Mangrove forest-sourced myrothecium peritoneum and method for preparing benzofuran antibiotics by using myrothecium peritoneum

Abstract

The invention discloses mangrove forest-sourced rhodophyllum and a method for preparing benzofuran antibiotics by using the rhodophyllum, and relates to the field of industrial microorganisms. According to the present invention, the mangrove forest source-sourced rhodophyllum SCSIO 41432 can produce the benzofuran antibiotics such as the stribengal A (1), the stribengal B (2), the stribengal C (3), the stribengal D (4), the stribengal E (5), the stribengal H (6) and the stribengal I (7), and the seven antibiotics can be prepared by using the rhodophyllum, such that the new method is provided for the production and the preparation of the seven antibiotics.

Description

Technical field:

[0001] The invention belongs to the field of industrial microorganisms, and specifically relates to a mangrove sediment-derived fungus Striaticonidium cinctum SCSIO 41432 (GDMCC NO.65653) capable of producing benzofuran antibiotics and a method for preparing benzofuran antibiotics by fermentation using the fungus. Background technology:

[0002] Benzofuran is composed of a benzene ring and a furan ring, and its derivatives usually contain some other structural units, such as benzene, pyran, furan, or they may form a benzofuran-based heterocycle. Benzofuran is the basic structural unit of various biologically active natural products. Most benzofurans have strong biological activities, such as antifungal, antibacterial, antitumor and antiviral activities, and are increasingly attracting the attention of chemical and pharmaceutical researchers around the world. The structural diversity of benzofuran derivatives is related to the wide range of biological activities of this class of compounds. For example, benzbromarone and amiodarone, which contain benzene ring structural units, are used to treat gouty arthritis and arrhythmias, respectively. Therefore, benzofuran compounds are an important source of drug lead compounds. Recently, we isolated and identified seven benzofuran compounds from a mangrove sediment fungus, Striaticonidium cinctum SCSIO 41432: stribenfuran A(1), stribenfuran B(2), stribenfuran C(3), stribenfuran D(4), stribenfuran E(5), stribenfuran H(6) and stribenfuran I(7). Activity studies found that these compounds had different degrees of inhibitory activity against multiple plant pathogenic fungi and pathogenic bacteria. Summary of the invention:

[0003] The first object of the present invention is to provide a mangrove sediment-derived fungus Striaticonidium cinctum SCSIO 41432 that can produce benzofuran antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7), which was deposited in Guangdong Provincial Microbiological Culture Collection Center (GDMCC) on December 19, 2024, with a deposit number of GDMCC NO.65653.

[0004] The fungus Striaticonidium cinctum SCSIO 41432 of the present invention is isolated from the mangrove bottom mud of the Gaoqiao mangrove forest in Zhanjiang (109.767° east longitude, 21.573° north latitude), and the fungus body is white. The ITS1 and ITS4 sequences of the fungus are amplified by PCR using a conventional method, and the sequences are submitted to GenBank after sequencing to obtain the sequence number PQ460799. The ITS gene sequence analysis results show that the similarity between the strain and Striaticonidium cinctum reaches 98%, and the phylogenetic relationship between the fungus and a group of Streptomyces species is clearly revealed by the neighbor-joining method ( Figure 2 ). Therefore, the bacterium was named Streptomyces Striaticonidiumcinctum SCSIO 41432.

