CN109810153B - Preparation method and analgesic application of aromatic substituted glucose compound and pharmaceutical composition thereof - Google Patents
Preparation method and analgesic application of aromatic substituted glucose compound and pharmaceutical composition thereof Download PDFInfo
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Abstract
The invention relates to a preparation method and analgesic application of an aromatic substituted glucose compound and a pharmaceutical composition thereof, belonging to the field of natural pharmaceutical chemistry. Aromatic substituted glucose compounds 1-14, pharmaceutical composition containing the same as active ingredient, and its preparation methodTernstroemia gymnanthera(Wight et Arn.)Bedd.]The above-ground parts or the whole plant of the plant are directly extracted by using an organic solvent dichloromethane or chloroform or ethyl acetate or acetone or methanol or ethanol or water through cold soaking or hot reflux or ultrasonic or microwave-assisted extraction, or are extracted by using the organic solvent or water through cold soaking or reflux or ultrasonic or microwave-assisted extraction and then using ethyl acetate to obtain a total extract, and the compound of the invention is obtained by repeatedly carrying out chromatography on the total extract. The analgesic drug compound contains the compound of the invention as an active ingredient. The application of the compound in preparing analgesic.
Description
The technical field is as follows:
the invention belongs to the field of natural medicinal chemistry, and particularly relates to an aromatic substituted glucose compound, a preparation method thereof, a medicinal composition taking the compound as an active ingredient, and application thereof in analgesia.
Technical background:
cortex magnoliae officinalis [ Ternstroemia gymntnhera (Wight et Arn.) Bedd ] heterophylla, Callicarpa diffusa, Moringa mangachapoi, camellia, Thymus suis, caulis seu radix Schisandrae sinensis, Kadsura longipedunculata, and the like, is shrub or small tree of genus Callicarpa of family Theaceae, and is 1.5-10 m high, and sometimes 15m high. The compound fertilizer is widely distributed in places such as Huining, Zhejiang, Jiangxi, Fujian, northwest of Hubei, southern and northwest of Hunan, Guangdong, northern and eastern Guangxi, Yunnan, the Bijie of northeast and northwest of Guizhou, southern Sichuan and the like in south of Anhui of China, and is mostly grown in mountain forests with the elevation of 200-1400 meters (Yunnan can be distributed in 2000-2800 meters), forest borders and roadside or sparse forests near mountain tops. The leaves and the whole plant of the cortex magnoliae officinalis recorded in Chinese materia medica have the effects of clearing away heat and toxic materials, dissipating blood stasis and reducing swelling. It is used for treating skin sore, carbuncle, toxic swelling, and acute mastitis; the flower of the plant has effects of killing parasite and relieving itching, and can be used for treating scabies, tinea and pruritus. At present, the main components of Japanese Katsumadai incense are triterpenoids and a small amount of phenolic acid compounds with simple structures (Tori M, et al., letters in Organic Chemistry,2005,2(3): 262-. However, no research report on aromatic substituted glucose compounds in the cortex magnoliae officinalis and analgesic activity thereof is found at home and abroad.
The invention content is as follows:
the invention aims to provide aromatic substituted glucose compounds, a pharmaceutical composition taking the aromatic substituted glucose compounds as active ingredients, a preparation method of the aromatic substituted glucose compounds and application of the aromatic substituted glucose compounds in preparation of analgesics.
The above object of the present invention is achieved by the following technical solutions:
aromatic substituted glucose compounds 1-14 represented by the following structures:
a preparation method of the compounds 1-14 comprises the steps of taking aerial parts or whole plants of a camellia [ Ternststoemia gymnanthhera (Wight et Arn.) Bedd ] plant, directly cold soaking or hot reflux or ultrasonic or microwave-assisted extraction by using an organic solvent dichloromethane or chloroform or ethyl acetate or acetone or methanol or ethanol or water, or extracting by using the organic solvent or water for cold soaking or reflux or ultrasonic or microwave-assisted extraction and then using ethyl acetate for extraction to obtain a total extract, and repeatedly carrying out column chromatography on the total extract to obtain the compounds 1-14.
The process for the preparation of the compounds 1 to 14 according to the invention is more particularly carried out by:
a: dichloromethane or chloroform or ethyl acetate or acetone or methanol or ethanol or water is directly cold-soaked or hot-refluxed or ultrasonically or microwave-assisted to extract aerial parts or whole plants of a Kadsura longipedera (Wight et Arn.) Bedd.) plant to obtain a total extract, ethyl acetate is extracted to obtain an ethyl acetate extract, and the compounds 1-14 can be obtained by repeated column chromatography.
B: extracting aerial part or whole plant coarse powder of Kadsura longipedunculata (Wight et Arn.) with organic solvent (such as chloroform, methanol, ethanol, acetone, dichloromethane, etc.) by cold soaking or hot reflux or ultrasound or microwave assistance to obtain total extract, and repeatedly performing column chromatography to obtain compounds 1-14.
