CN1027371C - Synthetic process of diterpenic lactone - Google Patents
Synthetic process of diterpenic lactone Download PDFInfo
- Publication number
- CN1027371C CN1027371C CN 89106941 CN89106941A CN1027371C CN 1027371 C CN1027371 C CN 1027371C CN 89106941 CN89106941 CN 89106941 CN 89106941 A CN89106941 A CN 89106941A CN 1027371 C CN1027371 C CN 1027371C
- Authority
- CN
- China
- Prior art keywords
- compound
- triptolide
- group
- synthetic
- diterpenic lactone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The present invention relates to a method for artificially synthesizing a diterpene lactone compound with a structural formula disclosed in the specification, wherein R<1> is a halogen element, a hydroxy group, a methoxy group and a propylthio group; R<2> is a hydroxy group and an acetyl group. The present invention is characterized in that when the diterpene lactone compound is synthesized, a compound of which the R<1> is H reacts with triptolide; then the product reacts with acetic anhydride. The compound has the functions of inflammation resistance and immunological suppression.
Description
The present invention relates to have the synthetic method of the new diterpenic lactone of anti-inflammatory and immunosuppressive action.
Known in the state of the art, Chinese medicine trypterygine (tripterygium Wilfordii) mainly is distributed in provinces such as Chinese Fujian, Zhejiang, Jiangxi, Anhui, Hunan, Taiwan, and its root can be used for treating rheumatic arthritis.Particularly from velamen of Tripterygium wilfordii, separate obtaining triptolide (Triptolide), have antitumor action [J.Amer.Chem.Sco., the 94th volume, the 7194th page (1972)] as known diterpenic lactone.The present inventor opens an epoxy in three epoxies of triptolide under certain condition; and further the resultant acetylize has been synthesized new diterpenic lactone; prove that through pharmacological testing this compounds has good anti-inflammatory and immunosuppressive action.
The triptolide (Triptolide) that the objective of the invention is to obtain with separation in the velamen of Tripterygium wilfordii is as the raw material for preparing new diterpenic lactone, pass through chemical process, open 11 of triptolide with different reagent, 12-epoxy and obtain the derivative of a series of triptolides, these compounds have anti-inflammatory and suppress immunization.
Compound of the present invention is represented with following structural formula:
Wherein, R
1=halogen, hydroxyl, methoxyl group and rosickyite base; R
2=hydrogen and ethanoyl.When synthetic following formula compound, with R
1=H compound and triptolide (Triptolide, II) one reacts,
Obtain R
2The following formula compound of=H; Further its resultant and Glacial acetic acid reaction are generated R
2The above-mentioned diterpenic lactone of=ethanoyl.
Among the present invention, halogen atom is fluorine, chlorine, bromine, iodine.With R
1The compound of-H is an example, has enumerated hydrogenchloride, hydrogen bromide, hydrogen halide such as hydrogen iodide, and methyl alcohol, propylmercaptan etc.The reaction conditions of each compound is not quite similar among preparation the present invention, but generally all is to finish under comparatively gentle condition.Temperature of reaction also easily control, as refrigerator 2-3 ℃, room temperature and＜70 ℃ carry out, condition is more easy to control.Agents useful for same also is a common agents, as ether, and methyl alcohol, acetone, methylene dichloride etc.Reaction times has long (two weeks) that short (20-30 minute) arranged.See each examples of compounds of preparation for details.
The derivative of respectively organizing with method synthetic above-claimed cpd of the present invention all has anti-inflammatory and immunosuppressive action.Describe the synthetic method of The compounds of this invention below in detail, but do not limit the present invention.Wherein
Example 1a:R
1=Cl, R
2=H,
Example 2b:R
1=Br, R
2=H,
Example 3c:R
1=-OCH
3, R
2=H,
Example 4d:R
1=OH, R
2=H,
Example 5e:R
1=-SCH
2CH
2CH
3, R
2=H,
Example 6f:R
1=Cl, R
2=COCH
3
Embodiment 1
[a's is synthetic] adds hydrochloric acid-Glacial acetic acid (36% hydrochloric acid of 0.35ml is dissolved in the 1ml Glacial acetic acid) of 1ml 0.4N in the 20mg triptolide, add a cover in refrigerator (3-4 ℃) and placed 16-18 hour.The water that adds 5 times of amounts in reaction solution, the adularescent precipitation generates, and uses ether extraction 3 times.Combined ether layer washes with water to neutrality, uses anhydrous sodium sulfate drying.Cross and filter to remove anhydrous sodium sulphate, the volatilization ether.Residue separates with silica gel thin-layer chromatography that (developping agent: 2% methyl alcohol/chloroform), collect the component that contains a, with 5% methyl alcohol/chloroform wash-out, the resulting thick component that contains a obtains the white, needle-shaped crystals of 18mga with the chloroform recrystallization.Yield is 82%.