[0005] The second object of the present invention is to provide antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7), the structures of which are shown below:

[0006]

[0007] The third object of the present invention is to provide a method for preparing antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7), which are prepared and separated from the fermentation culture of the Striaticonidium cinctumSCSIO 41432. The method is characterized in that it comprises the following steps:

[0008] a. preparing a fermentation culture of Striaticonidium cinctum SCSIO 41432, soaking the fermentation culture in ethyl acetate, separating mycelium and fermentation liquid with gauze after ultrasonication, and then extracting with ethyl acetate, concentrating and combining to obtain a black crude extract;

[0009] b. The extract was separated by reverse medium pressure C18 column chromatography, with the mobile phase being methanol / water with a volume ratio of 10:90 to 100:0 for gradient elution;

[0010] The eluted portion Fr.6 with a mobile phase of methanol / water = 60:40 was eluted by normal phase medium pressure chromatography, a silica gel separation column, and a mobile phase of dichloromethane / methanol 100:0, 98:2, 95:5, 90:10, 70:30 gradient to obtain five elution portions Frs.6-1-6-5. Fr.6-1 was separated and purified by semi-preparative HPLC to obtain compounds stribenfuran D (4) and stribenfuran B (2);

[0011] The first and second elution parts Fr.9 and Fr.10 with a mobile phase of methanol / water = 80:20 were eluted by normal phase medium pressure chromatography and a silica gel separation column with a mobile phase of dichloromethane / methanol 100:0, 98:2, 95:5, 90:10, 70:30, 40:60, 0:100 v / v gradient to obtain 7 elution parts Frs.9-1-9-7 and Frs.10-1-10-7 respectively; component Fr.9-4 was separated and purified by semi-preparative HPLC to obtain stribenfuran E (5) and stribenfuran I (9); component Fr.9-5 was separated and purified by semi-preparative HPLC to obtain stribenfuran H (8);

[0012] The 2% methanol washout fraction Fr.10-2 of normal phase chromatography was separated and purified by HPLC to obtain stribenfuran C (3). The first elution fraction Fr.13 of reverse phase chromatography with methanol / water = 100:0 was separated and purified by HPLC to obtain stribenfuran A (1).

[0013] Preferably, the fermentation culture of Striaticonidium cinctum SCSIO 41432 prepared in step a) is prepared by the following method: inoculating activated Striaticonidium cinctum SCSIO 41432 into a seed culture medium, culturing at 28°C, 200rpm, for 3 days to obtain a seed solution, inoculating the seed solution into a fermentation culture medium, and culturing at room temperature for 48 days to obtain a fermentation culture, wherein the formulas of the seed culture medium and the fermentation culture medium are both PDB culture medium.

[0014] The fourth object of the present invention is to provide the use of the mangrove fungus Striaticonidium cinctumSCSIO 41432 in the preparation of benzofuran antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7).

[0015] A fifth object of the present invention is to provide the use of the above-mentioned benzofuran antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7) in the preparation of antibacterial drugs.

[0016] Preferably, the antibacterial drug is an antifungal such as apple anthracnose, wheat fusarium rust, wheat sheath blight, corn fusarium rust, yam anthracnose, rubber tree anthracnose, peanut sclerotinia, banana wilt, rice blast, apple black spot, pineapple black heart or mango anthracnose and an antibacterial drug such as Micrococcus luteus, Streptococcus faecalis, Streptococcus suis and Staphylococcus aureus.

[0017] The Striaticonidium cinctum SCSIO 41432 of the present invention can produce benzofuran antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7), and the bacteria can be used to prepare the seven antibiotics, thereby providing a new method for the production and preparation of the seven antibiotics.

[0018] The Striaticonidium cinctum SCSIO 41432 of the present invention was deposited in the Guangdong Microbiological Culture Collection Center (GDMCC) on December 19, 2024, address: 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, Institute of Microbiology, Guangdong Academy of Sciences, Postal Code: 510070, and the deposit number is GDMCC NO: 65653. Description of the drawings:

[0019] Figure 1 The compounds of the present invention include structural formulas of seven antibiotics, namely, stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7).

[0020] Figure 2 It is the species with the closest relationship to Striaticonidium cinctum SCSIO 41432 phylogenetic tree of the present invention and the neighbor-joining method based on ITS sequences.

[0021] Figure 3 This is the single crystal structure of the compound stribenfuran A(1).