More specifically, the compounds 1-14 are prepared by drying aerial parts or whole plant of Kadsura longipedera (Wight et Arn.) Ohwi in shade, pulverizing to 20-30 mesh, extracting with 95% ethanol at room temperature for 3 times each for 24h, mixing extractive solutions, concentrating under reduced pressure to obtain extract, suspending with appropriate amount of water, distributing with ethyl acetate for several times to obtain ethyl acetate extract, dissolving the extract with appropriate amount of chloroform/acetone, mixing with silica gel 80-100 mesh, subjecting to column chromatography with 200-300 mesh silica gel, subjecting to column chromatography with 1:0-0:1 chloroform/acetone or 1:0-0:1 chloroform/methanol to obtain 7 main parts, subjecting to silica gel column chromatography with 9:1 chloroform/methanol part, 8:2 chloroform/methanol part and 7:3 chloroform/methanol part, performing gradient elution with chloroform/acetone at ratio of 100:1-1:1 to obtain 10 fractions, and performing repeated silica gel, RP-18 and Sephadex LH-20 column chromatography to obtain compounds 1-14.
An analgesic comprising a compound of any one of compounds 1 to 14 and conventional adjuvants.
A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of compounds 1-14 and a pharmaceutically acceptable carrier.
Use of any one of compounds 1-14 in the preparation of an analgesic medicament.
The invention provides a pharmaceutical composition for analgesia, which comprises any one of compounds 1-14 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 in the form of compositions by oral, nasal, rectal or parenteral administration to a patient in need of such treatment. For oral administration, it can be made 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 prepared into a solution for injection, etc. Preferred forms are tablets, capsules and injections.
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, the active ingredient may be combined with one or more carriers and then formulated into the desired dosage form.
The pharmaceutical compositions of the present invention preferably contain 0.1% to 99.5% by weight of the active ingredient, most preferably 0.5% to 95% by weight of the active ingredient.
The amount of the compound of the present invention to be administered may vary depending on the route of administration, age, body weight of the patient, type and severity of the disease to be treated, etc., and the daily dose may be 0.01 to 10mg/kg body weight, preferably 0.1 to 5mg/kg body weight. One or more administrations may be carried out.
The compound of the invention shows better analgesic activity.
The compounds 1-14 are screened for analgesic activity, and the compounds show better analgesic activity. In an analgesic activity application, compounds 1-14 are administered to a substrate or a population in an amount ranging from 1-1000 μ M, preferably from 10-200 μ M, optionally in combination with a carrier and/or vehicle.
The specific implementation mode is as follows:
the following examples are provided to further illustrate the essence of the present invention, which will enable a person skilled in the art to more fully understand the invention, but are not intended to limit the invention in any way.
Example 1:
extraction, isolation and purification of Compounds 1-14 of the invention:
drying aerial parts (14kg) of Kadsura longipedunculata (Wight et Arn.) Bedd. plant in shade, pulverizing to 30 mesh, extracting with 95% ethanol at room temperature for 3 times (60L and 24h each time), mixing extractive solutions, concentrating under reduced pressure to obtain extract, suspending with appropriate amount of water, distributing with ethyl acetate for 6 times to obtain ethyl acetate extract (726g), dissolving the extract with appropriate amount of chloroform/acetone, mixing with silica gel of 80-100 mesh, subjecting to column chromatography with 650g of silica gel of 200-300 mesh, subjecting to gradient elution with chloroform/methanol (1:0-0:1) to obtain 7 main parts, subjecting to silica gel column chromatography with 9:1 chloroform/methanol part, 8:2 chloroform/methanol part and 7:3 chloroform/methanol part, subjecting to gradient elution with 100:1-1:1 chloroform/acetone, resulting in 10 portions. Then respectively carrying out repeated silica gel, RP-18 and Sephadex LH-20 column chromatography to obtain the compounds 1-14.
