / v) to obtain 6 sub-components: DY-4-1 (0.1 g), DY-4-2 (1.1 g), DY-4-3 (1.2 g), DY-4-4 (1.0 g), DY-4-5 (1.0 g), DY-4-6 (1.2 g). First, DY-4-1 was subjected to Sephadex LH-20 gel column chromatography with a gradient elution system of dichloromethane:methanol (1:3, v / v) to obtain 2 fractions: DY-4-1-1 (0.07 g) and DY-4-1-2 (0.03 g). Component DY-4-1-1 with Rf = 0.5-0.6 in TLC thin layer chromatography developed with n-hexane:ethyl acetate = 2:1 (v / v) was subjected to normal phase column chromatography with a gradient elution system of petroleum ether:ethyl acetate (5:1→2:1, v / v), and then further purified by reversed-phase semi-preparative high performance liquid chromatography with a gradient elution system of MeCN / H2O (50:50, v / v, 2 mL / min) to obtain 7-butyl-4-methoxyoxepin-2(5H)-one (3.0 mg), which had Rf = 0.4-0.5 in TLC thin layer chromatography developed with n-hexane:ethyl acetate = 2:1 (v / v).

[0014] Preferably, the compound 7-butyl-4-methoxyoxepin-2(5H)-one is obtained by further semi-preparative HPLC of component DY-4-1-1 using a YMCpack ODS-A / AQ column with a mobile phase of acetonitrile / water (50:50, v / v) at a flow rate of 2 mL / min, and the compound 7-butyl-4-methoxyoxepin-2(5H)-one is obtained at t R 19 min.

[0015] Preferably, the step a of preparing the fermentation culture of the endophytic fungus Xylaria curta YSJ-5 comprises the following steps: under sterile conditions in a clean bench, the YSJ-5 strain is inoculated into a sterilized liquid medium. After inoculation, the strain is cultured in a constant temperature shaker at 28°C and 120 r / min for 5 days to obtain a seed liquid. Then, each 25 mL of the seed liquid is inoculated into a 1000 mL conical flask containing 500 mL of liquid medium, and a total of 160 conical flasks are prepared for large-scale fermentation. These conical flasks are continuously cultured in a shaker at 28°C and 120 r / min for 7 days to obtain a liquid fermentation product. The collected liquid fermentation product is filtered through 4 layers of gauze to remove mycelium, and then the filtrate is extracted with ethyl acetate, and the organic phase is concentrated by reduced pressure concentration treatment to obtain about 30.3 g of YSJ-5 crude extract.

[0016] A third object of the present application is to provide the use of the compound 7-butyl-4-methoxyoxepin-2(5H)-one, or a pharmaceutically acceptable salt thereof, in the manufacture of an antibacterial medicament.

[0017] Preferably, the antibacterial medicament is an anti-Staphylococcus aureus and methicillin-resistant Staphylococcus aureus medicament.

[0018] Preferably, the antibacterial medicament is an anti-Staphylococcus aureus and methicillin-resistant Staphylococcus aureus medicament.

[0019] A fourth object of the present application is to provide an antibacterial medicament comprising an effective amount of the compound 7-butyl-4-methoxyoxepin-2(5H)-one, or a pharmaceutically acceptable salt thereof, as an active ingredient, and a pharmaceutically acceptable carrier.

[0020] The present application also provides the use of the endophytic fungus Xylaria curta YSJ-5 in the preparation of the compound 7-butyl-4-methoxyoxepin-2(5H)-one.

[0021] The present application has found, through experiments, that the compound 7-butyl-4-methoxyoxepin-2(5H)-one has good inhibitory activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus, with a MIC value of 6.3 μg / mL, and has no cytotoxicity, while the MIC values of the positive control drug vancomycin are 0.63 and 1.3 μg / mL, respectively. This result shows that the compound 7-butyl-4-methoxyoxepin-2(5H)-one of the present application has relatively significant antibacterial activity.