Also proved the structure of this compound with x-line single crystal diffraction method.
m.p.256-258℃
MSm/z（%）;
396（M
+，0.88），378（0.42），361（1.88），
343（34.91），273（17.06），247（39.04），
229（17.33），149（26），121（23），105（32），
71（100）
KBr
IR γmax cm
-1
The 3530(hydroxyl),
1751,1673(α, β-unsaturated γ-lactones)
1H-NMR（400MHz，CDCl
3）δ（ppm）;
0.89（3H，d，J＝6.97Hz，C
16-3H），
1.00（3H，J＝6.60Hz，C
17-3H）
1.12（3H，s，C
20-3H），1.27，1.61（2H，C
1-2H），
1.98（1H，t，C
6-βH），2.17，2.32（2H，C
2-2H），
2.20（1H，m，C
6-αH），2.56（1H，sept，C
15-H），
2.75（1H，m，C
5-H），
3.12（1H，d，J＝1.46Hz，C
14-H），
3.45（1H，d，J＝5.86Hz，C
7-H），
3.90（1H，d，J＝5.13Hz，C
11-H），
4.26（1H，dd，J＝5.13，1.46Hz，C
12-H），
4.74（2H，m，C
19-2H）
13C-NMR（400MHz，DMSO）δ（ppm）;
13.27（q，C
20），15.17（q，C
16），
15.38（q，C
17），17.01（t，C
2），
23.26（t，C
16），28.98（d，C
15），
30.41（d，C
1），35.74（s，C
10），
39.88（d，C
5），57.66（d，C
11），
59.08（d，C
12），61.31（d，C
7），
70.74（t，C
19），76.24（d，C
14），
125.27（s，C
3），161.20（s，C
4），
174.19（s，C
18），
60.51，70.20，76.58（C
8，C
9，C
13）
Embodiment 2[b's is synthetic]
The 20mg triptolide is dissolved in the 15ml acetone, refluxes 25 minutes behind the dense hydrogen bromide of adding 1ml water and 0.5ml.Add 30ml water after the reaction, a part of acetone is removed in decompression, and with 15ml dichloromethane extraction 3 times, with the anhydrous magnesium sulfate drying dichloromethane layer, decompression volatilization methylene dichloride, residue obtain the plate crystal of 18mg b after with methylene dichloride-sherwood oil recrystallization.Yield is 75%.
Silica gel thin-layer chromatography condition: 95 parts of chloroforms: 5 parts of methyl alcohol.
m.p.230～232℃，R
f＝0.64
Ultimate analysis;
Calculated value (%); C54.55, H5.68, Br17.95
Measured value (%); C54.25, H5.79, Br18.93
MSm/z（%）361（M
+-Br，3），
343（M
+-Br-H
2O，14），325（5），271（9），
241（9），189（18），167（23），151（27），
137（84），43（100）
H-NMR（400MHz），CDCl
3）δ（ppm）;
0.88（3H，d，J＝7Hz，C
16-3H），
0.98（3H，d，J＝7Hz，C
17-3H），
1.11（3H，s，C
20-3H），1.22（1H，m），
1.61（1H，q，J＝4.12Hz），2.00（1H，m），
2.15（1H，m），2.33（1H，m），2.62（2H，m），
3.14（1H，s，C
14-H），
3.38（1H，d，J＝6Hz，C
7-H），
3.84（1H，d，J＝4Hz，C
11-H），
4.14（1H，d，J＝4Hz，C
12-H），
4.68（2H，br，s，C
19-2H）
Kedd ' s developer: red-purple.