Example 2:
physical and spectral data for compounds 1-14 of the present invention:
compound 1: brown solid. UV (MeOH) lambdamax(logε):223(4.11),290(3.55)nm；HR-ESI-MS m/z:329.3205[M-H]-(calcd for C14H17O9,329.3202)；1H-NMR(400MHz,CD3OD)δ:7.08(2H,d,J＝10.2Hz,H-2',6'),6.12(2H,d,J＝10.2Hz,H-3',5'),4.43(1H,dd,J＝11.9,2.1Hz,H-6a),4.15(1H,d,J＝7.8Hz,H-1),4.21(1H,overlap,H-6b),3.30(1H,overlap,H-5),3.25(1H,overlap,H-4),3.21(1H,overlap,H-3),3.13(1H,dd,J＝9.0,7.8Hz,H-2),2.75(2H,s,H2-7')；13C-NMR(100MHz,CD3OD)δ:102.3(d,C-1),75.1(d,C-2),77.9(d,C-3),71.4(d,C-4),78.2(d,C-5),64.6(d,C-6),68.1(s,C-1'),152.3(d,C-2',6'),128.0(d,C-3',5'),187.6(s,C-4'),45.5(t,C-7'),170.9(s,C-8')。
Compound 2: brown solid. UV (MeOH) lambdamax(logε):222(4.03),290(3.48)nm；HR-ESI-MS m/z:343.3505[M-H]-(calcd for C15H19O9,343.3512)；1H-NMR(400MHz,CD3OD)δ:6.74(1H,d,J＝2.1Hz,H-2'),6.69(1H,d,J＝8.1Hz,H-5'),6.59(1H,d,J＝8.1,2.1Hz,H-6'),4.45(1H,dd,J＝11.9,2.1Hz,H-6a),4.22(1H,overlap,H-6b),4.18(1H,d,J＝7.8Hz,H-1),3.85(3H,s,-OCH3),3.49(2H,s,H2-7'),3.44(1H,m,H-5),3.38(1H,overlap,H-3),3.35(1H,overlap,H-4),3.17(1H,dd,J＝9.1,7.8Hz,H-2)；13C-NMR(100MHz,CD3OD)δ:102.3(d,C-1),74.7(d,C-2),77.9(d,C-3),71.5(d,C-4),75.3(d,C-5),64.2(t,C-6),126.9(s,C-1'),117.5(d,C-2'),148.2(s,C-3'),146.5(s,C-4'),116.5(d,C-5'),121.6(d,C-6'),41.1(t,C-7'),173.9(s,C-8'),56.1(q,-OCH3)。
Compound 3: brown solid. UV (MeOH) lambdamax(logε):224(4.07),291(3.57)nm；HR-ESI-MS m/z:315.1514[M-H]-(calcd for C14H19O8,315.1513)；1H-NMR(400MHz,CD3OD)δ:6.64(1H,d,J＝2.1Hz,H-2'),6.58(1H,d,J＝8.1Hz,H-5'),6.48(1H,dd,J＝8.0,2.1Hz,H-6'),4.47(1H,dd,J＝11.9,2.1Hz,H-6a),4.24(1H,overlap,H-6b),4.16(1H,d,J＝7.8Hz,H-1),3.48(2H,overlap,H2-7”),3.46(1H,m,H-5),3.39(1H,overlap,H-3),3.34(1H,overlap,H-4),3.22(1H,dd,J＝9.1,7.8Hz,H-2)；13C-NMR(100MHz,CD3OD)δ:102.0(d,C-1),75.0(d,C-2),78.0(d,C-3),71.5(d,C-4),75.4(d,C-5),64.3(t,C-6),131.2(s,C-1'),116.2(d,C-2'),146.1(s,C-3'),144.3(s,C-4'),117.2(d,C-5'),121.4(d,C-6'),36.7(t,C-7'),72.1(t,C-8')。
Compound 4: brown solid. UV (MeOH) lambdamax(logε):223(4.22),291(3.84)nm；HR-ESI-MS m/z:465.1405[M-H]-(calcd for C22H25O11,465.1402)；1H-NMR(400MHz,CD3OD)δ:7.07(2H,d,J＝10.1Hz,H-2”,6”),6.11(2H,d,J＝10.1Hz,H-3”,5”),6.69(1H,d,J＝8.0Hz,H-5'),6.66(1H,d,J＝2.1Hz,H-2'),6.56(1H,dd,J＝8.0,2.1Hz,H-6'),4.44(1H,dd,J＝11.9,2.1Hz,H-6a),4.30(1H,d,J＝8.0Hz,H-1),4.19(1H,dd,J＝11.9,5.8Hz,H-6b),3.95(1H,overlap,H-8'a),3.68(1H,overlap,H-8'b),3.45(1H,overlap,H-5),3.37(1H,overlap,H-4),3.34(1H,overlap,H-3),3.19(1H,t,J＝8.4Hz,H-2),2.79(2H,overlap,H2-7'),2.77(2H,s,H2-7”)；13C-NMR(100MHz,CD3OD)δ:104.4(d,C-1),75.0(d,C-2),77.8(d,C-3),71.5(d,C-4),75.1(d,C-5),65.0(t,C-6),131.4(s,C-1'),117.1(d,C-2'),146.1(s C-3'),144.6(s,C-4'),116.3(d,C-5'),121.2(d,C-6'),36.6(t,C-7'),72.3(t,C-8'),68.0(s,C-1”),152.7(d,C-2”,6”),128.3(d,C-3”,5”),187.4(s,C-4”),45.8(t,C-7”),170.3(s,C-8”)。