[0022] The endophytic fungus Xylaria curta YSJ-5 of the present application has been disclosed in Wei SS, Lai JY, Chen C, Zhang YJ, Nong XM, Qiu KD, Duan FF, Zou ZX, Tan HB. Sesquiterpenes and α-pyrones from an endophytic fungus Xylaria curta YSJ-5. Phytochemistry, 2024, 220:114011 [i.e. the strain Xylaria curta in this document], and the applicant also holds the strain, which is preserved in the Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement, South China Botanical Garden, Guangzhou, and is guaranteed to be provided to the public for 20 years from the date of application. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 is the compound 7-butyl-4-methoxyoxepin-2(5H)-one 1 H-NMR spectrum;

[0024] Figure 2 is the compound 7-butyl-4-methoxyoxepin-2(5H)-one 13 C-NMR spectrum;

[0025] Figure 3 COSY spectrum of the compound 7-butyl-4-methoxyoxepin-2(5H)-one;

[0026] Figure 4 HSQC spectrum of the compound 7-butyl-4-methoxyoxepin-2(5H)-one;

[0027] Figure 5 HMBC spectrum of the compound 7-butyl-4-methoxyoxepin-2(5H)-one;

[0028] Figure 6 NOESY spectrum of the compound 7-butyl-4-methoxyoxepin-2(5H)-one;

[0029] Figure 7 is the structure of the compound 1 and 1 H- 1 H COSY and HMBC correlation signals. DETAILED DESCRIPTION

[0030] The following examples are further illustrations of the present application and are not intended to limit the present application.

[0031] Example 1:

[0032] I. Isolation, purification and identification of endophytic fungus Xylaria curta YSJ-5 from Alpinia speciosa

[0033] The endophytic fungus YSJ-5 of the present application was isolated from the leaves of Alpinia speciosa plants collected from the South China Botanical Garden in Guangzhou, Guangdong Province in December 2020. After ITS sequence analysis and identification, blast comparison and homology analysis, the strain was identified as Xylaria curta, named Xylaria curta YSJ-5 (hereinafter referred to as strain YSJ-5).

[0034] II. Solid-state fermentation of strain YSJ-5

[0035] Under sterile conditions on a clean bench, the YSJ-5 strain was transferred to a sterilized PDB liquid medium. After inoculation, the strain was cultured in a constant temperature shaker at 28°C and 120 r / min for 5 days to obtain a seed liquid. Subsequently, 25 mL of seed liquid was inoculated into each 1000 mL conical flask containing 500 mL of liquid medium, and a total of 160 conical flasks were prepared for large-scale fermentation. These conical flasks were continuously cultured in a shaker at 28°C and 120 r / min for 7 days to obtain the liquid fermentation product. The collected liquid fermentation product was filtered through 4 layers of gauze to remove mycelium, then the filtrate was extracted with ethyl acetate, and the organic phase was concentrated by reduced pressure concentration treatment to obtain about 30.3 g of YSJ-5 crude extract

[0036] III. Preparation of compound 7-butyl-4-methoxyoxepin-2(5H)-one

[0037] The YSJ-5 crude extract (30.3 g) was treated by reverse phase silica gel column chromatography, using methanol: water (30:70→100:0, v / v) and methanol: acetone (10:1→1:1, v / v) as elution systems for gradient elution. This process isolated 5 components: 30:70 methanol water polar segment AY-1 (4.3 g), 50:50 methanol water polar segment BY-2 (5.8 g), 70:30 methanol water polar segment CY-3 (3.0 g), 90:10 methanol water polar segment DY-4 (8.4 g), and the remaining polar segment EY-5 (8.6 g).

