CN102731590A - Coumarin glucoside, preparation method and application of coumarin glucoside - Google Patents
Coumarin glucoside, preparation method and application of coumarin glucoside Download PDFInfo
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- CN102731590A CN102731590A CN2012102423251A CN201210242325A CN102731590A CN 102731590 A CN102731590 A CN 102731590A CN 2012102423251 A CN2012102423251 A CN 2012102423251A CN 201210242325 A CN201210242325 A CN 201210242325A CN 102731590 A CN102731590 A CN 102731590A
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Abstract
The invention discloses coumarin glucoside, a preparation method and an application of the coumarin glucoside. Coumarin glucoside has a structural formula described in formula (I), and the coumarin oumarin glucoside with anti-fouler larva attaching activity and anti-tumour activity, which is described in the formula (I), can be separated and prepared in a boiling tube. The coumarin glucoside can be used for preparing anti-fouler larva attaching drugs and anti-tumour drugs, provides a lead compound for preparing anti-fouler larva attaching drugs and anti-tumour drugs and has wide application prospect. The formula (I) is shown in the description.
Description
Technical field:
The invention belongs to the natural product field, be specifically related to a kind of coumarin glycoside.
Background technology:
1999, belong to the bassoon (Micromelum falcatum) once separating from the Rutaceae Root of Entire Micromelum and obtain tonka bean camphor microf alcatin isovalerate and two hydrogenant cinnamic acid derivatives 3,4-dihydro-1; 2-secomicrominutinin methylester (1); 3,4-dihydro-1,2-secomicrominutinin (2) and 3; 4-dihydro-1,2-secomicrominutinin-9-O-glucoside compounds such as (3).(reference: Kamperdick C, Phuong NM, Sung TV; Schmidt J; Adam G.Cou marins and dihydrocinnamic acid derivatves from Micromeolum falcatum.Phytochemistry, 1999,52:1671-1676).
Summary of the invention:
First purpose of the present invention provides a kind of coumarin glycoside that the biological larva of fouling resistance adheres to active and anti-tumor activity that has.
Coumarin glycoside of the present invention or its salt, its structural formula is shown in formula I:
Formula I.
Second purpose of the present invention provides the preparation method of the coumarin glycoside shown in formula I, it is characterized in that, may further comprise the steps:
(1) with bassoon (Micromelum falcatum) chopping, with ethanol or aqueous ethanolic solution lixiviate, extracting solution concentrates and obtains crude extract;
(2) crude extract is suspended in water, uses ethyl acetate extraction, acetic acid ethyl ester extract is through concentrating after silica gel column chromatography; As elutriant, carry out gradient elution with sherwood oil-acetone from volume ratio 9:1 to 3:7, with the cut point plate of volume ratio 6:4 gradient elution; Carry out thin-layer chromatography; Chloroform-the acetone solvent that with the volume ratio is 8:1 is as developping solution, is that 0.25 ~ 0.35 flow point merges with Rf value, sloughs pigment and obtains the coumarin glycoside that formula I is represented.
Concentrating in step (1) and (2) can adopt conventional method to concentrate, for example concentrating under reduced pressure etc.
Sloughing pigment and can adopt conventional method such as gel chromatographic columns etc. described in the step (2), and be eluting solvent with methyl alcohol.
The present invention finds that through experiment the coumarin glycoside shown in formula I is to the anti-active concentration IC that adheres to of kentrogon
50Be 25.33 μ g/mL; Average half inhibiting rate IC to breast cancer cell F10
50Be 35.8 μ g/mL; Average half inhibiting rate IC to lung carcinoma cell HvEvc
50Be 77.2 μ g/mL.
Therefore, the coumarin glycoside or its salt that provide shown in formula I of the 3rd purpose of the present invention adheres to the application in the medicine the biological larva of preparation fouling resistance.
Described fouling organism larva is preferably kentrogon.
The 4th purpose of the present invention is coumarin glycoside or the application of its salt in the preparation antitumor drug shown in formula I.
Described antitumor drug is preferably anti-breast cancer medicines or anti-lung-cancer medicament.
The 5th purpose of the present invention provides the application of bassoon in the coumarin glycoside of preparation shown in formula I.