[0022] Figure 4 For compounds stribenfuran A(1), stribenfuran B(2), stribenfuran C(3), stribenfuran D(4), stribenfuran E(5), stribenfuran H(6) and stribenfuran I(7) 1 H- 1 Key 2D NMR data of H COSY, HMBC and NOESY.

[0023] Figure 5 Experimental and calculated ECD spectra of compounds stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7). Specific implementation method:

[0024] The following examples are provided to further illustrate the present invention, but are not intended to limit the present invention.

[0025] Example 1 Isolation, purification and identification of Striaticonidium cinctum SCSIO 41432

[0026] The DNA of the fungus Striaticonidium cinctumSCSIO 41432 was extracted using the TSINGKE universal plant DNA extraction kit, and the DNA was amplified by PCR using universal primers ITS1 and ITS4 for fungal species identification. The PCR product was sequenced, and the sequence splicing results are as follows:

[0027] Strain source: The mangrove fungus Striaticonidium cinctum SCSIO 41432 was isolated from the mangrove mud of Gaoqiao mangrove in Zhanjiang (109.767° east longitude, 21.573° north latitude). The fungus is white.

[0028] Identification of strain: After sequencing, it was submitted to NCBI's GenBank and obtained the sequence number PQ460799. The applicant also holds the strain and guarantees that it will be available to the public within 20 years from the date of application. The ITS gene sequence analysis results showed that the strain has a similarity of 98% with Striaticonidium cinctum. The neighbor-joining method clearly revealed the phylogenetic relationship between the strain and a group of Streptomyces species ( Figure 2). Therefore, the bacterium was named Streptomyces cinctumSCSIO 41432, and the bacterium is currently preserved in the Guangdong Provincial Microbial Culture Collection Center.

[0029] Striaticonidium cinctum SCSIO 41432 was deposited on December 19, 2024 in the Guangdong Microbiological Culture Collection Center (GDMCC), address: 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, Institute of Microbiology, Guangdong Academy of Sciences, Postal Code: 510070, China, with the deposit number GDMCC NO: 65653.

[0030] Example 2 Scale fermentation of Striaticonidium cinctum SCSIO 41432

[0031] Seed culture: First, the strain Striaticonidium cinctum SCSIO41432 preserved in paraffin oil was inoculated into MB plates (comprising 1.5% malt extract powder, 1.8% agar powder, 2.5% sea salt, pH 7.4-7.8, by mass fraction) and cultured until new colonies grew, then inoculated into PDB medium (24 g PDB dry powder medium / 1 L), and cultured at 28° C. in a shaking incubator (180 rpm) for 3 days.

[0032] Large-scale fermentation culture: The fermentation medium is the same as the seed medium, both are PDB medium. The seed liquid is inoculated into 300 mL of sterilized PDB medium for fermentation. A total of 130 bottles (40 L) are fermented at room temperature for 48 days to prepare the PDB medium fermentation product of the fungus Striaticonidium cinctum SCSIO 41432.

[0033] Example 3 Isolation of benzofuran antibiotics produced by Striaticonidium cinctum SCSIO 41432

[0034] 1. Extraction of fermentation broth: After the fermentation of PDB medium, the PDB medium fermentation product was obtained, the mycelium was inactivated with an equal volume of ethyl acetate, ultrasonicated for 15 minutes, and then the mycelium and the fermentation broth were separated with gauze, and then extracted with ethyl acetate for 3 times until colorless, and then concentrated by rotary evaporation and combined to obtain a black crude extract (53.6 g).

[0035] 2. Extraction, separation and identification of compounds stribenfuran A(1), stribenfuran B(2), stribenfuran C(3), stribenfuran D(4), stribenfuran E(5), stribenfuran H(6) and stribenfuran I(7)

[0036] The crude extract was dissolved in a small amount of methanol and mixed with silica gel for medium-pressure reverse-phase C18 column chromatography. The mobile phase was methanol / water with a volume ratio of 10:90 (4 column volumes), 20:80 (4 column volumes), 30:70 (4 column volumes), 40:60 (4 column volumes), 50:50 (4 column volumes), 60:40 (4 column volumes), 70:30 (8 column volumes), 80:20 (8 column volumes), 90:10 (8 column volumes), and 100:0 (8 column volumes) for gradient elution. The elution parts of 4 column volumes were combined into one part, and 14 elution parts Fr.1–Fr.14 were obtained in sequence.