[0038] 90:10 methanol / water polar fraction component DY-4 (8.4 g) was subjected to normal phase column chromatography, elution system was dichloromethane:methanol (100:1→1:1, v / v) gradient elution, to obtain 6 sub-components: 100:1→10:1 polar fraction DY-4-1 (0.1 g), 5:1 polar fraction DY-4-2 (1.1 g), 4:1 polar fraction DY-4-3 (1.2 g), 3:1 polar fraction DY-4-4 (1.0 g), 2:1 polar fraction DY-4-5 (1.0 g), 1:1 polar fraction DY-4-6 (1.2 g). First, 100:1→10:1 polar fraction DY-4-1 was subjected to Sephadex LH-20 gel column chromatography, using dichloromethane:methanol (1:3, v / v) as elution system, to isolate 2 parts DY-4-1-1 (0.07 g) and DY-4-1-2 (0.03 g). Component DY-4-1-1 with Rf=0.5-0.6 in TLC thin layer chromatography developed with n-hexane:ethyl acetate=2:1 (v / v) was subjected to normal phase column chromatography, using petroleum ether:ethyl acetate (5:1→2:1, v / v) gradient elution, and then further purified by reversed-phase semi-preparative high performance liquid chromatography, using YMC pack ODS-A / AQ column, elution condition was (MeCN / H2O, 50:50, v / v, 2 mL / min), to isolate 7-butyl-4-methoxyoxepin-2(5H)-one (3.0 mg, t R =19 min), TLC thin layer chromatography developed with n-hexane:ethyl acetate=2:1 (v / v) Rf=0.4-0.5.

[0039] IV. Structural identification of compound 7-butyl-4-methoxyoxepin-2(5H)-one

[0040] 1 H NMR, 13 C NMR, HMBC nuclear magnetic resonance spectra were determined by Bruker Advance-500 nuclear magnetic resonance spectrometer, using tetramethylsilane (TMS) as internal standard; ESI-MS data were determined by VGAutospec-3000 mass spectrometer.

[0041] As shown in Figures 1-6 , the Figure 1 H-NMR spectrum of compound 7-butyl-4-methoxyoxepin-2(5H)-one 1 Figure 2 C-NMR spectrum of compound 7-butyl-4-methoxyoxepin-2(5H)-one 13 Figure 3 ​​This is the COSY spectrum of compound 7-butyl-4-methoxyxepin-2(5H)-one; Figure 4 This is the HSQC spectrum of compound 7-butyl-4-methoxyoxepin-2(5H)-one; Figure 5 This is the HMBC spectrum of compound 7-butyl-4-methoxyoxepin-2(5H)-one; Figure 6 This is the NOESY spectrum of compound 7-butyl-4-methoxyoxepin-2(5H)-one.

[0042] Compound 1 (7-butyl-4-methoxyoxepin-2(5H)-one): colorless oil. 1 The 1H NMR spectrum (Table 1) shows that the signal of one methyl proton [δ] H 0.90 (t, J = 7.0 Hz, 3H)], 1 methoxy proton signal [δ H 3.79 (s, 3H)], 2 olefin proton signals [δ H 5.23 (d, J = 1.3 Hz, 1H), 6.07 (dd, J = 2.5, 4.6 Hz, 1H)]. Combined with its... 13 C10 NMR and HSQC data (Table 1) show that there are 11 carbon signals in the structure of this compound, including one methyl carbon signal [δ]. C 13.8 (C-11)], 1 oxygen-methyl carbon signal [δ C 56.3(C-4b)], 4 methylene carbon signals [δ C 33.9(C-8), 32.0(C-5), 26.7(C-9), 22.2(C-10)], two double-bonded methylene carbon signals [δ C 90.3(C-3), 89.9(C-6)], 3 quaternary carbon signals [δ C 171.7(C-7),169.8(C-4a),164.0(C-2)].

[0043] In the HMBC spectrum ( Figure 7 ), Observed correlations from H-3 to C-4 and C-5, H2-5 to C-4 and C-6, H-6 to C-2 and C-4, and H3-4b to C-4a, combined with 1 H- 1 The correlation signal of H-6 / H2-5 in the 1H COSY spectrum indicates that this compound has a seven-membered cyclic oxepin-2-one skeleton (Fernández-García et al., 2013). 1 H-1 In the COSY spectrum, another spin coupling system H3-11 / H2-10 / H2-9 / H2-8 was observed, indicating that the four carbon atoms C-11 / C-10 / C-9 / C-8 are directly connected. In the HMBC spectrum, the correlation signals of H2-9 to C-7, C-8 and C-10, and H2-8 to C-7 indicated that the side chain is attached to C-7. Thus, the structure of compound 1 was deduced and named as 7-butyl-4-methoxyoxepin-2(5H)-one.