The present invention has the coumarin glycoside shown in formula I that the biological larva of fouling resistance adheres to active and anti-tumor activity from separating the bassoon to prepare; It can be used in the biological larva of preparation fouling resistance and adheres to medicine and antitumor drug; The biological larva of fouling resistance adheres to medicine and antitumor drug provides lead compound in order to prepare, and has broad application prospects.
Embodiment:
Following examples are to further specify of the present invention, rather than limitation of the present invention.
Embodiment 1: the preparation of the coumarin glycoside shown in formula I
With 10kg bassoon branch is raw material, and chopping back is with the aqueous ethanolic solution lixiviate of volume(tric)fraction 95% 3 times, and extracting solution is concentrated, merge crude extract.
Be dissolved in the 2000mL water crude extract is outstanding, with ethyl acetate extraction 4 times, combining extraction liquid; Obtain acetic acid ethyl ester extract 113g behind the concentrating under reduced pressure, acetic acid ethyl ester extract is carried out normal pressure silica gel column chromatography (high 1.5m, the glass column of diameter 10cm; Silica gel 200 ~ 300 orders), be elutriant with sherwood oil-acetone solvent system, carry out gradient elution from volume ratio 9:1 to 3:7; Cut point plate with volume ratio 6:4 gradient elution carries out TLC (GF
254) analyze, be that chloroform-acetone solvent system of 8:1 is a developping solution with the volume ratio, with R
fValue is 0.25 ~ 0.35 flow point merging, uses gel Sephadex LH-20 column chromatography again, is the eluting solvent depigmentation with methyl alcohol, obtains compound 1 11.3mg altogether, and outward appearance is a colorless oil.
The structure of compound 1 is identified:
High resolution mass spectrum HR-EIMS m/z466.1829 (C
23H
30O
10 +[M]
+, calculated value: 466.1833). the hydrogen spectrum (
1H-NMR) data and carbon the spectrum (
13C-NMR) data are seen table 1, and these data all are to be interior mark with TMS (TMS), on the NMR of 500MHz and 125MHz, measure respectively, and solvent all is CDCl
3, chemical shift is unit with ppm, coupling constant J, and unit is Hz.UV: 246.0,323.5nm shows to have 7-methyl substituted tonka bean camphor skeleton, infrared IR:3540,1732,1605,1546,1451,1220,1061cm
-1Show and have phenyl ring and hydroxyl.Through 8 tonka bean camphor groups that replace-7 methoxyl groups of the bright existence of a peacekeeping two-dimensional data table in the analytical table 1, an isopentene group and a glucone.The bright H-1 ' of HMBC stave (δ 5.57)/C-2 ' (δ 85.4); H-2 ' (δ 5.18)/C-1 ' (δ 68.0)/C-4 ' (δ 117.0); (δ 4.71 for H-4 '; 4.77)/C-2 '/C-3 ' (δ 143.2)/C-5 ' (δ 17.5) is with H-5 ' (δ 1.65)/C-2 '/C-3 '/C-4 ' is relevant, and the HMBC signal correction of H-1 ' (δ 5.57)/C-7 (162.2)/C-8 (117.1)/C-9 (152.9), proves that the C-1 ' position with an isopentene group side chain links in the C-8 position with the tonka bean camphor group.δ
H3.95 (3H, s) with the HMBC signal correction of C-7 (δ 162.2) proof methyl at C-7, the COSY H-1 "/H-2 " that is correlated with; H-2 "/H-3 "; H-3 "/H-4 ", H-4 "/H-5 ", the relevant H-1 of H-5 "/H-6 " " (δ 4.28)/C-2 ' (δ 85.4); link with H-2 ' (the δ 5.18)/C-1 " (δ 100.9) prove glucosides C-1 " and the C-2 ' of isopentene group side chain with HMBC.HMBC H-6 ' (δ 4.11)/C-1 ' (the δ 68.0)/C-7 ' (δ 18.2) that is correlated with H-7 ' (δ 1.95)/C-6 ' (δ 71.5), proves that first and second bases and the C-1 ' of isopentene group side chain link.Authenticating compound 1 is a coumarin glycoside thus, and its structural formula is shown in formula I, and chemical name is 7-methyl-8-(1-hydroxyethyl-2-O-β-glucopyranosyl-3-methyl-4-butene-1-replacement) tonka bean camphor.
Formula I.