[0037] The eluted fraction Fr.6 with the mobile phase of methanol / water = 60:40 was eluted by normal phase medium pressure chromatography, silica gel separation column, and the mobile phase was dichloromethane / methanol 100:0, 98:2, 95:5, 90:10, 70:30 v / v gradient, and five elution fractions Frs.6-1-6-5 were obtained in sequence. Fr.6-1 (dichloromethane / methanol 100:0 elution fraction) was separated and purified using a semi-preparative Hitachi HITACHI high performance liquid chromatography and NanoChrom column (ChromCore C18, 5μm, 10×250mm) (the mobile phase was 50% CH3CN / H2O (0.04% TFA), 3mL / min) to obtain the compound stribenfuran D (4) (6.4mg, t R =10.6min) and stribenfuran B(2)(24.6mg,t R =12.5min).

[0038] The first and second elution fractions Fr.9 and Fr.10, whose mobile phase was methanol / water = 80:20, were eluted by normal phase medium pressure chromatography, silica gel separation column, and the mobile phase was dichloromethane / methanol 100:0, 98:2, 95:5, 90:10, 70:30, 40:60, 0:100 v / v gradient, and 7 elution fractions Frs.9-1-9-7 and Frs.10-1-10-7 were obtained in sequence. Component Fr.9-4 (dichloromethane / methanol 90:10) was separated and purified by semi-preparative Hitachi HITACHI high performance liquid chromatography and NanoChrom column (ChromCore C18, 5μm, 10×250mm) (mobile phase was 80% by volume CH3OH / H2O (0.04% TFA), 3mL / min) to obtain stribenfuran E (5) (3.6mg, t R =25.2min) and stribenfuran I(7)(7.1mg,t R =31.0min). Component Fr.9-5 (dichloromethane / methanol 70:30) was separated and purified by semi-preparative Hitachi HITACHI HPLC and NanoChrom chromatographic column (ChromCore C18, 5μm, 10×250mm) (mobile phase: 50% CH3CN / H2O (0.04% TFA), 2mL / min) to obtain stribenfuran H(6) (3.5mg, t R =29.2min). The 2% methanol washout portion Fr.10-2 was separated and purified using a semi-preparative Hitachi HITACHI HPLC and NanoChrom column (ChromCore C18, 5μm, 10×250mm) (mobile phase: 85% CH3OH / H2O, 3mL / min) to obtain stribenfuran C(3) (9.2mg, t R =19.5min). The first elution fraction Fr.13 of the reversed phase chromatography with methanol / water = 100:0 was separated and purified using a semi-preparative Hitachi HITACHI HPLC and a NanoChrom column (ChromCore C18, 5μm, 10×250mm) (mobile phase: 70% by volume CH3CN / H2O, 3mL / min) to obtain stribenfuran A(1) (145.5mg, t R =13.5min).

[0039] The seven benzofuran compounds prepared from the fermentation culture of the present invention surrounding the mycorrhizal fungus SCSIO 41432 were subjected to structural analysis tests:

