CN116789721B - Application of farnesane sesquiterpenoids in preventing trichinosis - Google Patents
Application of farnesane sesquiterpenoids in preventing trichinosis Download PDFInfo
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- CN116789721B CN116789721B CN202211301331.XA CN202211301331A CN116789721B CN 116789721 B CN116789721 B CN 116789721B CN 202211301331 A CN202211301331 A CN 202211301331A CN 116789721 B CN116789721 B CN 116789721B
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- 206010044608 Trichiniasis Diseases 0.000 title claims abstract description 14
- 208000003982 trichinellosis Diseases 0.000 title claims abstract description 14
- 201000007588 trichinosis Diseases 0.000 title claims abstract description 14
- 150000004346 farnesane derivatives Chemical class 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 36
- -1 farnesane sesquiterpene compound Chemical class 0.000 abstract description 8
- 239000004480 active ingredient Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 2
- 230000001165 anti-coccidial effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 17
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- 241000196324 Embryophyta Species 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
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- 238000010992 reflux Methods 0.000 description 4
- WSNKEJIFARPOSQ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 WSNKEJIFARPOSQ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
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- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
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- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 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 2
- 238000007911 parenteral administration Methods 0.000 description 2
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- 241000722941 Achillea Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000208223 Anacardiaceae Species 0.000 description 1
- 241000208173 Apiaceae Species 0.000 description 1
- 235000003826 Artemisia Nutrition 0.000 description 1
- 235000015758 Artemisia lavandulifolia Nutrition 0.000 description 1
- 241001168876 Artemisia lavandulifolia Species 0.000 description 1
- 235000003261 Artemisia vulgaris Nutrition 0.000 description 1
- 241000208838 Asteraceae Species 0.000 description 1
- 235000004936 Bromus mango Nutrition 0.000 description 1
- 241001611826 Chiliadenus lopadusanus Species 0.000 description 1
- 241000510609 Ferula Species 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241000801118 Lepidium Species 0.000 description 1
- 241001093152 Mangifera Species 0.000 description 1
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- 241000699666 Mus <mouse, genus> Species 0.000 description 1
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- 235000004789 Rosa xanthina Nutrition 0.000 description 1
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- 235000009184 Spondias indica Nutrition 0.000 description 1
- 241001439624 Trichina Species 0.000 description 1
- 229930000062 acyclic sesquiterpene Natural products 0.000 description 1
- 150000000553 acyclic sesquiterpene derivatives Chemical class 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
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- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
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- 238000001514 detection method Methods 0.000 description 1
- 150000004826 dibenzofurans Chemical class 0.000 description 1
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- 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 1
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to application of farnesane sesquiterpenoids in preparation of anti-trichinosis products, and belongs to the field of traditional Chinese medicine and natural medicine pharmacy. The invention relates to an anticoccidial drug taking farnesane sesquiterpene compound as an active ingredient. The invention expands the medicinal value of the farnesane sesquiterpene compound.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicine and natural medicine pharmacy, and particularly relates to a pharmaceutical composition taking farnesane sesquiterpenoids as active ingredients and application thereof in preparation of trichinosis resisting preparations.
Technical Field
The acyclic sesquiterpene is mainly distributed in Compositae of Artemisia, inulae, achillea, scrophulariaceae of rehmanniae radix, and Anacardiaceae of mango, the plant of genus Ferula of Umbelliferae, genus Lepidium of Sapindaceae, etc. has a main type of farnesane sesquiterpenoids (FARNESANE SESQUITERPENOIDS). The literature reports that farnesane sesquiterpenoids have biological activities （Masi M, Roscetto E, Cimmino A, et al. Farnesane-type sesquiterpenoids with antibiotic activity from Chiliadenus lopadusanus. Antibiotics, 2021, 10, 148; Shen C, Huang XY, Geng CA, et al. Artemlavanins A and B from Artemisia lavandulaefolia and their cytotoxicity against hepatic stellate cell line LX2. Nat. Prod. Bioprospect, 2020, 10, 243-250）. such as anticancer, antibacterial and the like, and the activity of the compounds against trichinosis is not reported so far.