Compound 5: brown solid. UV (MeOH) lambdamax(logε):223(4.32),291(3.85)nm；HR-ESI-MS m/z:465.1410[M-H]-(calcd for C23H29O10,465.1405)；1H-NMR(400MHz,CD3OD)δ:6.68(1H,overlap,H-5',5”),6.66(1H,overlap,H-2',2”),6.57(1H,dd,J＝7.9,2.1Hz,H-6',6”),4.43(1H,dd,J＝11.9,2.1Hz,H-6a),4.25(1H,d,J＝7.8Hz,H-1),4.21(1H,overlap,H-6b),3.87(2H,overlap,H-8'a,8”a),3.85(3H,s,-OCH3),3.63(2H,overlap,H-8'b,8”b),3.44(1H,m,H-5),3.35(1H,overlap,H-3),3.33(1H,overlap,H-4),3.18(1H,dd,J＝9.1,7.8Hz,H-2),2.76(4H,overlap,H2-7',7”)；13C-NMR(100MHz,CD3OD)δ:104.5(d,C-1),74.8(d,C-2),77.8(d,C-3),71.3(d,C-4),75.0(d,C-5),64.5(t,C-6),131.6(s,C-1'),116.2(d,C-2'),145.8(s C-3'),144.5(s,C-4'),117.3(d,C-5'),121.2(d,C-6'),36.6(t,C-7'),72.1(t,C-8'),130.8(s,C-1”),117.6(d,C-2”),146.5(s,C-3”),145.1(s,C-4”),116.0(d,C-5”),121.8(d,C-6”),36.4(t,C-7”),72.3(t,C-8”),56.2(q,-OCH3)。
Compound 6: brown solid.UV(MeOH)λmax(logε):223(4.25),291(3.79)nm；HR-ESI-MS m/z:451.1763[M-H]-(calcd for C22H27O10,451.1761)；1H-NMR(400MHz,CD3OD)δ:7.08(2H,d,J＝10.3Hz,H-2”,6”),6.13(2H,d,J＝10.3Hz,H-3”,5”),6.68(1H,d,J＝8.0Hz,H-5'),6.65(1H,d,J＝2.1Hz,H-2'),6.55(1H,dd,J＝8.0,2.1Hz,H-6'),4.45(1H,dd,J＝11.9,2.1Hz,H-6a),4.29(1H,d,J＝8.0Hz,H-1),4.20(1H,dd,J＝11.9,5.8Hz,H-6b),3.95(2H,overlap,H-8'a,8”a),3.65(2H,overlap,H-8'b,8”b),3.45(1H,overlap,H-5),3.37(1H,overlap,H-4),3.34(1H,overlap,H-3),3.19(1H,t,J＝8.4Hz,H-2),2.79(2H,overlap,H2-7'),1.75(2H,m,H2-7”)；13C-NMR(100MHz,CD3OD)δ:104.4(d,C-1),75.0(d,C-2),77.8(d,C-3),71.5(d,C-4),75.1(d,C-5),65.0(t,C-6),131.4(s,C-1'),117.1(d,C-2'),146.1(s C-3'),144.6(s,C-4'),116.3(d,C-5'),121.2(d,C-6'),36.6(t,C-7'),72.3(t,C-8'),68.0(s,C-1”),152.7(d,C-2”,6”),128.3(d,C-3”,5”),187.4(s,C-4”),36.8(t,C-7”),68.3(s,C-8”)。
Compound 7: brown solid. UV (MeOH) lambdamax(logε):223(4.25),291(3.70)nm；HR-ESI-MS m/z:479.3677[M-H]-(calcd for C22H23O12,479.3678)；1H-NMR(400MHz,CD3OD)δ:7.07(2H,d,J＝10.4Hz,H-2”,6”),6.10(2H,d,J＝10.4Hz,H-3”,5”),6.70(1H,d,J＝8.0Hz,H-5'),6.68(1H,d,J＝2.1Hz,H-2'),6.57(1H,dd,J＝8.0,2.1Hz,H-6'),4.45(1H,dd,J＝11.8,2.2Hz,H-6a),4.19(1H,dd,J＝11.8,5.8Hz,H-6b),4.16(1H,d,J＝8.0Hz,H-1),3.93(1H,overlap,H-8'a),3.86(3H,s,-OCH3),3.63(1H,overlap,H-8'b),3.51(1H,overlap,H-5),3.39(1H,overlap,H-4),3.36(1H,overlap,H-3),3.19(1H,t,J＝8.4Hz,H-2),2.79(2H,s,H2-7”)；13C-NMR(100MHz,CD3OD)δ:101.9(d,C-1),75.2(d,C-2),79.8(d,C-3),71.2(d,C-4),75.0(d,C-5),65.2(t,C-6),131.2(s,C-1'),117.0(d,C-2'),147.1(s C-3'),145.6(s,C-4'),116.3(d,C-5'),122.2(d,C-6'),171.6(s,C-7'),68.1(s,C-1”),152.8(d,C-2”,6”),128.3(d,C-3”,5”),187.5(s,C-4”),45.7(t,C-7”),170.5(s,C-8”),56.2(q,-OCH3)。