[0040] The compound stribenfuran A(1) is a colorless needle-shaped crystal. The negative ion high resolution mass spectrometry HRESIMS shows that its quasi-molecular ion peak is m / z 247.1343[MH] - (The calculated value is C 15 H 19 O3 - ,247.1343), and its molecular formula is estimated to be C 15 H 20 O3, unsaturation is 6. Analysis of compound 1 1 H and HSQC NMR data revealed that the compound has two aromatic hydrogen signals on the 1,2,3,5-tetrasubstituted benzene ring, H-6 (δ H 6.12,s) and H-8(δ H 6.04,s); 2 olefin hydrogen atoms, H-13 (δ H 5.42, overlapped) and H-14 (δ H 5.42, overlapped); 2 methine hydrogen atoms, H-2 (δ H 4.57, p, J = 6.0 Hz) and H-3 (δ H 3.12,m); 3 methylene hydrogen atoms, H2-11(δ H 2.43,t,J=8.0Hz),H2-12(δ H 2.17,m) and H2-16(δ H 3.47,m; 3.76,dd,J=10.0,6.5Hz); two methyl hydrogen atoms, H3-10 (δ H 1.33, dd, J = 6.5, 2.0 Hz) and H3-15 (δ H d, J = 4.0 Hz). In addition to the 11 proton carbon signals mentioned above, there are four non-proton carbon signals (δ C 110.6, C-4; 154.3, C-5; 143.5, C-7; 160.7, C-9) appears 13 C NMR signal. Analysis 1 H- 1HCOSY signals obtained two self-selected systems H3-10 / H-2 / H-3 / H2-16 and H2-11 / H2-12 / H-13 / H-14 / H3-15. The above NMR signals and HMBC related signals H-2 / C-4, C-9; H-3 / C-4, C-5, C-9; H-6 / C-4, C-5, C-8; H-8 / C-4, C-9 indicate that compound 1 has a dihydrobenzofuran skeleton. HMBC related signals H3-10 / C-2, C-3; H2-16 / C-2, C-3, C-4; H2-11 / C-6, C-7, C-8 confirm that the remaining methyl, hydroxymethyl and 3-pentene groups are connected to C-2, C-3 and C-7, respectively. The NOESY correlation signals of H3-10 / H-3 and H-2 / H2-16 indicate that H3-10 and H-3 are located on the same side, while H-2 and H2-16 are located on the opposite sides. 1 The H NMR signals overlapped, and the configuration of the double bond of the side chain could not be determined by the H-13 / H-14 coupling constant. Fortunately, X-ray single crystal analysis of compound 1 not only clarified the above relative configuration, but also determined the (2R, 3R) absolute configuration of 1 (CCDC 2401500).

[0041] Using the same strategy, stribenfurans B-E (2-5) were also confirmed to be novel benzofurans with a dihydrobenzofuran skeleton. Structurally, stribenfuran C (3) is a monochloro-substituted compound with a chlorine atom on the benzene ring.

[0042] Stribenfuran H (6) and stribenfuran I (7) are both yellow oils. High-resolution mass spectrometry HRESIMS data showed that they have the same molecular formula C 16 H 22 SO3, with one sulfur atom and 6 unsaturated units. 1 H and 13 Further analysis of the CNMR data showed that it was very similar to stribenfuran A (1). The only difference between them was that the hydroxyl group in 1 was replaced by methyl sulfoxide in 6. This can be seen by δ H / C 3.16,2.95 / 56.0 (CH2-16) at the methylene signal changes, increased δ H / C The structure of stribenfuran I (7) was confirmed by the presence of 2.58 / 38.5 (CH3-18) methyl signals and HMBC related signals from H3-18 to C-16 in 6. Based on the remaining 1D and 2D NMR data, 6 was confirmed to be stribenfuran H (6). The planar structure of compound stribenfuran I (7) was determined to be identical to that of 6 in the same manner.13 C NMR data showed that there was a slight difference at CH-3, indicating that the two compounds are a pair of diastereomers. Considering the same biosynthetic source and the same NOESY data of H3-10 / H-3 and H-2 / H2-16, their absolute configuration in the furan ring is also (2R, 3S). Finally, the absolute configuration of the sulfoxide group (S=O-17) in 6 and 7 was determined to be 17R and 17S, respectively, using the ECD calculation method. It is worth noting that stribenfuran H (6) and stribenfuran I (7) are the first pair of diastereomer chiral sulfoxides in natural benzofuran derivatives.