Disclosure of Invention
The invention aims to provide a farnesane sesquiterpene compound, a pharmaceutical composition taking the farnesane sesquiterpene compound as an active ingredient, a preparation method of the farnesane sesquiterpene compound and application of the farnesane sesquiterpene compound and the pharmaceutical composition in preparation of an anti-trichinosis preparation.
The above object of the present invention is achieved by the following technical solutions:
Dibenzofuran compounds 1-10 shown in the following structure,
。
The preparation method of the compound 1-10 comprises taking whole plant of Rubus genus plant of Rosaceae family, directly cold soaking with organic solvent chloroform or ethyl acetate or acetone or methanol or ethanol or water or hot reflux extracting, or extracting with above organic solvent or water-cooling or reflux extracting, extracting with ethyl acetate to obtain total extract, and subjecting the total extract to repeated column chromatography to obtain the compound 1-10.
The preparation method of the compounds 1-10 is more specifically as follows:
A: extracting whole plant of Rubus plants with acetone, methanol, ethanol, water-cooled or hot reflux to obtain total extract, extracting with ethyl acetate to obtain ethyl acetate extract, and repeatedly performing column chromatography to obtain compounds 1-10.
B: extracting coarse powder of whole plant of Rubus plant with organic solvent (such as chloroform, methanol, ethanol, acetone, and dichloromethane) directly by cold soaking or hot reflux to obtain total extract, and subjecting the total extract to repeated column chromatography to obtain compounds 1-10.
More specifically, the preparation method of the compound 1-10 comprises the steps of drying the whole plant of the Rubus plant in the shade, crushing the whole plant to 30 meshes, leaching the whole plant with 95% ethanol for 3 times at room temperature, merging the extracting solutions, concentrating the extracting solution under reduced pressure to obtain an extract, suspending the extract with a proper amount of water, distributing the extract with ethyl acetate for several times to obtain an ethyl acetate extract, dissolving the extract with a proper amount of chloroform/acetone, mixing the extract with a silica gel 80-100 meshes, then carrying out column chromatography with 200-300 meshes of silica gel for sectioning and rough separation, carrying out gradient elution with 1:0-0:1 chloroform/acetone or 1:0-0:1 chloroform/methanol to obtain 8 main parts, carrying out silica gel column chromatography with 1:0 chlorine/propane part, 9:1 chlorine/propane part, 8:2 chlorine/propane part and 7:3 chlorine/propane part, carrying out gradient elution with 30:1:2 petroleum ether/acetone to obtain 10 parts, and carrying out repeated gradient elution with 1:0 chloroform/acetone, sepl-18, MCX and MCPh-20, thereby obtaining the compound 1-20.
An anti-trichinosis preparation contains any one of compounds 1-10 and conventional adjuvants.
A pharmaceutical composition comprising a therapeutically effective amount of any one of compounds 1-10 and a pharmaceutically acceptable carrier.
The application of any one of the compounds 1-10 in preparing the preparation for resisting trichinosis.
The application of any compound in preparing medicines for treating trichinosis is provided.
The invention relates to a pharmaceutical composition for resisting trichinosis, which comprises any one of compounds 1-10 and a pharmaceutically acceptable carrier.
The pharmaceutically acceptable carrier in the pharmaceutical composition of the invention refers to a conventional pharmaceutical carrier in the pharmaceutical field. The compounds of the present invention may be administered to a patient in need of such treatment in the form of a composition by oral, nasal inhalation, rectal or parenteral administration. For oral administration, it can be formulated into conventional solid preparations such as tablet, powder, granule, capsule, etc., and liquid preparations such as oil suspension, syrup, elixir, etc.; for parenteral administration, it can be formulated into injectable solutions, etc. Preferred forms are tablets, capsules and injections.
The various dosage forms of the pharmaceutical composition of the present invention can be prepared according to conventional production methods in the pharmaceutical field. For example by mixing the active ingredient with one or more carriers and then forming it into the desired dosage form.