Table 1: the hydrogen spectrum of formula (1) compound 1 and carbon spectrum data
Embodiment 2: the anti-breast cancer activity test of tetrazolium bromide (MTT) method test compounds 1
Collect breast cancer cell F10, inoculate 100 μ L in 96 orifice plates, every porocyte number is approximately 1.0 * 10
5Individual, orifice plate is put into CO
2In the incubator, 37 ℃, 5%CO
2Cultivated 24 hours.Add 10 times of dilutions of ultrapure water, the compound 1100 μ L that embodiment 1 obtains, get 3 parallel, put into CO
2In the incubator, 37 ℃, 5%CO
2Cultivated 24 hours, negative control does not add medicine.Sucking-off nutrient solution again, the MTT50 μ L that every hole adds complete substratum 150 μ L and concentration 2mg/mL cultivates sucking-off liquid after 4 hours, adds DMSO150 μ L, and vibration 10min, ELIASA 490nm measure the result down.Calculate inhibitory rate of cell growth, calculation formula is following: growth inhibition ratio (%)=[(A
Negative-A
Test)/(A
Negative-A
Blank)] * 100%.Utilize the SPSS computed in software again, draw the average half inhibiting rate IC of 1 pair of breast cancer cell of compound that structure representes with formula I
50Be 35.8 μ g/mL, showed obvious activity.
The activity test of the anti-lung cancer of embodiment 3:MTT method test compounds
Collect lung carcinoma cell HvEvc, inoculate 100 μ L in 96 orifice plates, every porocyte number is approximately 1.0 * 10
5Individual, orifice plate is put into CO
2In the incubator, 37 ℃, 5%CO
2Cultivated 24 hours.Add 10 times of dilutions of ultrapure water, the compound 1100 μ L that embodiment 1 obtains, get 3 parallel, put into CO
2In the incubator, 37 ℃, 5%CO
2Cultivated 24 hours, negative control does not add medicine.Sucking-off nutrient solution again, the MTT50 μ L that every hole adds complete substratum 150 μ L and concentration 2mg/mL cultivates sucking-off liquid after 4 hours, adds DMSO150 μ L, and vibration 10min, ELIASA 490nm measure the result down.Calculate inhibitory rate of cell growth according to the method for embodiment 2, utilize the SPSS computed in software again, draw the average half inhibiting rate IC of 1 pair of lung carcinoma cell of compound that structure representes with formula I
50Be 77.2 μ g/mL, showed obvious activity.
Embodiment 4: the biological larva of fouling resistance adhere to activity
Adopt 24 orifice plates to measure the anti-kentrogon that embodiment 1 obtains compound 1 respectively and adhere to activity.
Add the nutrient solution that 1mL contains 10 ~ 15 sophisticated kentrogons in each plate hole, the compound that embodiment 1 is obtained is dissolved in DMSO respectively, is diluted to concentration 100 μ g/mL with the sterilization seawater then, 10 μ g/mL, 1.0 μ g/mL and 0.1 μ g/mL.3 of each concentration are parallel, and do blank with aseptic seawater.Culture plate placed under the room temperature cultivated 24 hours, under anatomical lens, add up the larva number that adheres to, carry out statistical study with the SPSS program.Statistical result showed, compound 1 be at concentration 100 μ g/mL, and 10 μ g/mL when 1.0 μ g/mL and 0.1 μ g/mL, are respectively 18.7%, 37.4%, 58.5%, 61.4% to the average adhesive rate of kentrogon; The blank group is 63.2% to the average adhesive rate of kentrogon.The anti-larva that adheres to the formula computerized compound 1 of inhibiting rate=(blank-adhesive rate)/blank * 100% according to larva adheres to activity, and the anti-larva that draws compound 1 adheres to active concentration IC
50Be 25.33 μ g/mL.This shows that compound 1 of the present invention has the activity of adhering to of the biological larva of fouling resistance, can be used to prepare the biological larva of fouling resistance and adhere to medicine.
Claims (9)
1. the coumarin glycoside shown in the following formula I or its salt:
Formula I.
2. the preparation method of the coumarin glycoside shown in the claim 1 is characterized in that, may further comprise the steps:
(1) with bassoon (Micromelum falcatum) chopping, with ethanol or aqueous ethanolic solution lixiviate, extracting solution concentrates and obtains crude extract;
(2) crude extract is suspended in water, uses ethyl acetate extraction, acetic acid ethyl ester extract is through concentrating after silica gel column chromatography; As elutriant, carry out gradient elution with sherwood oil-acetone from volume ratio 9:1 to 3:7, with the cut point plate of volume ratio 6:4 gradient elution; Carry out thin-layer chromatography; Chloroform-the acetone solvent that with the volume ratio is 8:1 is as developping solution, is that 0.25 ~ 0.35 flow point merges with Rf value, sloughs pigment and obtains the coumarin glycoside that formula I is represented.
