CN115724816B - Chromone crystal form in mangrove-derived fungi and preparation and application thereof - Google Patents
Chromone crystal form in mangrove-derived fungi and preparation and application thereof Download PDFInfo
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- CN115724816B CN115724816B CN202210952965.5A CN202210952965A CN115724816B CN 115724816 B CN115724816 B CN 115724816B CN 202210952965 A CN202210952965 A CN 202210952965A CN 115724816 B CN115724816 B CN 115724816B
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- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 241000233866 Fungi Species 0.000 title claims abstract description 17
- 239000013078 crystal Substances 0.000 title claims abstract description 17
- 240000002044 Rhizophora apiculata Species 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 229940125904 compound 1 Drugs 0.000 claims description 10
- 239000003963 antioxidant agent Substances 0.000 claims description 9
- 230000003078 antioxidant effect Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000012669 liquid formulation Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 229910052799 carbon Inorganic materials 0.000 description 38
- 150000001875 compounds Chemical class 0.000 description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 14
- 238000010586 diagram Methods 0.000 description 13
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 229940126214 compound 3 Drugs 0.000 description 8
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 229940125782 compound 2 Drugs 0.000 description 7
- 239000012046 mixed solvent Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- 239000003643 water by type Substances 0.000 description 6
- 239000003480 eluent Substances 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 4
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 3
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 3
- 125000005704 oxymethylene group Chemical group [H]C([H])([*:2])O[*:1] 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- -1 terpenoid compounds Chemical class 0.000 description 3
- 239000012224 working solution Substances 0.000 description 3
- WELXSIFHTDZTJK-UHFFFAOYSA-N 5-hydroxy-2-methylchromen-4-one Chemical compound C1=CC=C2OC(C)=CC(=O)C2=C1O WELXSIFHTDZTJK-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 150000004777 chromones Chemical class 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- VTNULXUEOJMRKZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2H-tetrazol-5-ylmethyl)benzamide Chemical compound N=1NN=NC=1CNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O VTNULXUEOJMRKZ-UHFFFAOYSA-N 0.000 description 1
- DZNDULZELVTJGJ-UHFFFAOYSA-N 5,8-dihydroxy-2-methylchromen-4-one Chemical compound Cc1cc(=O)c2c(O)ccc(O)c2o1 DZNDULZELVTJGJ-UHFFFAOYSA-N 0.000 description 1
- 241000256852 Aculeata Species 0.000 description 1
- RSQWUKMYBGIWCC-GMSGAONNSA-N C1=CC(O)=C2[C@H](OC)C[C@@H](C)OC2=C1 Chemical compound C1=CC(O)=C2[C@H](OC)C[C@@H](C)OC2=C1 RSQWUKMYBGIWCC-GMSGAONNSA-N 0.000 description 1
- 241001134038 Daldinia eschscholtzii Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 230000002292 Radical scavenging effect Effects 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- 150000008375 benzopyrones Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 238000009629 microbiological culture Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a chromone crystal form in mangrove-derived fungi, and preparation and application thereof, wherein the chromone crystal form data are as follows: orthorhombic system, space group P2 1 2 1 2 1 The unit cell parameters are α＝90°,β＝90°,γ＝90°,Z＝4,D x ＝1.381g/cm 3 ,μ(Cu Kα)＝0.89mm ‑1 F (000) = 548,1824 observable points [ I>2σ(I)]The observable point refinement final bias factor r=0.0491, wrs=0.0812, the fly constant is 0.02 (6);
Description
Technical Field
The invention belongs to the field of secondary metabolites of mangrove endophytic fungi, and particularly relates to a chromone crystal form in mangrove-derived fungi, and preparation and application thereof.
Background
The applicant separates and obtains series of mixed terpenoid compounds with insecticidal activity from the endophytic fungi TGM112 of the mangrove aculeata, which is one of important sources of novel and unique compounds with marine endophytic fungi structure; and separating from another endophytic fungus (CN 201910431601.0, CN 201910427992.9) to obtain benzopyrone derivatives. The applicant of the present invention further researches fungus HJ004 (preservation number: CGMCC No. 17774), and discovers a series of new chromone derivatives and other antioxidant active compounds, and obtains a new chromone compound crystal form from the new chromone derivatives and other antioxidant active compounds.