The pharmaceutical composition of the present invention preferably contains 0.1 to 99.5% by weight of active ingredient, most preferably 0.5 to 95% by weight of active ingredient.
The amount of the compound of the present invention to be administered may vary depending on the route of administration, age, weight of the patient, type and severity of the disease to be treated, etc., and the daily dose thereof may be 0.01 to 10 mg/kg body weight, preferably 0.1 to 5 mg/kg body weight. Can be administered one or more times.
The compounds of the invention show better anti-trichinosis activity.
The invention screens the anti-trichina activity of the compounds 1-10, and the compounds show better anti-trichina activity. In trichinosis-resistant applications, compounds 1-10 are applied to a substrate or a population in an amount in the range of 1-1000 μm, preferably 10-200 μm, optionally in combination with a carrier and/or medium.
Detailed Description
The following examples of the invention are intended to further illustrate the nature of the invention so that it may be more fully understood by those skilled in the art, but are not intended to limit the invention in any way.
Example 1:
Extraction, separation and purification of the compounds 1-10 of the present invention:
Drying branches and leaves (15 kg) of Rubus coreanus, pulverizing to 30 mesh, extracting with 95% ethanol at room temperature for 3 times, 60: 60L and 24: 24 h each time, mixing the extractive solutions, and concentrating under reduced pressure to obtain extract (2.7: 2.7 kg). The extract is dissolved by chloroform/acetone, then is adsorbed by a proper amount of 80-100 meshes of silica gel, then is subjected to column chromatography with 3.0 kg of 200-300 meshes of silica gel for sectioning and rough separation, is subjected to gradient elution by chloroform/acetone (1:0-0:1) to obtain 8 main parts, and is subjected to column chromatography by 1:0 chloroform part, 9:1 chlorine/propyl part, 8:2 chlorine/propyl part and 7:3 chlorine/propyl part. Wherein the first elution and the second elution are repeatedly performed with silica gel, RP-18 and Sephadex LH-20 column chromatography to obtain the compound 8-10. And repeatedly performing silica gel, RP-18, MCI and Sephadex LH-20 column chromatography on the third elution part and the fourth elution part to obtain the compounds 1-7.
Example 2:
physical and spectroscopic data for compounds 1-10 of the invention:
Compound 1: colorless oil .UV (MeOH) λmax (log ε): 203 (3.5) nm; CD (MeOH) λmax(Dε): 191 (+3.6), 218 (-0.5) nm; 1H NMR (400 MHz, CD3COCD3) δ: 5.94 (1H, dd, J = 17.3, 10.7 Hz, H-2), 5.67 (1H, dt, J = 15.5, 7.4 Hz, H-5), 5.51 (1H, dt, J = 15.5, 1.2 Hz, H-6), 5.20 (1H, dd, J = 17.3, 1.8 Hz, H-1a), 4.96 (1H, dd, J = 10.7, 1.8 Hz, H-1b), 4.58 (1H, d, J = 7.7 Hz, H-1'), 3.90 (1H, t, J = 6.8 Hz, H-10), 3.80 (1H, dd, J = 11.4, 2.1 Hz, H-6'a), 3.61 (1H, dd, J = 11.4, 4.4 Hz, H-6'b), 3.39 (1H, t, J = 8.7 Hz, H-3'), 3.31 (1H, overlap, H-4'), 3.29 (1H, m, H-5'), 3.11 (1H, dd, J = 8.7, 7.8 Hz, H-2'), 2.21 (2H, dt, J = 7.4, 1.4 Hz, H-4), 1.87 (2H, m, H-9), 1.84 (1H, m, H-8a), 1.64 (1H, m, H-8b), 1.27 (3H, s, H-14), 1.25 (3H, s, H-12), 1.20 (3H, s, H-15), 1.17 (3H, s, H-13); 13C NMR (100 MHz, CD3COCD3) δ: 111.4 (t, C-1), 146.8 (d, C-2), 72.8 (s, C-3), 46.2 (t, C-4), 123.8 (d, C-5), 139.5 (s, C-6), 83.6 (s, C-7), 38.0 (t, C-8), 27.4 (t, C-9), 85.3 (d, C-10), 79.3 (s, C-11), 22.7 (q, C-12), 23.1 (q, C-13), 27.5 (q, C-14), 27.6 (q, C-15), 98.4 (d, C-1'), 75.0 (d, C-2'), 78.2 (d, C-3'), 71.8 (d, C-4'), 77.0 (d, C-5'), 63.1 (t, C-6').