3. preparation method according to claim 2 is characterized in that, the simmer down to concentrating under reduced pressure in described step (1) and (2).
4. preparation method according to claim 2 is characterized in that, the pigment of sloughing described in the step (2) is through gel filtration chromatography, is that eluent is sloughed pigment with methyl alcohol.
5. described coumarin glycoside or its salt of claim 1 adheres to the application in the medicine the biological larva of preparation fouling resistance.
6. application according to claim 5 is characterized in that, described fouling organism larva is a kentrogon.
7. described coumarin glycoside or the application of its salt in the preparation antitumor drug of claim 1.
8. application according to claim 7 is characterized in that, described antitumor drug is anti-breast cancer medicines or anti-lung-cancer medicament.
9. the application of bassoon in the described coumarin glycoside of preparation claim 1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105801638A (en) * | 2016-04-26 | 2016-07-27 | 黑龙江中医药大学 | Compound 4(S)-4,5-dihydroxy-alpha-tetralone 4-O-beta-D-glucopyranose (1->6)-beta-D-glucopyranoside, and preparation method and application thereof |
| CN105801637A (en) * | 2016-04-26 | 2016-07-27 | 黑龙江中医药大学 | Compound 4(S)-4,5-dihydroxy-alpha-tetralone 5-O-beta-D-glucopyranose (1->6)-beta-D-glucopyranoside, and preparation method and application thereof |
Citations (1)
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| CN101318981A (en) * | 2008-07-17 | 2008-12-10 | 中国科学院南海海洋研究所 | Method for separating benzoxazole oxazinone glycoside compounds from acanthus |
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2012
- 2012-07-12 CN CN2012102423251A patent/CN102731590A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101318981A (en) * | 2008-07-17 | 2008-12-10 | 中国科学院南海海洋研究所 | Method for separating benzoxazole oxazinone glycoside compounds from acanthus |
Non-Patent Citations (2)
| Title |
|---|
| XIONGMING LUO ET AL.: "Two New Coumarins from Micromelum falcatum with Cytotoxicity and Brine Shrimp Larvae Toxicity", 《MOLECULES》 * |
| 黄升等: "小芸木属植物化学成分及药理活性研究进展", 《中药材》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105801638A (en) * | 2016-04-26 | 2016-07-27 | 黑龙江中医药大学 | Compound 4(S)-4,5-dihydroxy-alpha-tetralone 4-O-beta-D-glucopyranose (1->6)-beta-D-glucopyranoside, and preparation method and application thereof |
| CN105801637A (en) * | 2016-04-26 | 2016-07-27 | 黑龙江中医药大学 | Compound 4(S)-4,5-dihydroxy-alpha-tetralone 5-O-beta-D-glucopyranose (1->6)-beta-D-glucopyranoside, and preparation method and application thereof |
| CN105801637B (en) * | 2016-04-26 | 2018-05-11 | 黑龙江中医药大学 | Compound 4 (S) -4,5- dihydroxy-α-tetralone 5-O- β-D- glucopyranoses (1 → 6)-β-D- glucopyranosides and preparation method and application |
| CN105801638B (en) * | 2016-04-26 | 2018-09-18 | 黑龙江中医药大学 | Compound 4 (S) -4,5- dihydroxy-α-tetralone 4-O- β-D- glucopyranoses (1 → 6)-β-D- glucopyranosides and the preparation method and application thereof |
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Inventor after: Luo Xiongming Inventor after: Yin Hao Inventor after: Li Chuanrong Inventor after: Li Qingxin Inventor before: Luo Xiongming Inventor before: Zhang Cai Inventor before: Yin Hao Inventor before: Li Chuanrong Inventor before: Li Qingxin |
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Free format text: CORRECT: INVENTOR; FROM: LUO XIONGMING ZHANG SI YIN HAO LI CHUANRONG LI QINGXIN TO: LUO XIONGMING YIN HAO LI CHUANRONG LI QINGXIN |
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Application publication date: 20121017 |