Disclosure of Invention
The invention provides a chromone crystal form in mangrove-derived fungi, which is characterized in that the chromone structure is shown as a compound 1, and the crystal data are as follows: orthorhombic system, space group P2 1 2 1 2 1 The unit cell parameters are α＝90°,β＝90°,γ＝90°,/>Z＝4,D x ＝1.381g/cm 3 ,μ(Cu Kα)＝0.89mm -1 F (000) = 548,1824 observable points [ I>2ζ(I)]The observable point refinement final bias factor r=0.0491, wrs=0.0812, the fly constant is 0.02 (6);
another embodiment of the present invention provides the use of mangrove-derived fungus HJ004 in the preparation of the above-described chromone crystalline form. Accession number of mangrove-derived fungus HJ 004: CGMCC No.17674.
Another embodiment of the present invention provides a method for preparing the chromone crystal form, which is characterized by comprising the following steps:
and (3) dissolving the compound 1 in a solvent, and naturally crystallizing to obtain the chromone crystal form.
Another embodiment of the present invention provides the use of the above-described chromone crystalline form or a pharmaceutically acceptable salt thereof in the preparation of an antioxidant.
A pharmaceutical composition characterized in that the pharmaceutical composition comprises the chromone crystal form or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition may also include other antioxidants. The pharmaceutical composition may also include pharmaceutically acceptable excipients. The dosage form of the pharmaceutical composition is preferably a solid preparation or a liquid preparation, etc.
The term "pharmaceutically acceptable salts" in the present invention refers to non-toxic addition salts of inorganic or organic acids and/or bases, see "Salt selection for basic drugs", int.j.pharm. (1986), 33,201-217.
The invention relates to strain preservation information of mangrove-derived fungi HJ 004: preservation unit name: china general microbiological culture Collection center (China Committee for culture Collection); deposit unit address: the institute of microbiology, national academy of sciences, north chen xi lu 1, 3, the region of the morning sun in beijing; preservation date: 24 days of 2019, 4 months; preservation number: CGMCC No.17674; classification naming: daldinia eschscholtzii. In chinese patent application No.: CN201910431601.0 and CN201910427992.9 are explicitly described.
It is understood that the above-described technical features of the present invention and the technical features specifically described below (e.g., in the examples) may be combined with each other within the scope of the present invention, thereby constituting new or preferred technical solutions. And are limited to a space, and are not described in detail herein.
Drawings
FIG. 1 is a schematic diagram of Compounds 1-3 1 H- 1 H COSY and HMBC correlation diagrams;
FIG. 2 is an X-ray diagram of Compound 1;
FIG. 3 is a NOE correlation diagram for Compound 3;
FIG. 4a is an ECD plot of Compound 2, and FIG. 4b is a CD plot of Compound 3;
FIG. 5 is a diagram of Compound 1 1 H NMR chart;
FIG. 6 is a diagram of Compound 1 13 C NMR chart;
FIG. 7 is a DEPT-135 diagram of Compound 1;
FIG. 8 is a HSQC pattern for Compound 1;
FIG. 9 is a diagram of Compound 2 1 H NMR chart;
FIG. 10 is a diagram of Compound 2 13 C NMR chart;
FIG. 11 is a DEPT-135 diagram of Compound 2;
FIG. 12 is the HSQC pattern of Compound 2;
FIG. 13 is a diagram of Compound 3 1 H NMR chart;
FIG. 14 is a diagram of Compound 3 13 C NMR chart;
FIG. 15 is a DEPT-135 diagram of compound 3;
FIG. 16 is the HSQC pattern of Compound 3.
Detailed Description
The examples provided below are presented in more detail to facilitate a further understanding of the present invention. These examples are provided only for better understanding of the present invention and are not intended to limit the scope or practice of the present invention, and the embodiments of the present invention are not limited to the following.