[0044] Table 1 NMR data of compound 7-butyl-4-methoxyoxepin-2(5H)-one (δ in ppm, J in Hz, CDC13)

[0045]

[0046]

[0047] Thus, the chemical structure of compound 1 (7-butyl-4-methoxyoxepin-2(5H)-one) is determined as shown in formula (I).

[0048]

[0049] Example 2:

[0050] 1. Experimental method: Vancomycin and polymyxin B were used as positive control drugs. The micro-broth dilution method was used to evaluate the antibacterial activity of 7-butyl-4-methoxyoxepin-2(5H)-one against Staphylococcus aureus (SA, CMCC 26003), methicillin-resistant Staphylococcus aureus (MRSA, JCSC 3063) and Escherichia coli (E. coli, ATCC 8739). The resazurin colorimetric method was used as an intuitive indicator to determine the minimum inhibitory concentration (MIC) value of the compound (Wang M, Zhao L, Chen K, et al., 2020. Antibacterial sesquiterpenes from the stems and roots of Thuja sutchuenensis [J]. Bioorganic Chemistry, 96: 103645). Resazurin, a blue non-fluorescent dye, can be converted to pink by reductase in living cells, while cells lacking activity cannot cause color change and remain blue. This color change provides a convenient visual identification method for evaluating the antibacterial activity of the compound. Using the 96-well plate gradient dilution method, the MIC values of multiple compounds were determined simultaneously under the same experimental conditions. The specific experimental steps are as follows:

[0051] 1. Dissolve the test compound in DMSO reagent and prepare a 1 mg / mL solution. For the positive control group, use sterile water to prepare vancomycin and polymyxin B to the same concentration.

[0052] 2. Take SA, MRSA and E. coli strains stored in 30% glycerol cryotubes from the refrigerator, use a pipette to take 200 μL of bacterial solution and add it to sterilized Mueller-Hinton Broth medium. Then, place it in a constant temperature shaker set at 37°C overnight to activate for subsequent experiments.

[0053] 3. Take the activated MHB medium containing the bacterial solution and use a UV spectrophotometer to determine the concentration (OD) value of the bacterial solution. Dilute the bacterial solution with medium to an OD value of 0.07, at which the bacterial concentration is 1.25 x 10 600 CFU / mL (referred to as solution A) for subsequent antibacterial experiments. 6

[0054] 4. Dilute the resazurin indicator with sterile water to 0.1 mg / mL to prepare a sterile aqueous solution (referred to as solution B).

[0055] ​5. Mix solution A and solution B in the ratio of 3:2 by volume, ensuring uniform mixing (denoted as solution C). The MIC value of the compound is then determined using the two-fold dilution method.

[0056] 6. Add 180 μL of solution C to the first row of the 96-well culture plate, and 100 μL to the remaining rows. Add 20 μL of the prepared compound sample and positive control to the first row of wells, set 2 parallel wells for each sample, and sequentially dilute.

[0057] After the sample is added, place the 96-well plate in a 37°C constant temperature incubator for 9 h, monitor and record the color change of the indicator in the plate to determine the MIC value.

[0058] 2. Experimental results: The prepared compound 7-butyl-4-methoxyoxepin-2(5H)-one showed good antibacterial activity against MRSA and SA, with MIC values of 6.3 μg / mL (the MIC values of the positive control drug vancomycin were 0.63 and 1.3 μg / mL, respectively) (Table 2). This result indicates that the compound 7-butyl-4-methoxyoxepin-2(5H)-one has significant antibacterial activity, and therefore, the present application provides a candidate compound for the research and development of new antibacterial drugs, and provides a scientific basis for the development and utilization of natural active substances of plant endophytic fungi.