[0043] The following are the physicochemical properties of each new compound:

[0044] Stribenfuran A(1): Colorless needle-shaped crystals ( Figure 3 ); UV(CH3OH)λ max (logε)210(4.22),230(3.12),282(2.82)nm; ECD(0.3mg / mL,CH3OH)λ max (Δε)205(+2.06),235(+1.08),281(+0.29)nm; IR(film)ν max 3358,2950,1653,1587,1430,1320,1203,1088,1037,970,822cm -1 ; 1 H and 13 NMR data of C, Table 1 and Table 2; HRESIMS m / z 247.1343 [MH] - (calcd for C 15 H 19 O3 - ,247.1343).

[0045] Single crystal data of Stribenfuran A(1): C 15 H 20 O3, Mr=248.31, crystal size 0.35×0.2×0.04mm 3 ,monoclinic, α=90°, β=95.176(2)°, γ=90°, Z=2, T=104(6)K, space group P21, μ(CuKα)=0668mm -1 ,Dcalc=1.211g / cm 3, 5997 reflections collected, 2602 independent reflections (R int = 0.0241, R sigma = 0.0190). The final R1 values were 0.0307 (I > 2σ(I)). The final wR(F 2 ) values were 0.0856 (I > 2σ(I)). The final R1 values were 0.0310 (all data). The final wR(F 2 ) values were 0.0859 (all data). The goodness of fit on F 2 was 1.077. The flack parameter was 0.11(8)( Figure 1 , CCDC 2401500).

[0046] Stribenfuran B(2): yellow oil; UV(CH3OH) λ max (logε) 210(4.26), 230(3.65), 282(2.99) nm; ECD(0.3 mg / mL, CH3OH) λ max (Δε) 205(+1.77), 219(+1.60), 235(+1.38), 282(+0.37) nm; IR(film) ν max 3367, 2929, 1635, 1593, 1436, 1379, 1215, 1047, 1024, 993, 823 cm -1 ; 1 1H and 13 13C NMR data, Tables 1 and 2; HRESIMS m / z 265.1436 [M + H] + (calcd for C 15 15H 21 10O4 + , 265.1434).

[0047] Stribenfuran C(3): yellow oil; UV(CH3OH) λ max (logε) 210(4.34), 260(3.37), 282(3.26) nm; ECD(0.25 mg / mL, CH3OH) λ max(Δε)208(+3.05),239(+0.72),286(+0.16)nm; IR(film)ν max 3385,2931,2852,1627,1598,1456,1373,1307,1147,1070,1024,999,966cm -1 ; 1 H and 13 NMR data of C, Table 1 and Table 2; HRESIMS m / z 283.1094 [M+H] + (calcd for C 15 H 20 ClO3 + ,283.1095).

[0048] Stribenfuran D(4): yellow oil; UV(CH3OH)λ max (logε)208(4.53),282(3.29)nm; ECD(0.10mg / mL,CH3OH)λ max (Δε)205(+3.43),235(+1.76),282(+0.51)nm; IR(film)ν max 3323,2970,2924,2873,1697,1633,1593,1435,1382,1309,1292,1215,1047,1024,827cm -1 ; 1 H and 13 NMR data of C, Table 1 and Table 2; HRESIMS m / z 279.1231 [M+H] + (calcd for C 15 H 19 O5 + ,279.1227).

[0049] Stribenfuran E(5): yellow oil; UV(CH3OH)λ max (logε)210(4.43),281(3.24)nm; ECD(0.10mg / mL,CH3OH)λ max (Δε)205(+2.30),238(+2.15),281(+0.90)nm; IR(film)ν max3344,2964,2929,2852,1627,1604,1435,1377,1360,1298,1217,1049,968,827cm -1 ; 1 H and 13 NMR data of C, Table 1 and Table 2; HRESIMS m / z 290.1752 [M+H] + (calcd for C 17 H 24 NO3 + ,290.1751).