Example 1
(1) Preparing a fermentation medium: the formulation was added to 3g sea salt, 3g glucose, 100mL distilled water and 100g rice per Erlenmeyer flask (1L). And (5) extinguishing at 120 ℃ for 25-30 minutes. And co-fermenting 60 bottles.
Inoculating mangrove source fungus HJ004 into a fermentation medium, and standing and culturing at 26-28 ℃ for 30 days to obtain a fermented product;
(2) Extracting the fermented product obtained in the step (1) with equal volume of ethyl acetate for 3 times, combining ethyl acetate phases, and concentrating under reduced pressure to obtain 67g of extract;
(3) Performing gradient elution on the extract obtained in the step (2) by using petroleum ether-ethyl acetate as an eluent, wherein the elution gradients are respectively 100:0, 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, 10:90 and 0:100, two column volumes are collected by each gradient, and the two column volumes are divided into 7 components according to the polarity, wherein the component 1 is eluted by the gradient 100:0-90:10, the component 2 is eluted by the gradient 80:20-70:30, the component 3 is eluted by the gradient 60:40, the component 4 is eluted by the gradient 50:50, the component 5 is eluted by the gradient 40:60-30:70, the component 6 is eluted by the gradient 20:80-10:90, and the component 7 is eluted by the gradient 0:100; wherein the component 2 is subjected to normal phase silica gel column chromatography, and the eluent is petroleum ether: eluting 4-5 column volumes by using a mixed solvent of ethyl acetate=9:1-7:3, concentrating under reduced pressure, and then performing Sephadex LH-20 gel column chromatography, wherein the eluent is CHCl 3 The mixed solvent of MeOH=1:1, eluting for 4-5 column volumes, concentrating under reduced pressure, and preparing by high performance liquid chromatography HPLC, wherein the chromatographic column is Waters C18, 9.4X105 mm,7 μm, the flow rate is 2mL/min, and the mobile phase is MeOH: H 2 O=73:27, giving compound 5 (6.0 mg); wherein the component 3 is subjected to normal phase silica gel column chromatography, and the eluent is petroleum ether: eluting 4-5 column volumes of the mixed solvent of ethyl acetate=9:1-1:3, and dividing the mixed solvent into four components of 3a-3d according to the polarity size, wherein the component 3b is prepared by High Performance Liquid Chromatography (HPLC), the chromatographic column is Waters C18, 9.4x250 mm,7 μm, the flow rate is 2mL/min, and the mobile phase is MeOH: H 2 O=45:55, yielding compound 4 (4.0 mg) and compound 6 (3.0 mg); the method comprises the steps of carrying out a first treatment on the surface of the The 3C component is prepared by high performance liquid chromatography HPLC, the chromatographic column is Waters C18, 9.4X105 mm,7 μm, the flow rate is 2mL/min, and the mobile phase is MeOH: H 2 O=40:60, yielding compound 3 (15.0 mg) and compound 9 (36.0 mg); the 3d component is prepared by high performance liquid chromatography HPLC, the chromatographic column is Waters C18, 9.4X105 mm,7 μm, the flow rate is 2mL/min, and the mobile phase is MeOH: H 2 O=45:55, yielding compound 10 (6.0 mg) and compound 11 (21.0 mg); wherein the component 4 is eluted by normal phase silica gel column chromatographyThe agent is petroleum ether: eluting 4-5 column volumes of the mixed solvent of ethyl acetate=9:1-0:1, and dividing the mixed solvent into four components of 4a-4d according to the polarity size, wherein the component 4b is prepared by High Performance Liquid Chromatography (HPLC), the chromatographic column is Waters C18, 9.4x250 mm,7 mu m, the flow rate is 2mL/min, and the mobile phase is MeOH: H 2 O=35:65, yielding compound 1 (15.0 mg) and compound 2 (9.0 mg); the 4C component is prepared by high performance liquid chromatography HPLC, the chromatographic column is Waters C18, 9.4X105 mm,7 μm, the flow rate is 2mL/min, and the mobile phase is MeOH: H 2 O=30:70, giving compound 7 (15.0 mg) and compound 8 (12.0 mg). The eluent or the mobile phase is in a volume ratio.