Embodiment 3[C's is synthetic]
Adding 150 μ l anhydrous methanols and stirring 20 minutes in 2g neutral alumina (400 ℃ place 3 hours).With being added in the aluminum oxide of front behind the 40ml anhydrous methylene chloride dissolving 30mg triptolide, room temperature was placed 10 hours, stirred down to add the 1ml anhydrous methanol, and room temperature placed for 1 week.Filtering reacting liquid is used the methanol-eluted fractions aluminum oxide, merges methanol solution, the volatilization methanol solution.Silicagel column separates (developping agent is a chloroform) on the residue, and (20ml/ component) isolates object from the 5th component.With the needle crystal that obtains 3mgC behind methylene dichloride-sherwood oil recrystallization.Yield is 10%.
The silica gel thin-layer chromatography condition is: 95 parts of chloroforms: 5 parts of methyl alcohol.
m.p.272-274℃，R
f＝0.75
Kedd ' s developer, red-purple (spot)
High resolution mass spectrum
Molecular weight 392.1837
Molecular formula: C
21H
28O
7MSm/z(%);
392（M
+，100），377（M
+-CH
3，43.89），
271（1.5），
1H-NMR（400MHz，CDCl
3）δ（ppm）;
0.90（3H，d，J＝7Hz，C
16-3H），
1.06（3H，J＝7Hz，C
17-3H），
1.17（3H，s，C
20-3H），
1.58（1H，q，J＝5.12Hz），1.9（1H，m），
2.10（1H，m），2.22（2H，m），2.35（1H，m），
2.91（1H，m），3.44（3H，s，OCH
3），
3.53（1H，d，J＝3Hz，C
11-H），
3.63（1H，br，s，C
14-H），
4.34（1H，d，J＝3Hz，C
12-H），
4.71（2H，br，s，C
19-2H），
Embodiment 4[d's is synthetic]
The 20mg triptolide is dissolved in the 10ml methyl alcohol, and adds 5ml distilled water, 5ml phosphoric acid buffer (pH7.4) and 200 μ l NHEt
2, placed for 1 week after the stirring at room.Reaction solution adds the dilution of 20ml water with the neutralization of 2N sulfuric acid, uses 10ml chloroform extraction 4 times.Extracting solution with anhydrous magnesium sulfate drying after, volatilization, the residual silicagel column that heats up in a steamer on the thing separates (developping agent: 1% methyl alcohol/chlorine is visited), isolates object (20ml component) from the 6th component.Acetone recrystallization obtains the white powder of 16mg d.Yield is 76%.
Silica gel thin-layer chromatography condition: 95 parts of chloroforms: 5 parts of methyl alcohol.
R
f＝0.50 m.p.180-182℃
Kedd ' s developer: red-purple (spot).
MSm/z（%）;361（M
++1-H
2O，2），
342（M
+-2H
2O，3），317（5），259（7），
231（9），193（7），151（12），71（31），43（100），
1H-NMR（400MHz，CDCl
3）δ（ppm）;
0.69（3H，d，J＝7Hz，C
16-3H），
0.92（3H，d，C
20-3H），
0.94（3H，d，J＝7Hz，C
17-3H），1.24（1H，m），
1.38（1H，q，J＝4.12Hz），2.13（1H，m），
2.28（2H，m），2.85（1H，m），
3.46（1H，d，J＝2Hz，C
11-H），
3.56（1H，d，J＝6Hz，C
7-H），
4.31（1H，d，J＝2Hz，C
12-H），
4.76（2H，m，C
19-2H），
Embodiment 5[e's is synthetic]
The 30mg triptolide is dissolved in the 3.5ml methyl alcohol, adds 3.5ml phosphoric acid buffer (pH7.4) and 400 μ l propylmercaptans, places for 2 weeks after the stirring at room, adds 20ml water dilute reaction solution, 10ml dichloromethane extraction 4 times.Extracting solution volatilizees after with anhydrous magnesium sulfate drying, and silicagel column separates (developping agent: 1% methyl alcohol/chloroform), isolate object from the 3rd component (25ml/ component) on the residue.Obtain the needle crystal of 22mg e with methylene dichloride-sherwood oil recrystallization.Yield is 61%.
Silica gel thin-layer chromatography condition: 96 parts of chloroforms: 5 parts of methyl alcohol.
R
f＝0.40 m.p.240-242℃
Kedd ' s developer: red-purple (spot).
Ultimate analysis shows and contains sulphur.