[0050] Stribenfuran H(6): yellow oil; UV(CH3OH)λ max (logε)210(4.34),282(3.20)nm; ECD(0.30mg / mL,CH3OH)λ max (Δε)210(-7.51),237(+2.19),282(+0.82)nm; IR(film)ν max 3334,2929,2856,1625,1608,1435,1354,1301,1217,1049,1014,827cm -1 ; 1 H and 13 NMR data of C, Table 3; HRESIMS m / z 295.1371 [M+H] + (calcd for C 16 H 23 O3S + ,295.1362).

[0051] Stribenfuran I (7): yellow oil; UV(CH3OH)λ max (logε)210(4.35),282(3.42)nm; ECD(0.30mg / mL,CH3OH)λ max (Δε)214(-1.69),237(+1.23),282(+0.36)nm; IR(film)ν max 3366,2933,2856,1625,1660,1435,1377,1294,1217,1022,825cm -1 ; 1 H and 13 NMR data of C, Table 3; HRESIMS m / z 295.1367 [M+H]+ (calcd for C 16 H 23 O3S + ,295.1362).

[0052] According to the above physical and chemical data analysis, the chemical structures of compounds stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7) are shown in formula (I):

[0053]

[0054] Table 1. Compounds 1-5 l H NMR data (δ H ,J in Hz,in DMSO-d6)

[0055]

[0056] a overlapped signal; b 700and 175MHz. c 500and 125MHz.

[0057] Table 2. Compounds 1-5 13 C NMR data (δ C ,type,in DMSO-d6)

[0058]

[0059]

[0060] a 700and 175MHz. b 500and 125MHz.

[0061] Table 3. Compounds 6 and 7 l H(500MHz) and 13 C NMR (125MHz) data

[0062]

[0063] a overlapped signal

[0064] Example 4 Antibacterial experiment on the benzofuran compounds stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7) of Example 3.

[0065] Twelve crop pathogenic fungi, including Colletottichum gloeosporioides Penz., Gibberella sanbinetti, Ceratobasidium cornigerum, Gibberella zeae, Colletotrichum gloeosporioides, Colletotrichum acutatum, Rhizoctonia solani, Fusarium oxysporum, Pyricularia oryaza, Alternaria alternate, Curvularia australiensis, and Colletotrichum asianum, were used as test fungi. Micrococcus luteus, Enterococcus faecalis, and Streptococcus pyogenes were used as test fungi. faecalis), Streptococcus suis and Staphylococcus aureus were used as indicator bacteria. The antibacterial activity of compounds stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7) was tested in a 200 μL system using the 96-well plate pouring method. The positive control drugs were nystatin and ampicillin. Three parallels were made for each sample. The experimental results are shown in Table 4.

[0066] Table 4. Minimum inhibitory concentrations of compounds against 12 strains of tested fungi (μg / mL)

[0067]

[0068] Results and discussion: Compounds 1-7 showed broad-spectrum and different-intensity inhibitory activities against 12 pathogenic fungi and 4 pathogenic bacteria of crops. Among them, compound 4 had good inhibitory activity against Colletotrichum rubrum, while compounds 6 and 7 had good inhibitory activity against Micrococcus luteus, and their minimum inhibitory concentration values ​​were all 1.6 μg / mL.

Claims

1. Striaticonidium cinctum SCSIO 41432, whose deposit number is: GDMCC NO: 65653.

2. The benzofuran antibiotic stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) or stribenfuran I (7), or a pharmaceutically acceptable salt thereof, the chemical structure of which is shown in formula (I): 1R1=H,R2=H,R3=H,R4=OH 2R1=H,R2=OH,R3=H,R4=OH 3R1=Cl,R2=H,R3=H,R4=OH 4R1=H,R2=H,R3=COOH,R4=OH 5R1=H,R2=H,R3=H,R4=NHCOCH3 6R1=H,R2=H,R3=H,R4=SOCH3,17R 7R1=H,R2=H,R3=H,R4=SOCH3,17S Formula (I).