The NMR, MS and other structure corroboration data of the compounds 4-11 are consistent with the known report, and the structure corroboration data of the compounds 1-11 are as follows:
compound 1: UV (MeOH) lambda max (logε)230(1.18)270(0.20)304(0.58)nm；IR(KBr)ν max 3562,3250,2982,1685,1625cm -1 ； 1 H and 13 C NMR is shown in Table 1; HRESIMS m/z 263.0911[ M+H ]] + (calcd for C 14 H 15 O 5 ,263.0914).
Compound 2: [ alpha ]] 25 D +3.4(c 0.2,MeOH)；UV(MeOH)λ max (logε)216(1.63)249(1.26)280(0.38)288(0.39)nm；ECD(c 0.2,MeOH)λ max (Δε)219(-3.1)260(1.1)nm；IR(KBr)ν max 3550,3017,2981,1638,1617cm -1 ； 1 H and 13 C NMR is shown in Table 1; HRESIMS m/z 205.0867[ M-H ]] - (calcd for C 12 H 13 O 3 ,205.0870).
Compound 3: [ alpha ]] 25 D -38.5(c 0.2,MeOH)；UV(MeOH)λ max (logε)223(2.69)nm；ECD(c 0.2,MeOH)λ max (Δε)218(+30.2),243(-8.4)nm；IR(KBr)ν max 3549,3473,3414,3020,2980,1717,1460cm -1 ； 1 H and 13 C NMR is shown in Table 1; HRESIMS m-z 221.1144[M+Na] + (calcd for C 11 H 18 O 3 Na,221.1148).
Compound 4 is a colorless oil, ESIMS m/z 229.1[ M+Na ]] + It is estimated that the molecular weight is 206.1 and the molecular formula is C 11 H 10 O 4 . At the position of 1 The H NMR spectrum gives an intramolecular hydrogen bond signal delta H 11.94 (s) two aromatic Hydrogen signals delta H 7.14 (d, j=8.8 Hz) and δ H 6.71 (d, j=8.8 Hz), an alkene hydrogen signal δ H 6.13 (s) a methyl-oxygen signal delta H 3.91 (s), a methyl signal delta H 2.44 (s). At the position of 13 The C NMR spectrum gave 11 carbon signals, including a carbonyl carbon signal delta C 183.5, six aromatic carbon signals delta C 167.7,153.7,146.5,140.2,118.5,111.2 two olefinic carbon signals delta C 109.9,109.6, a methyl carbon signal delta C 57.3, a methyl carbon signal delta C 20.8, compound 4 is 5-hydroxy-8-methoxy-2-methyhreomon (Rao, c.r.; venkateswarlu, v.recl. Trav.chim. Pay. B.1956,75,1321.).
Compound 5 is a colorless oil, ESIMS m/z 199.0[ M+Na ]] + It is estimated that the molecular weight is 176.0 and the molecular formula is C 10 H 8 O 3 . At the position of 1 The H NMR spectrum gives an intramolecular hydrogen bond signal delta H 12.52 (s) three aromatic Hydrogen signals delta H 7.47(t,J＝8.4Hz),δ H 6.82 (t, j=8.4 Hz) and δ H 6.75 (t, j=8.4 Hz), an alkene hydrogen signal δ H 6.10 (s), a methyl signal delta H 2.37 (s). At the position of 13 The C NMR spectrum gave 10 carbon signals, including a carbonyl carbon signal delta C 183.6, six aromatic carbon signals delta C 167.8,160.9,156.9,135.2,111.3,110.5 two olefinic carbon signals delta C 109.2,106.9, a methyl carbon signal delta C 20.7, compound 5 was identified as 5-hydroxy-2-methyl-4H-chromen-4-one (Dai, J.Q.; krohn, K.; floerke, U.; draeger, S.; schulz, B.; kiss-Szikszai, A.; antus, S.; kurtan, T.; van Ree, T.Eur.J. Org. chem.2006,15,3498.).