Compound 2: colorless oil .UV (MeOH) λmax (log ε): 203 (3.5) nm; CD (MeOH) λmax(Dε): 190 (+4.9), 218 (-1.9) nm; 1H NMR (400 MHz, CD3COCD3) δ: 5.94 (1H, dd, J = 17.3, 10.7 Hz, H-2), 5.72 (1H, dt, J = 15.7, 6.8 Hz, H-5), 5.64 (1H, brd, J = 15.7 Hz, H-6), 5.19 (1H, dd, J = 17.3, 1.9 Hz, H-1a), 4.95 (1H, dd, J = 10.7, 1.9 Hz, H-1b), 4.58 (1H, d, J = 7.7 Hz, H-1'), 3.93 (1H, t, J = 6.9 Hz, H-10), 3.79 (1H, brd, J = 11.4 Hz, H-6'a), 3.61 (1H, dd, J = 11.4, 4.4 Hz, H-6'b), 3.39 (1H, t, J = 8.5 Hz, H-3'), 3.31 (1H, overlap, H-4'), 3.29 (1H, m, H-5'), 3.11 (1H, dd, J = 8.7, 7.8 Hz, H-2'), 2.22 (2H, m, H-4), 1.91 (2H, m, H-9), 1.83 (1H, m, H-8a), 1.72 (1H, m, H-8b), 1.26 (3H, s, H-12), 1.23 (3H, s, H-14), 1.20 (3H, s, H-15), 1.19 (3H, s, H-13); 13C NMR (100 MHz, CD3COCD3) δ: 111.4 (t, C-1), 146.7 (d, C-2), 72.9 (s, C-3), 46.3 (t, C-4), 123.5 (d, C-5), 140.5 (s, C-6), 83.3 (s, C-7), 38.7 (t, C-8), 27.4 (t, C-9), 85.5 (d, C-10), 79.3 (s, C-11), 22.8 (q, C-12), 23.5 (q, C-13), 26.5 (q, C-14), 27.7 (q, C-15), 98.4 (d, C-1'), 75.1 (d, C-2'), 78.3 (d, C-3'), 71.8 (d, C-4'), 77.1 (d, C-5'), 63.1 (t, C-6').
Compound 3: colorless oil .UV (MeOH) λmax (log ε): 203 (3.7) nm; CD (MeOH) λmax(Dε): 190 (+3.9), 218 (-1.0) nm; 1H NMR (400 MHz, CD3OD) δ: 5.84 (1H, dd, J = 17.3, 10.7 Hz, H-2), 5.56 (1H, dt, J = 15.5, 6.8 Hz, H-5), 5.38 (1H, brd, J = 15.5 Hz, H-6), 5.09 (1H, dd, J = 17.3, 1.9 Hz, H-1a), 4.85 (1H, dd, J = 10.7, 1.9 Hz, H-1b), 4.28 (1H, d, J = 7.8 Hz, H-1'), 3.83 (1H, t, J = 7.0 Hz, H-10), 3.64 (1H, brd, J = 11.4 Hz, H-6'a), 3.50 (1H, dd, J = 11.4, 4.4 Hz, H-6'b), 3.25 (1H, m, H-5'), 3.20 (1H, overlap, H-4'), 3.10 (1H, t, J = 8.5 Hz, H-3'), 3.03 (1H, dd, J = 8.7, 7.8 Hz, H-2'), 2.16 (2H, m, H-4), 1.75 (2H, m, H-9), 1.78 (2H, m, H-8), 1.16 (3H, s, H-15), 1.07 (3H, s, H-14), 1.05 (3H, s, H-12), 1.01 (3H, s, H-13); 13C NMR (100 MHz, CD3OD) δ: 111.5 (t, C-1), 146.7 (d, C-2), 80.3 (s, C-3), 46.3 (t, C-4), 123.6 (d, C-5), 139.8 (s, C-6), 83.5 (s, C-7), 38.7 (t, C-8), 27.4 (t, C-9), 85.9 (d, C-10), 72.7 (s, C-11), 27.1 (q, C-12), 26.1 (q, C-13), 26.9 (q, C-14), 27.7 (q, C-15), 98.9 (d, C-1'), 75.1 (d, C-2'), 78.2 (d, C-3'), 71.8 (d, C-4'), 77.1 (d, C-5'), 63.1 (t, C-6').