3. A method for preparing the antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7) according to claim 2, characterized in that: The invention is isolated from the fermentation culture of Striaticonidium cinctum SCSIO 4143 as claimed in claim 1.

4. The preparation method according to claim 3, characterized in that: The following steps are involved: a. preparing a fermentation culture of Striaticonidium cinctum SCSIO 41432, soaking the fermentation culture in ethyl acetate, separating mycelium and fermentation liquid with gauze after ultrasonication, and then extracting with ethyl acetate, concentrating and combining to obtain a black crude extract; b. The extract was separated by reverse medium pressure C18 column chromatography, with the mobile phase being methanol / water with a volume ratio of 10:90 to 100:0 for gradient elution; The eluted portion Fr.6 with a mobile phase of methanol / water = 60:40 was eluted by normal phase medium pressure chromatography, a silica gel separation column, and a mobile phase of dichloromethane / methanol 100:0, 98:2, 95:5, 90:10, 70:30 gradient to obtain five elution portions Frs.6-1-6-5. Fr.6-1 was separated and purified by semi-preparative HPLC to obtain compounds stribenfuran D (4) and stribenfuran B (2); The first and second elution parts Fr.9 and Fr.10 with a mobile phase of methanol / water = 80:20 were eluted by normal phase medium pressure chromatography and a silica gel separation column with a mobile phase of dichloromethane / methanol 100:0, 98:2, 95:5, 90:10, 70:30, 40:60, 0:100 v / v gradient to obtain 7 elution parts Frs.9-1-9-7 and Frs.10-1-10-7 respectively; component Fr.9-4 was separated and purified by semi-preparative HPLC to obtain stribenfuran E (5) and stribenfuran I (9); component Fr.9-5 was separated and purified by semi-preparative HPLC to obtain stribenfuran H (8); The 2% methanol washout fraction Fr.10-2 of normal phase chromatography was separated and purified by HPLC to obtain stribenfuran C (3). The first elution fraction Fr.13 of reverse phase chromatography with methanol / water = 100:0 was separated and purified by HPLC to obtain stribenfuran A (1).

5. The preparation method according to claim 4, characterized in that: The fermentation culture of Striaticonidium cinctum SCSIO 41432 prepared in step a) is prepared by the following method: inoculating activated Striaticonidium cinctum SCSIO 41432 into a seed culture medium, culturing at 28°C, 200rpm for 3 days to obtain a seed solution, inoculating the seed solution into a fermentation culture medium, and culturing at room temperature for 48 days to obtain a fermentation culture, wherein the formulas of the seed culture medium and the fermentation culture medium are both PDB culture medium.

6. Use of the Striaticonidium cinctum SCSIO 41432 of claim 1 in the preparation of the benzofuran antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7) of claim 2.

7. Use of the benzofuran antibiotics stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) and stribenfuran I (7) according to claim 2 in the preparation of antibacterial drugs.

8. The use according to claim 7, characterized in that: The antibacterial drug is an antifungal or antibacterial drug.

9. The use according to claim 8, characterized in that: The antifungal drug is a drug against apple anthracnose, wheat fusarium rust, wheat sheath blight, corn fusarium rust, yam anthracnose, rubber tree anthracnose, peanut sclerotinia, banana wilt, rice blast, apple black spot, pineapple black heart or mango anthracnose; the antibacterial drug is a drug against Micrococcus luteus, Streptococcus faecalis, Streptococcus suis or Staphylococcus aureus.

10. An antibacterial drug, characterized in that: The invention comprises an effective amount of the benzofuran antibiotic stribenfuran A (1), stribenfuran B (2), stribenfuran C (3), stribenfuran D (4), stribenfuran E (5), stribenfuran H (6) or stribenfuran I (7) as claimed in claim 2 as an active ingredient, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

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