Compound 6 is a colorless oil, ESIMS m/z 195.2[ M ]H] + It is estimated that the molecular weight is 194.2 and the molecular formula is C 11 H 14 O 3 . At the position of 1 Three aromatic hydrogen signals delta are given in the H NMR spectrum H 7.15(t,J＝8.4Hz),δ H 6.53 (d, j=8.4 Hz) and 7.25 (t, j=8.0 Hz), two oxymethylene signals δ H 4.95 (dd, j=4.4, 2.0 hz) and 4.24 (m), a methyl-oxygen signal δ H 3.87 (s), a methylene group delta H [2.06(m),1.69(m)]A methyl signal delta H 1.43 (d, j=6.4 Hz). At the position of 13 The C NMR spectrum gave 11 carbon signals, including six aromatic carbon signals delta C 158.7,156.0,129.5,113.4,110.2,101.9 two oxygen-methyl-carbon signals delta C 67.9,59.6, a methyl carbon signal delta C 55.7, a methylene carbon signal delta C 37.0, a methyl carbon signal delta C Compound 6 was identified as (2 r,4 r) -3,4-dihydro-5-methoxy-2-methyl-2H-1-benzopyran-4-ol (Yang, w.c.; chen, y.; cai, r.l.; zou, g.; wang, b.; she, z.g. chem. Biodivers.2020,17, e 2000192). Compound 7 is a colorless oil, ESIMS m/z 243.1[ M+Na ]] + It is estimated that the molecular weight is 220.1 and the molecular formula is C 12 H 12 O 4 . At the position of 1 The H NMR spectrum gives an intramolecular hydrogen bond signal delta H 12.82 (s) two aromatic Hydrogen signals delta H 6.32 (d, j=1.6 Hz) and δ H 6.16 (d, j=1.6 Hz), an alkene hydrogen signal δ H 6.14 (s) two methylene signals delta H 2.57 (t, j=7.6 Hz) and δ H 1.66 (m), a methyl signal delta H 0.93 (t, j=7.6 Hz). At the position of 13 The C NMR spectrum gave 12 carbon signals, including a carbonyl carbon signal delta C 181.8, six aromatic carbon signals delta C 164.3,161.5,157.8,103.5,98.8,93.8 two olefinic carbon signals delta C 170.4,107.4 two methylene carbon signals delta C 35.0,19.4, a methyl carbon signal delta C Compound 7 was identified as 5, 7-dihydroxy-2-proplylchrone (Kato, h.; li, w.; koike, m.; wang, y.h.; koike, k.phytochemistry.2010,71,1925.).
Compound 8 is a colorless oil, ESIMS m/z 193.1[ M+H ]] + It is estimated that the molecular weight is 192.0, molecular formula C 10 H 8 O 4 。 1 H NMR spectrum gives two aromatic hydrogen signals delta H 6.84 (d, j=8.4 Hz) and 6.75 (d, j=8.0 Hz), one olefinic hydrogen signal δ H 6.34 (s), a methyl signal delta H 2.29 (s). At the position of 13 The C NMR spectrum gave 10 carbon signals, including a carbonyl carbon signal delta C 182.1, six aromatic carbon signals delta C 151.9,149.3,133.5,125.2,115.0,111.8 two olefinic carbon signals delta C 164.9,110.8, a methyl carbon signal delta C 19.8, compound 8 was identified as 5,8-dihydroxy-2-methyl-4H-1-benzopyran-4-one (Rao, C.R.; venkateswarlu, V.Recl. Trav. Chim. Pay. B.1956,75,1321.).