Compound 8: brown solid. UV (MeOH) lambdamax(logε):220(4.38),292(3.99)nm；HR-ESI-MS m/z:615.1702[M-H]-(calcd for C30H31O14,615.1719)；1H-NMR(400MHz,CD3OD)δ:6.76(1H,d,J＝2.1Hz,H-2”),6.74(1H,d,J＝2.1Hz,H-2”'),6.72(1H,d,J＝8.5Hz,H-5”),6.70(2H,d,J＝8.6Hz,H-5',5”'),6.65(1H,d,J＝2.1Hz,H-2'),6.58(1H,overlap,H-6”),6.57(1H,overlap,H-6”'),6.51(1H,d,J＝8.1,2.1Hz,H-6'),4.71(1H,dd,J＝9.2,8.0Hz,H-2),4.42(1H,dd,J＝11.9,2.0Hz,H-6a),4.34(1H,d,J＝8.0Hz,H-1),4.23(1H,dd,J＝11.9,5.9Hz,H-6b),3.78(1H,dd,J＝9.4,6.9Hz,H-8'a),3.48(2H,s,H2-7”'),3.54(1H,t,J＝9.2Hz,H-3),3.45(2H,overlap,H-5,8'b),3.43(2H,s,H2-7”),3.39(1H,t,J＝9.2Hz,H-4),2.54(2H,m,H2-7')；13C-NMR(100MHz,CD3OD)δ:101.9(d,C-1),75.0(d,C-2),75.6(d,C-3),71.5(d,C-4),75.0(d,C-5),64.6(t,C-6),131.6(s,C-1'),117.1(d,C-2'),145.6(s C-3'),144.2(s,C-4'),116.3(d,C-5'),121.4(d,C-6'),36.0(t,C-7'),71.7(t,C-8'),126.8(s,C-1”),117.5(d,C-2”),145.9(s,C-3”),145.1(s,C-4”),116.2(d,C-5”),121.8(d,C-6”),41.2(t,C-7”),173.1(s,C-8”),126.7(s,C-1”'),117.3(d,C-2”'),145.9(s,C-3”'),145.1(s,C-4”'),116.1(d,C-5”'),121.7(d,C-6”'),41.1(t,C-7”'),173.9(s,C-8”')。
Compound 9: brown solid. UV (MeOH) lambdamax(logε):222(4.58),291(3.99)nm；HR-ESI-MS m/z:599.1832[M-H]-(calcd for C31H35O12,599.1832)；1H-NMR(400MHz,CD3OD)δ:7.08(2H,d,J＝8.1Hz,H-2”,6”),6.74(2H,d,J＝8.1Hz,H-3”,5”),6.72(1H,d,J＝2.1Hz,H-2”'),6.70(1H,d,J＝8.3Hz,H-5”'),6.68(1H,d,J＝8.1Hz,H-5'),6.65(1H,d,J＝2.1Hz,H-2'),6.57(1H,overlap,H-6”'),6.52(1H,d,J＝8.1,2.1Hz,H-6'),4.72(1H,dd,J＝9.1,8.0Hz,H-2),4.41(1H,dd,J＝11.8,2.0Hz,H-6a),4.35(1H,d,J＝8.0Hz,H-1),4.22(1H,dd,J＝11.8,5.9Hz,H-6b),3.87(3H,s,-OCH3),3.78(2H,overlap,H-8'a,8”'a),3.54(1H,t,J＝9.2Hz,H-3),3.45(3H,overlap,H-5,8'b,8”'b),3.47(2H,s,H2-7”),3.38(1H,t,J＝9.2Hz,H-4),2.55(4H,overlap,H2-7',7”')；13C-NMR(100MHz,CD3OD)δ:102.2(d,C-1),75.1(d,C-2),75.7(d,C-3),71.5(d,C-4),74.9(d,C-5),64.8(t,C-6),131.8(s,C-1'),117.2(d,C-2'),145.3(s C-3'),144.4(s,C-4'),116.2(d,C-5'),121.4(d,C-6'),36.1(t,C-7'),71.7(t,C-8'),126.9(s,C-1”),117.5(d,C-2”),145.9(s,C-3”),145.1(s,C-4”),116.3(d,C-5”),121.5(d,C-6”),41.2(t,C-7”),173.0(s,C-8”),131.7(s,C-1”'),117.3(d,C-2”'),147.9(s,C-3”'),145.2(s,C-4”'),116.1(d,C-5”'),121.7(d,C-6”'),36.4(t,C-7”'),72.0(t,C-8”'),56.7(q,-OCH3)。
Compound 10: brown solid. UV (MeOH) lambdamax(logε):223(4.27),291(3.82)nm；HR-ESI-MS m/z:615.1714[M-H]-(calcd for C30H31O14,615.1719)；1H-NMR(400MHz,CD3OD)δ:7.06(2H,d,J＝10.1Hz,H-2”',6”'),6.72(1H,d,J＝8.1Hz,H-5'),6.77(1H,d,J＝2.0Hz,H-2”),6.69(1H,d,J＝8.0Hz,H-5”),6.64(1H,d,J＝2.0Hz,H-2'),6.60(1H,dd,J＝8.0,2.0Hz,H-6”),6.51(1H,d,J＝8.0,2.0Hz,H-6'),6.12(2H,d,J＝10.1Hz,H-3”',5”'),4.71(1H,dd,J＝9.6,8.0Hz,H-2),4.44(1H,m,H-6a),4.40(1H,d,J＝8.0Hz,H-1),4.21(1H,dd,J＝11.9,5.3Hz,H-6b),3.85(1H,m,H-8'a),3.56(1H,t,J＝9.2Hz,H-3),3.46(2H,s,H2-7”),3.45(2H,overlap,H-5,8'b),3.37(1H,overlap,H-4),2.75(2H,s,H2-7”'),2.54(2H,t,J＝7.3Hz,H2-7')；13C-NMR(100MHz,CD3OD)δ:101.9(d,C-1),75.0(d,C-2),75.5(d,C-3),71.4(d,C-4),74.8(d,C-5),64.6(t,C-6),131.3(s,C-1'),117.0(d,C-2'),145.6(s C-3'),144.2(s,C-4'),116.1(d,C-5'),121.8(d,C-6'),36.1(t,C-7'),71.8(t,C-8'),126.8(s,C-1”),117.5(d,C-2”),145.9(s,C-3”),145.1(s,C-4”),116.2(d,C-5”),121.3(d,C-6”),41.3(t,C-7”),173.0(s,C-8”),67.9(s,C-1”'),152.6(d,C-2”',6”'),128.1(d,C-3”',5”'),187.4(s,C-4”'),45.5(t,C-7”'),170.2(s,C-8”')。