Compound 4: colorless oil .UV (MeOH) λmax (log ε): 203 (3.6) nm; CD (MeOH) λmax(Dε): 190 (+4.5), 218 (-0.9) nm; 1H NMR (400 MHz, CD3OD) δ: 5.84 (1H, dd, J = 17.3, 10.7 Hz, H-2), 5.53 (1H, dt, J = 15.5, 6.8 Hz, H-5), 5.35 (1H, brd, J = 15.5 Hz, H-6), 5.09 (1H, dd, J = 17.3, 1.9 Hz, H-1a), 4.85 (1H, dd, J = 10.7, 1.9 Hz, H-1b), 4.28 (1H, d, J = 7.8 Hz, H-1'), 3.73 (1H, t, J = 7.0 Hz, H-10), 3.64 (1H, brd, J = 11.4 Hz, H-6'a), 3.50 (1H, dd, J = 11.4, 4.4 Hz, H-6'b), 3.25 (1H, m, H-5'), 3.20 (1H, overlap, H-4'), 3.10 (1H, t, J = 8.5 Hz, H-3'), 3.03 (1H, dd, J = 8.7, 7.8 Hz, H-2'), 2.15 (2H, m, H-4), 1.76 (2H, m, H-9), 1.80 (2H, m, H-8), 1.16 (3H, s, H-15), 1.08 (3H, s, H-14), 1.05 (3H, s, H-12), 1.02 (3H, s, H-13); 13C NMR (100 MHz, CD3OD) δ: 111.5 (t, C-1), 146.7 (d, C-2), 80.2 (s, C-3), 46.2 (t, C-4), 123.7 (d, C-5), 139.5 (s, C-6), 83.7 (s, C-7), 38.2 (t, C-8), 27.4 (t, C-9), 85.7 (d, C-10), 72.7 (s, C-11), 27.1 (q, C-12), 26.1 (q, C-13), 27.8 (q, C-14), 27.6 (q, C-15), 98.8 (d, C-1'), 75.1 (d, C-2'), 78.1 (d, C-3'), 71.8 (d, C-4'), 77.1 (d, C-5'), 63.0 (t, C-6').