Compound 9 is white needle-like crystals, ESIMS m/z 213.2[ M+H ]] + It is estimated that the molecular weight is 212.2 and the molecular formula is C 12 H 20 O 3 。 1 H NMR spectrum gives an olefine hydrogen signal delta H 5.46 (q, j=12.4, 6.4 hz), five methyl signals δ H 0.80 (d, j=6.8 Hz), 1.21(s), 1.18(s), 1.52(s) and 1.54 (d, j=6.8 Hz), three methine signals δ H 2.16 (m), 3.43 (d, J=1.2 Hz) and 4.60 (d, J=11.2 Hz), 13 the C NMR spectrum gave 12 carbon signals, including an ester carbonyl signal delta C 178.3, two olefinic carbon signals delta C 126.3 and 131.6, five methyl carbon signals delta C 10.2,13.1,13.6,22.6,26.4, three methine carbon signals delta C 31.1,76.4,88.1, a quaternary carbon signal delta C 44.0. By calculation of coupling constant, J H3-H4 ＝1.2Hz,J H4-H5 The relative configuration of compound was determined, compound 9 was determined to be heliccolide a (Poch, g.k.; gloer, j.b.j.nat.prod.1989,52,257.).
Compound 10 is a colorless oil, ESIMS m/z 229.2[ M+H ]] + It is estimated that the molecular weight is 228.2 and the molecular formula is C 12 H 20 O 4 . At the position of 1 An olefinic hydrogen signal delta is given in the H NMR spectrum H 5.63 (t, j=6.0 Hz), two oxymethylene signals δ H 4.68(d,J＝10.8Hz),δ H 3.49 (s) a oxymethylene signal delta H 4.18 (m), a methine signal delta H 2.25 (dd, j=13.1, 6.5 hz), three methyl signals δ H 1.63(s),δ H 1.30(s),δ H 1.27 (s) and delta H 0.90 (d, j=10.8 Hz). At the position of 13 The C NMR spectrum gave 12 carbon signals, including a carbonyl carbon signal delta C 180.0, two olefinic carbon signals delta C 133.1,131.1 two oxygen-methyl-carbon signals delta C 87.5,76.9, a methyl-oxygen-methylene-carbon signal delta C 58.9, a quaternary carbon signal delta C 44.3, four methyl carbon signals delta C 26.6,22.8,13.8,11.0 Compound 10 was identified as heliccolide D (Liao, H.X.; zheng, C.J.; huang, G.L.; mei, R.Q.; nong, X.H.; shao T.M.; chen, G.Y.; wang, C.Y.J.Nat.Prod.2019,82,2211.).
Compound 11 is colorless needle-like crystals, ESIMS m/z 271.1[ M+H ]] + It is estimated that the molecular weight is 270.1 and the molecular formula is C 14 H 22 O 5 。 1 The H NMR spectrum gave an olefinic carbon signal delta H 5.58 (t, j=6.8 Hz), three methine signals δ H 2.24 (m), 3.51(s) and 4.71 (d, j=11.2 Hz), a methylene signal δ H 4.68 (m) and five methyl signals delta H 0.90 (d, j=6.8 Hz), 1.27(s), 1.31(s), 1.69(s) and 2.02(s). 13 The C NMR spectrum gave 14 carbon signals, including two carbonyl carbon signals delta C 177.3 and 171.1, two olefinic carbon signals delta C 136.4 and 125.4, a quaternary carbon signal delta C 44.3,3 methine carbon signals delta C 86.8,77.0 and 31.2, a methylene carbon signal delta C 60.6 and five methyl carbon signals delta C 26.5,22.7,20.9,13.8 and 11.2, compound 11 was identified as heliccolide E (Liao, h.x.; zheng, c.j.; huang, g.l.; mei, r.q.; non, x.h.; shao t.m.; chen, g.y.; wang, c.y.j.nat. Prod.2019,82,2211.).
TABLE 1 Compounds 1-3 1 H NMR (400 MHz) and 13 C NMR(100MHz)
example 2
Dissolving compound 1 (2.0 mg) in 5mL of mixed solvent of dichloromethane-methanol (volume ratio of 4:1), standing at room temperature for 48 hr, naturally precipitating crystal, and using HyPix diffractometer (Rigaku XtaLAB Synergy R, hyPix diffractometer X) with Cu K alpha rayDiffraction data were collected by scanning at 120.02 (10) K. The measured crystal size was 0.14X0.13X0.12 mm.