Compound 11: brown solid. UV (MeOH) lambdamax(logε):224(4.33),285(3.75)nm；HR-ESI-MS m/z:599.1766[M-H]-(calcd for C30H31O13,599.1770)；1H-NMR(400MHz,CD3OD)δ:7.08(2H,overlap,H-2”,6”),7.07(2H,overlap,H-2”',6”'),6.68(1H,overlap,H-5'),6.74(1H,d,J＝8.2Hz,H-3”,5”),6.64(1H,overlap,H-2'),6.50(1H,d,J＝8.2,2.4Hz,H-6'),6.13(2H,d,J＝10.1Hz,H-3”',5”'),4.71(1H,overlap,H-2),4.44(1H,overlap,H-6a),4.40(1H,d,J＝8.2Hz,H-1),4.21(1H,dd,J＝12.1,5.5Hz,H-6b),3.85(1H,overlap,H-8'a),3.54(1H,overlap,H-3),3.51(2H,s,H2-7”),3.47(2H,overlap,H-5,8'b),3.40(1H,overlap,H-4),2.76(2H,s,H2-7”'),2.56(2H,t,J＝7.3Hz,H2-7')；13C-NMR(100MHz,CD3OD)δ:101.9(d,C-1),75.1(d,C-2),75.6(d,C-3),71.5(d,C-4),75.0(d,C-5),64.7(t,C-6),131.4(s,C-1'),117.1(d,C-2'),145.9(s C-3'),144.5(s,C-4'),116.1(d,C-5'),121.3(d,C-6'),36.2(t,C-7'),71.8(t,C-8'),126.3(s,C-1”),131.4(d,C-2”,6”),116.1(d,C-3”,C-5”),157.2(s,C-4”),41.1(t,C-7”),173.1(s,C-8”),68.0(s,C-1”'),152.7(d,C-2”',6”'),128.2(d,C-3”',5”'),187.5(s,C-4”'),45.6(t,C-7”'),170.2(s,C-8”')。
Compound 12: brown solid. UV (MeOH) lambdamax(logε):222(4.68),291(3.89)nm；HR-ESI-MS m/z:611.1122[M-H]-(calcd for C31H31O13,611.1123)；1H-NMR(400MHz,CD3OD)δ:7.61(1H,d,J＝15.7Hz H-7”),7.48(2H,d,J＝8.3Hz,H-2”,6”),7.08(2H,d,J＝10.1Hz,H-2”',6”'),6.87(2H,d,J＝8.3Hz,H-3”,5”),6.68(1H,overlap,H-5'),6.64(1H,overlap,H-2'),6.50(1H,d,J＝8.2,2.4Hz,H-6'),6.37(1H,d,J＝15.7Hz,H-8”),6.12(2H,d,J＝10.1Hz,H-3”',5”'),4.72(1H,overlap,H-2),4.41(1H,overlap,H-6a),4.40(1H,d,J＝8.2Hz,H-1),4.23(1H,dd,J＝12.1,5.5Hz,H-6b),3.85(1H,overlap,H-8'a),3.53(1H,overlap,H-3),3.49(2H,overlap,H-5,8'b),3.42(1H,overlap,H-4),2.76(2H,s,H2-7”'),2.56(2H,t,J＝7.3Hz,H2-7')；13C-NMR(100MHz,CD3OD)δ:101.9(d,C-1),75.1(d,C-2),75.5(d,C-3),71.3(d,C-4),75.1(d,C-5),64.9(t,C-6),131.2(s,C-1'),117.2(d,C-2'),145.9(s C-3'),144.5(s,C-4'),116.2(d,C-5'),121.4(d,C-6'),36.1(t,C-7'),71.9(t,C-8'),126.7(s,C-1”),131.0(d,C-2”,6”),116.6(d,C-3”,5”),160.5(s,C-4”),145.8(d,C-7”),115.2(d,C-8”),168.6(s,C-9”),68.0(s,C-1”'),152.7(d,C-2”',6”'),128.1(d,C-3”',5”'),187.6(s,C-4”'),45.6(t,C-7”'),170.1(s,C-8”')。
Compound 13: brown solid. UV (MeOH) lambdamax(logε):223(4.78),290(3.89)nm；HR-ESI-MS m/z:601.1482[M-H]-(calcd for