Compound 5: colorless oil .UV (MeOH) λmax (log ε): 203 (3.7) nm; CD (MeOH) λmax(Dε): 190 (+2.9), 204 (+0.7), 224 (-1.0) nm; 1H NMR (400 MHz, CD3OD) δ: 5.86 (1H, dd, J = 17.4, 10.8 Hz, H-2), 5.14 (1H, dd, J = 17.4, 1.6 Hz, H-1a), 5.13 (1H, overlap, H-6), 4.98 (1H, dd, J = 10.8, 1.6 Hz, H-1b), 4.45 (1H, d, J = 7.8 Hz, H-1'), 3.77 (1H, dd, J = 11.9, 2.1 Hz, H-6'a), 3.60 (1H, dd, J = 11.9, 5.3 Hz, H-6'b), 3.38 (1H, dd, J = 10.5, 1.4 Hz, H-10), 3.31 (1H, overlap, H-4'), 3.26 (1H, overlap, H-3'), 3.21 (1H, m, H-5'), 3.11 (1H, dd, J = 8.7, 7.8 Hz, H-2'), 2.18 (1H, m, H-8a), 1.98 (3H, overlap, H-5, 8b), 1.56 (3H, s, H-14), 1.55 (1H, m, H-9a), 1.46 (2H, m, H-4), 1.32 (1H, m, H-9b), 1.20 (3H, s, H-15), 1.17 (3H, s, H-13), 1.16 (3H, s, H-12); 13C NMR (100 MHz, CD3OD) δ: 112.0 (t, C-1), 146.3 (d, C-2), 73.9 (s, C-3), 43.4 (t, C-4), 23.7 (t, C-5), 126.0 (d, C-6), 135.9 (s, C-7), 37.8 (t, C-8), 30.6 (t, C-9), 78.0 (d, C-10), 81.8 (s, C-11), 21.3 (q, C-12), 23.8 (q, C-13), 16.0 (q, C-14), 27.6 (q, C-15), 98.5 (d, C-1'), 75.1 (d, C-2'), 77.6 (d, C-3'), 71.5 (d, C-4'), 77.6 (d, C-5'), 62.5 (t, C-6').
Compound 6: colorless oil .UV (MeOH) λmax (log ε): 203 (3.7) nm; CD (MeOH) λmax(Dε): 191 (-2.8), 223 (-0.9) nm; 1H NMR (400 MHz, CD3OD) δ: 5.88 (1H, dd, J = 17.8, 11.0 Hz, H-2), 5.18 (1H, dd, J = 17.8, 1.2 Hz, H-1a), 5.15 (1H, dd, J = 11.0, 1.2 Hz, H-1b), 5.11 (1H, overlap, H-6), 4.29 (1H, d, J = 7.8 Hz, H-1'), 3.75 (1H, dd, J = 11.9, 2.3 Hz, H-6'a), 3.57 (1H, dd, J = 11.9, 5.7 Hz, H-6'b), 3.26 (1H, overlap, H-3'), 3.22 (1H, t, J = 8.7 Hz, H-4'), 3.17 (1H, dd, J = 10.6, 1.5 Hz, H-10), 3.11 (1H, overlap, H-5'), 3.10 (1H, overlap, H-2'), 2.18 (1H, m, H-8a), 1.99 (2H, m, H-5), 1.96 (1H, m, H-8b), 1.65 (1H, m, H-9a), 1.55 (2H, t, J = 8.1 Hz, H-4), 1.55 (3H, s, H-14), 1.33 (3H, s, H-15), 1.27 (1H, m, H-9b), 1.10 (3H, s, H-12), 1.07 (3H, s, H-13); 13C NMR (100 MHz, CD3OD) δ: 115.8 (t, C-1), 144.5 (d, C-2), 81.4 (s, C-3), 42.6 (t, C-4), 23.6 (t, C-5), 125.8 (d, C-6), 136.0 (s, C-7), 37.8 (t, C-8), 30.7 (t, C-9), 78.9 (d, C-10), 73.8 (s, C-11), 25.7 (q, C-12), 24.9 (q, C-13), 16.1 (q, C-14), 23.1 (q, C-15), 99.5 (d, C-1'), 75.2 (d, C-2'), 78.2 (d, C-3'), 71.7 (d, C-4'), 77.6 (d, C-5'), 62.8 (t, C-6').