The data for form 1 of compound are: orthorhombic system, space group P2 1 2 1 2 1 The unit cell parameters are α＝90°,β＝90°,γ＝90°,/> Z＝4,D x ＝1.381g/cm 3 ,μ(Cu Kα)＝0.89mm -1 F (000) = 548,1824 observable points [ I>2ζ(I)]The final bias factor r=0.0491, wrs=0.0812, and the fly constant is 0.02 (6) for observable point refinement.
Example 3 antioxidant Activity test
Compounds 1 to 11 were tested for antioxidant activity and the antioxidant capacity of compounds 1 to 11 was evaluated by ABTS radical scavenging method. ABTS mother liquor was prepared with equal volumes of ABTS solution and oxidizer solution. The ABTS working solution was stored at room temperature for 12-16 hours, and then diluted with PBS buffer such that the absorbance of the diluted ABTS working solution minus the corresponding PBS blank was about 0.7 at 734 nm. 200. Mu.L of ABTS diluted working solution and 10. Mu.L of sample are added to each detection 4 well, gently mixed, incubated at room temperature for 2-6 minutes, and then absorbance at 734nm is measured by a full-wavelength multifunctional microplate reader.PBS buffer served as a blank control and trolox served as a positive control. The antioxidant capacity of each sample was calculated as antioxidant capacity = [ (a) Blank group -A Compounds of formula (I) )/A Blank group ]X 100%. Finally, calculating IC using SPSS software 50 Values. The results indicate that the IC of the test compound 50 The values are in the range of 5.57-195.03. Mu.M, all stronger than the positive control trolox (IC) 50 Values 292.12. Mu.M). Wherein the specific values of compounds 1, 5,7, 8 are as follows:
Claims (8)
1. a crystalline form of chromone in mangrove-derived fungi, characterized in that the chromone structure is as shown in compound 1, and the crystal data is as follows: orthorhombic system, space group P2 1 2 1 2 1 The unit cell parameters are α＝90°,β＝90°,γ＝90°,/>Z＝4,D x ＝1.381g/cm 3 ,μ(Cu Kα)＝0.89mm -1 F (000) = 548,1824 observable points [ I>2σ(I)]The observable point refinement final bias factor r=0.0491, wrs=0.0812, the fly constant is 0.02 (6); />
2. Use of mangrove-derived fungus HJ004 for the preparation of the chromone crystalline form of claim 1; accession number of mangrove-derived fungus HJ 004: CGMCC No.17674.
3. A process for preparing the chromone crystalline form of claim 1, comprising the steps of: and (3) dissolving the compound 1 in a solvent, and naturally crystallizing to obtain the chromone crystal form.
4. Use of the chromone crystalline form of claim 1 or a pharmaceutically acceptable salt thereof in the preparation of an antioxidant.
5. A pharmaceutical composition comprising the chromone crystalline form of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
6. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition further comprises other antioxidants.
7. The pharmaceutical composition according to any one of claims 5-6, wherein the pharmaceutical composition further comprises pharmaceutically acceptable excipients.
8. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition is in the form of a solid formulation or a liquid formulation.
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| 1株红树来源真菌Daldinia eschscholtzii HJ001的活性次级代谢产物研究;梅荣清;李灿;王斌;黄国雷;易继凌;陈光英;郑彩娟;;中国海洋药物(06);全文 * |
| 梅荣清 ; 李灿 ; 王斌 ; 黄国雷 ; 易继凌 ; 陈光英 ; 郑彩娟 ; .1株红树来源真菌Daldinia eschscholtzii HJ001的活性次级代谢产物研究.中国海洋药物.2019,(06),全文. * |
| 王东梅 ; 周敏 ; 刘燕 ; 戚华溢 ; 张国林 ; 罗应刚 ; .聚花野丁香的化学成分及其抗氧化活性.应用与环境生物学报.(06),全文. * |
| 聚花野丁香的化学成分及其抗氧化活性;王东梅;周敏;刘燕;戚华溢;张国林;罗应刚;;应用与环境生物学报(06);全文 * |
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