C31H37O12,601.1487)；1H-NMR(400MHz,CD3OD)δ:7.07(2H,d,J＝10.1Hz,H-2”',6”'),6.76(1H,d,J＝8.1Hz,H-5'),6.73(1H,d,J＝2.0Hz,H-2”),6.69(1H,d,J＝8.0Hz,H-5”),6.65(1H,d,J＝2.0Hz,H-2'),6.61(1H,dd,J＝8.0,2.0Hz,H-6”),6.50(1H,d,J＝8.0,2.0Hz,H-6'),6.12(2H,d,J＝10.1Hz,H-3”',5”'),4.70(1H,dd,J＝9.6,8.0Hz,H-2),4.43(1H,m,H-6a),4.40(1H,d,J＝8.0Hz,H-1),4.23(1H,dd,J＝11.9,5.3Hz,H-6b),3.87(3H,s,-OCH3),3.85(3H,overlap,H-8'a,8”a,8”'a),3.56(1H,t,J＝9.2Hz,H-3),3.43(4H,overlap,H-5,8'b,8”b,8”'b),3.38(1H,overlap,H-4),2.56(2H,s,H2-7”),2.54(2H,t,J＝7.3Hz,H2-7'),1.75(2H,m,H2-7”')；13C-NMR(100MHz,CD3OD)δ:101.9(d,C-1),75.2(d,C-2),75.4(d,C-3),71.4(d,C-4),74.8(d,C-5),64.8(t,C-6),131.3(s,C-1'),117.1(d,C-2'),145.6(s C-3'),144.3(s,C-4'),116.1(d,C-5'),121.7(d,C-6'),36.1(t,C-7'),71.8(t,C-8'),130.8(s,C-1”),117.5(d,C-2”),145.9(s,C-3”),145.1(s,C-4”),116.2(d,C-5”),121.3(d,C-6”),36.3(t,C-7”),72.0(t,C-8”),67.8(s,C-1”'),152.5(d,C-2”',6”'),128.3(d,C-3”',5”'),187.4(s,C-4”'),36.5(t,C-7”'),70.9(t,C-8”'),56.5(q,-OCH3)。
Compound 14: brown solid. UV (MeOH) lambdamax(logε):221(4.85),291(3.77)nm；HR-ESI-MS m/z:615.1657[M-H]-(calcd for C31H35O13,615.1653)；1H-NMR(400MHz,CD3OD)δ:7.08(2H,d,J＝10.2Hz,H-2”',6”'),6.77(1H,d,J＝8.1Hz,H-5'),6.75(1H,d,J＝2.0Hz,H-2”),6.68(1H,d,J＝8.0Hz,H-5”),6.66(1H,d,J＝2.0Hz,H-2'),6.62(1H,dd,J＝8.0,2.0Hz,H-6”),6.51(1H,d,J＝8.0,2.0Hz,H-6'),6.13(2H,d,J＝10.2Hz,H-3”',5”'),4.73(1H,dd,J＝9.6,8.0Hz,H-2),4.42(1H,m,H-6a),4.40(1H,d,J＝8.0Hz,H-1),4.21(1H,dd,J＝11.9,5.3Hz,H-6b),3.87(3H,s,-OCH3),3.85(2H,overlap,H-8'a,8”'a),3.55(1H,t,J＝9.2Hz,H-3),3.43(3H,overlap,H-5,8'b,8”'b),3.38(1H,overlap,H-4),2.54(2H,t,J＝7.3Hz,H2-7'),1.74(2H,m,H2-7”')；13C-NMR(100MHz,CD3OD)δ:101.9(d,C-1),75.1(d,C-2),75.4(d,C-3),71.5(d,C-4),74.8(d,C-5),64.5(t,C-6),131.3(s,C-1'),117.1(d,C-2'),145.6(s C-3'),144.8(s,C-4'),116.2(d,C-5'),121.7(d,C-6'),36.1(t,C-7'),71.8(t,C-8'),131.1(s,C-1”),117.5(d,C-2”),145.9(s,C-3”),145.1(s,C-4”),116.2(d,C-5”),121.3(d,C-6”),169.8(s,C-7”),68.1(s,C-1”'),152.4(d,C-2”',6”'),128.1(d,C-3”',5”'),187.4(s,C-4”'),36.5(t,C-7”'),70.9(t,C-8”'),56.6(q,-OCH3)。
Example 3:
detection of analgesic activity of the compounds of the invention:
the analgesic activity of the extract of the invention is determined by adopting an acetic acid writhing experiment. Half male and female of Kunming mouse, weight 18-22 g, fasting 12 hours before experiment, without water, randomly divided into control group, sample group, positive medicine group, each group has 6. The analgesic effect of the test substance is evaluated by gavage administration at a dose of 200mg/kg, administration of physiological saline with the same amount as that of a negative control group, administration of aspirin with the positive drug group, 40min after administration, intraperitoneal injection of 0.2mL/10g of 0.6% glacial acetic acid solution into each mouse, observation and recording of the writhing times of the mice within 15min after injection of glacial acetic acid for 3-5 min, and calculation of the inhibition rate of the test substance on the acetic acid writhing of the mice according to the following formula.