Compound 7: colorless oil .UV (MeOH) λmax (log ε): 203 (3.7) nm; CD (MeOH) λmax(Dε): 192 (+1.8), 222 (-0.3) nm; 1H NMR (400 MHz, CD3COCD3) δ: 5.92 (1H, dd, J = 17.3, 10.7 Hz, H-2), 5.27 (1H, overlap,H-6), 5.20 (1H, dd, J = 17.3, 1.9 Hz, H-1a), 4.96 (1H, dd, J = 10.7, 1.9 Hz, H-1b), 4.50 (1H, d, J = 7.9 Hz, H-1'), 3.85 (1H, dd, J = 11.2, 2.1 Hz, H-6'a), 3.72 (1H, dd, J = 11.2, 5.6 Hz, H-6'b), 3.42‒3.25 (5H, overlap, H-10, 2', 3', 4', 5'), 2.28 (1H, m, H-8a), 2.16 (1H, m, H-8b), 2.03 (2H, m, H-5), 1.58 (3H, s, H-14), 1.54 (3H, overlap, H-4, 9a), 1.38 (1H, m, H-9b), 1.23 (3H, s, H-15), 1.12 (3H, s, H-12), 1.09 (3H, s, H-13); 13C NMR (100 MHz, CD3COCD3) δ: 111.3 (t, C-1), 146.7 (d, C-2), 73.8 (s, C-3), 43.3 (t, C-4), 23.3 (t, C-5), 125.9 (d, C-6), 135.3 (s, C-7), 36.5 (t, C-8), 30.4 (t, C-9), 90.3 (d, C-10), 72.9 (s, C-11), 23.8 (q, C-12), 26.5 (q, C-13), 16.1 (q, C-14), 28.3 (q, C-15), 106.1 (d, C-1'), 75.6 (d, C-2'), 77.1 (d, C-3'), 71.5 (d, C-4'), 78.2 (d, C-5'), 62.8 (t, C-6').
Compound 8: colorless oil .UV (MeOH) λmax (log ε): 204 (3.9) nm; CD (MeOH) λmax(Dε): 191 (+8.7), 215 (-2.3) nm; 1H NMR (400 MHz, CDCl3) δ: 5.83 (1H, dd, J = 17.3, 10.7 Hz, H-2), 5.60 (1H, d, J = 15.8 Hz, H-6), 5.54 (1H, m, H-6), 5.12 (1H, dd, J = 17.4, 1.3 Hz, H-1a), 4.96 (1H, dd, J = 10.7, 1.3 Hz, H-1b), 3.77 (1H, t, J = 7.0 Hz, H-10), 2.30 (2H, m, H-4), 2.17 (2H, m, H-9), 1.80 (1H, m, H-8a), 1.70 (1H, m, H-8b), 1.23 (3H, s, H-14), 1.18 (3H, s, H-12), 1.15 (3H, s, H-15), 1.04 (3H, s, H-13); 13C NMR (100 MHz, CDCl3) δ: 111.9 (t, C-1), 144.8 (d, C-2), 72.6 (s, C-3), 45.1 (t, C-4), 122.6 (d, C-5), 140.6 (d, C-6), 82.5 (s,C-7), 38.3 (t, C-8), 26.5 (t, C-9), 85.6 (d, C-10), 71.3 (s, C-11), 27.3 (q, C-12), 24.5 (q, C-13), 26.5 (q, C-14), 27.4 (q, C-15).
Compound 9: colorless oil .UV (MeOH) λmax (log ε): 204 (3.9) nm; CD (MeOH) λmax(Dε): 190 (+10.8), 215 (-0.8) nm; 1H NMR (400 MHz, CDCl3) δ: 5.86 (1H, dd, J = 17.3, 10.7 Hz, H-2), 5.52 (2H, overlap, H-5, 6), 5.14 (1H, dd, J = 17.3, 1.4 Hz, H-1a), 4.99 (1H, dd, J = 10.7, 1.4 Hz, H-1b), 3.72 (1H, t, J = 7.1 Hz, H-10), 2.22 (2H, m, H-4), 1.78 (3H, m, H-8a, 9), 1.64 (1H, m, H-8b), 1.26 (3H, s, H-14), 1.20 (3H, s, H-12), 1.15 (3H, s, H-15), 1.07 (3H, s, H-13); 13C NMR (100 MHz, CDCl3) δ: 111.9 (t, C-1), 144.8 (d, C-2), 72.6 (s, C-3), 45.1 (t, C-4), 122.3 (d, C-5), 139.9 (d, C-6), 82.8 (s,C-7), 37.8 (t, C-8), 26.5 (t, C-9), 85.5 (d, C-10), 71.4 (s, C-11), 27.2 (q, C-12), 24.1 (q, C-13), 27.0 (q, C-14), 27.2 (q, C-15).