[0059] Table 2: Antibacterial activity data (MIC, μg / mL) of the compound 7-butyl-4-methoxyoxepin-2(5H)-one

[0060]

Claims

1. A compound of formula (I) 7-butyl-4-methoxyoxepin-2(5 H )-one, Formula (I) 2. A process for the preparation of the compound 7-butyl-4-methoxyoxepin-2(5 H )-one, characterized in that it is From endophytic fungi of Alpinia speciosa Hance Xylaria curta The fermentation culture of YSJ-5 is isolated and prepared, comprising the following steps: a. Preparation of Alpinia speciosa endophytic fungus Xylaria curta The solid fermentation culture of YSJ-5 was extracted with ethyl acetate, and the extract was concentrated to obtain a crude extract. b. The crude extract 30.3 g was subjected to column chromatography on reversed-phase silica gel using methanol:water 30:70→100:0, v / v and methanol:acetone 10:1→1:1, v / v as eluting system for gradient elution, and five fractions were isolated: AY-1 4.3 g, BY-2 5.8 g, CY-3 3.0 g, DY-4 8.4 g and EY-5 8.6 g; Component DY-4 8.4 g was subjected to normal phase column chromatography using a gradient elution system of dichloromethane:methanol 100:1→1:1, v / v to obtain 6 sub-components: DY-4-1 0.1 g, DY-4-2 1.1 g, DY-4-3 1.2 g, DY-4-4 1.0 g, DY-4-5 1.0 g, DY-4-6 1.2 g. First, DY-4-1 was subjected to Sephadex LH-20 gel column chromatography using dichloromethane:methanol 1:3, v / v as the elution system to isolate 2 fractions, DY-4-1-1 0.07 g and DY-4-1-2 0.03 g. TLC thin layer chromatography was performed using n-hexane:ethyl acetate = 2:1 v / v to develop the component DY-4-1-1 with Rf = 0.5-0.

6. DY-4-1-1 was subjected to normal phase column chromatography using a gradient elution system of petroleum ether:ethyl acetate 5:1→2:1, v / v, followed by further purification using reverse phase semi-preparative high performance liquid chromatography with elution conditions of MeCN / H2O, 50:50, v / v, 2 mL / min to isolate 7-butyl-4-methoxyoxepin-2(5 H )-one 3.0 mg, TLC thin layer chromatography was performed using n-hexane:ethyl acetate = 2:1 v / v to develop Rf = 0.4-0.

5.

3. The preparation method according to claim 2, characterized in that, The component DY-4-1-1 was further purified by semi-preparative HPLC to obtain compound 7-butyl-4-methoxyoxepin-2(5 H )-one using a YMC pack ODS-A / AQ column with a mobile phase of acetonitrile / water 50:50 by volume at a flow rate of 2 mL / min to obtain compound 7-butyl-4-methoxyoxepin-2(5 H )-one, t R 19 min. 19 min.

4. The preparation method according to claim 2, characterized in that, The fermentation culture of the prepared Alpinia speciosa endophytic fungus of step a Xylaria curta YSJ-5 comprises the following steps: under a sterile condition in a super-clean bench, the YSJ-5 strain is transferred to a sterilized liquid culture medium, after inoculation, the strain is cultured in a constant-temperature shaker under the condition of 28 o C and 120 r / min for 5 days to obtain a seed liquid, then 25 mL of the seed liquid is inoculated into each 1000 mL conical flask containing 500 mL of the liquid culture medium, a total of 160 conical flasks are prepared for large-scale fermentation, and the conical flasks are continuously cultured in a shaker under the condition of 28 o C and 120 r / min for 7 days to obtain a liquid fermentation product, the collected liquid fermentation product is filtered through 4 layers of gauze to remove mycelium, then the filtrate is extracted using ethyl acetate, and the organic phase is concentrated by reduced-pressure concentration treatment to finally obtain about 30.3 g of a YSJ-5 crude extract.

5. Use of the compound 7-butyl-4-methoxyoxepin-2(5 H )-one, or a pharmaceutically acceptable salt thereof, for the manufacture of an antibacterial medicament, which is an anti- S. aureus and anti-MRSA medicament.

6. An antibacterial agent, characterized by, comprising an effective amount of the compound 7-butyl-4-methoxyoxepin-2(5 H )-one, or a pharmaceutically acceptable salt thereof, as an active ingredient, and a pharmaceutically acceptable carrier.

7. The antibacterial agent of claim 6, wherein The antibacterial drug is an anti-staphylococcus aureus and methicillin-resistant staphylococcus aureus drug.

8. An endophytic fungus of Alpinia speciosa Xylaria curta Use of YSJ-5 in the preparation of the compound 7-butyl-4-methoxyoxepin-2(5H)-one according to claim 1.

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