Pain inhibition (%) is ═ number of writhing in negative control group-number of writhing in administration group)/number of writhing in negative control group × 100%
The activity data are shown in Table 1.
Table 1 analgesic activity data for compounds 1-14 (n ═ 6)
Example 4:
and (3) tablet preparation: 10mg of any one of the compounds obtained in examples 1 and 2, 180mg of lactose, 55mg of starch, 5mg of magnesium stearate;
the preparation method comprises the following steps: the compound, lactose and starch were mixed, uniformly moistened with propylene glycol, the moistened mixture was sieved and dried, and sieved again, magnesium stearate was added, and the mixture was then tabletted to a weight of 250mg per tablet, with a compound content of 10 mg.
Example 5:
an ampoule agent: 5mg of any one of the compounds obtained in examples 1 and 2;
the preparation method comprises the following steps: either of the compounds obtained in examples 1 and 2 was dissolved in 3mL of propylene glycol, and the resulting solution was filtered and aseptically filled in an ampoule.
Example 6:
and (3) capsule preparation: 10mg of any one of the compounds obtained in examples 1 and 2, 187mg of lactose, 3mg of magnesium stearate;
the preparation method comprises the following steps: mixing the compound with adjuvants, sieving, mixing, and encapsulating the obtained mixture into hard gelatin capsules with 200mg of active ingredient content of 10mg in each capsule.
Claims (5)
1. 1-14 of aromatic substituted glucose compounds shown in the following structural formula,
2. the method for producing the compounds 1 to 14 as claimed in claim 1, wherein the aerial parts or whole plant of the plant of camellia [ Ternststoemia gymnanthhera (Wight et Arn.) Bedd ] are dried in the shade, pulverized to 20-30 mesh, extracted with 95% ethanol at room temperature for 2-5 times each for 12-72 hours, the extracts are combined, the extract is concentrated under reduced pressure to obtain an extract, suspended with an appropriate amount of water and distributed with ethyl acetate several times to obtain an ethyl acetate extract, the extract is dissolved with an appropriate amount of chloroform/acetone and then stirred with 80-100 mesh silica gel, and then fractionated by column chromatography on 200-300 mesh silica gel, gradient elution is carried out with 1:0-0:1 chloroform/acetone or 1:0-0:1 chloroform/methanol to obtain 7 main parts, 9:1 chloroform/methanol part, and 7 main parts are obtained, Performing silica gel column chromatography on the chloroform/methanol part at a ratio of 8:2 and the chloroform/methanol part at a ratio of 7:3, performing gradient elution with chloroform/acetone at a ratio of 100:1-1:1 to obtain 10 fractions, and performing repeated silica gel, RP-18 and Sephadex LH-20 column chromatography to obtain compounds 1-14.
3. A pharmaceutical composition comprising a therapeutically effective amount of compounds 1-14 as claimed in claim 1 and a pharmaceutically acceptable carrier.
4. Analgesic agents containing compounds 1 to 14 as claimed in claim 1 and conventional adjuvants.
5. The use of compounds 1 to 14 as claimed in claim 1 for the preparation of an analgesic.
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| Antioxidative Phenolics from the Fresh Leaves of Ternstroemia japonica;Youngmi Jo et al.;《Journal of Natural Products》;20060922;第69卷(第10期);第1399-1403页 * |
| Chemical and biological investigation of some Clerodendrum species cultivated in Egypt;Haytham M. Wahba et al.;《Pharmaceutical Biology》;20100826;第49卷(第1期);第66-72页 * |
| Chemical Constituents from the Roots and Rhizomes of Asarum heterotropoides var. mandshuricum and the In Vitro Anti-Inflammatory Activity;Yu Jing et al.;《Molecules》;20170113;第22卷(第125期);第1-20页 * |
| Haytham M. Wahba et al..Chemical and biological investigation of some Clerodendrum species cultivated in Egypt.《Pharmaceutical Biology》.2010,第49卷(第1期), * |
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