Compound 10: colorless oil .UV (MeOH) λmax (log ε): 203 (3.8) nm; CD (MeOH) λmax (Dε): 191 (+2.9), 204 (+0.7), 224 (-1.1) nm; 1H NMR (400 MHz, CDCl3) δ: 5.90 (1H, dd, J = 17.4, 10.8 Hz, H-2), 5.18 (1H, dd, J = 17.4, 1.6 Hz, H-1a), 5.20 (1H, overlap, H-6), 5.05 (1H, dd, J = 10.8, 1.6 Hz, H-1b), 3.35 (1H, dd, J = 10.5, 1.4 Hz, H-10), 2.08 (1H, overlap, H-5), 2.06 (2H, overlap, H-8), 1.59 (3H, s, H-14), 1.55 (3H, overlap, H-4a, 9), 1.38 (1H, m, H-4b), 1.28 (3H, s, H-15), 1.17 (3H, s, H-13), 1.14 (3H, s, H-12); 13C NMR (100 MHz, CDCl3) δ: 111.9 (t, C-1), 145.0 (d, C-2), 73.5 (s, C-3), 41.9 (t, C-4), 22.7 (t, C-5), 125.1 (d, C-6), 135.4 (s, C-7), 36.8 (t, C-8), 29.6 (t, C-9), 78.3 (d, C-10), 72.8 (s, C-11), 26.4 (q, C-12), 23.2 (q, C-13), 16.0 (q, C-14), 27.8 (q, C-15).
Example 3:
Detection of anti-trichina Activity of the Compounds of the invention:
After one week of adaptive feeding of male Kunming mice, each mouse was perfused with a physiological saline suspension containing 200 trichina larvae. The model group was perfused with 0.5% CMC-Na after 3 h of infection and the group was perfused with the corresponding dose of compound. After the continuous administration of 7 d and the last administration of 24: 24 h, the mice were dissected from the small intestine, the contents were removed, dissected along the middle of the small intestine and cut into small sections of about 2 cm, placed in physiological saline, incubated at 37 ℃ for 3 hours, and the adult counts were collected and the rate of reduction was calculated. The insect-reducing rate is calculated according to the following formula: percent reduction = [1- (mean number of insects in model group-mean number of insects in dosing group)/(mean number of insects in model group) ]100.
The activity data are shown in Table 1.
Data on anti-trichina activity of compounds 1-10 (mean±s, n=5)
Example 4:
Tablet: 1-10 mg of either of the compounds obtained in examples 1 and 2, lactose 180 mg, starch 55 mg, magnesium stearate 5 mg;
The preparation method comprises the following steps: mixing the compound, lactose and starch, uniformly wetting with propylene glycol, sieving the wetted mixture, drying, sieving again, adding magnesium stearate, tabletting the mixture, and each tablet having a weight of 250 mg and a compound content of 10 mg.
Example 5:
Ampoule agent: 1-10 mg of any one of the compounds obtained in examples 1 and 2;
The preparation method comprises the following steps: any one of the compounds 1 to 10 obtained in examples 1 and 2 was dissolved in 3 mL propylene glycol, and the resulting solution was filtered and filled into ampoule bottles under aseptic conditions.
Example 6:
The capsule comprises the following components: 1-10 mg of either of the compounds obtained in examples 1 and 2, 187-mg mg of lactose, 3-mg of magnesium stearate;
The preparation method comprises the following steps: the compound was mixed with adjuvants, sieved, mixed homogeneously, and the resulting mixture was filled into hard gelatin capsules, each capsule having an active ingredient content of 10 mg, 200 mg.
Claims (2)
1. The application of the farnesane sesquiterpenoids in preparing the preparation for resisting trichinosis,
2. The use of any one of the compounds of claim 1 for the preparation of an anti-trichinosis medicament.
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