KBr
IR γmax cm
-1
The 3450(hydroxyl),
1750,1680(α, β-unsaturated γ-lactones)
MSm/z（%）;
437（M
++1，7），436（M
+，2），389（5），343（7），
315（63），273（9），160（26），71（29），
43（100）
1H-NMR（500MHz，DMSO-d
6）δ（ppm）;
0.75（3H，d，J＝6Hz，C
16-3H），
0.92（3H，d，J＝6Hz，C
17-3H）
0.94（3H，s，C
20-3H），
0.98（3H，t，J＝6Hz，CH
3CH
2CH
2S-），
1.27（1H，m，C
1-αH），
1.41（1H，q，J＝5，12Hz，C
1-βH），
1.60（2H，m，CH
3CH
2CH
2S-），
1.82（1H，q，J＝13，15Hz，C
6-βH），
1.98（1H，m，C
2-βH），2.13（1H，m，C
2-αH），
1.17（1H，m，C
6-αH），2.21（1H，m，C
15-H），
2.65（2H，m，-CH
2-S-），2.7（1H，m），
2.87（1H，d，J＝8.5Hz），
3.16（1H，d，J＝5Hz，C
12-H），
3.34（1H，d，J＝6Hz，C
17-H），
3.73（1H，d，J＝5Hz，C
11-H），
4.83（2H，m，C
19-2H），
Embodiment 6[f's is synthetic]
The a of 20mg is dissolved in the 1ml pyridine, places a week behind the adding 1ml Glacial acetic acid.Reaction solution is poured in the 20ml frozen water, uses 15ml dichloromethane extraction 3 times.The combined dichloromethane layer is used the 10ml water elution, volatilizees behind the anhydrous magnesium sulfate drying, and (developping agent: 2% methyl alcohol/chloroform) (15ml/ component) isolates object from the 3rd component in the silicagel column separation on the residue.Obtain the plate crystal of 18mgf with methylene dichloride-sherwood oil recrystallization.Yield is 61%.
The silica gel thin-layer chromatography condition is: 95 parts of chloroforms: 5 parts of methyl alcohol.
R
f＝0.55 m.p.194-196℃
Proved this structural formula with x-line single crystal diffraction method.
Kedd ' s developer: red-purple (spot)
MSm/z（%）;
493（M
++1，3），395（M
+-COCH
3，3），343（16），
247（23），151（14），71（30），43（100）
1H-NMR（400MHz，CDCl）δ（ppm）;
0.91（3H，d，J＝7Hz，C
16-3H），
1.03（3H，d，J＝7Hz，C
17-3H），
1.07（3H，s，C
20-3H），1.27（1H，m），1.64（1H，m），
1.98（1H，t，J＝13Hz），2.14（3H，s，-COCH
3），
2.23（1H，m），2.35（1H，m），
2.75（1H，m，C
5-H），
3.50（1H，d，J＝6Hz，C
7-H），
3.80（1H，d，J＝4Hz，C
11-H），
4.12（1H，d，J＝4Hz，C
12-H），
4.68（2H，m，C
19-2H），
Embodiment 7
Pharmacology result:
Prove that through generate test and lymphocyte transformation test with hemolytic antibody good anti-inflammatory and immunosuppressive action are arranged with the inventive method institute synthetic diterpenic lactone.The result is as follows:
1. diterpenic lactone restraining effect that mouse spleen lymphocyte is transformed:
Get 18-22 gram C
57Male mice is got spleen under aseptic technique, after shredding, splenocyte is suspended from the HanK ' s liquid, washes cell 3 times, is made into 7 * 10 with RPMI-1640 again
6The cell suspension of splenocyte/ml adds this cell suspension in 96 orifice plates, every hole 50 μ l, except that blank, all the other each Kong Jun add ConA50 μ l(0.125 μ g), dosing holes also adds specimen 50ml except that ConA.Each Kong Jun supplies final volume to 200 μ l with RPMI-1640, and each specimen all has contrast separately and stimulates contrast (being ConA), and each group all has 4 parallel holes.96 orifice plates are placed 37 ℃ of CO
2Incubator was cultivated 48 hours, took out every hole and added
3H-TdR20 μ l(0.3 μ ci) continues to cultivate 6 hours.Take out the back collecting cell on glass fibre membrane.Dry for 80 ℃, put diaphragm and in the toluene scintillation solution, count, with
3The radioactivity relative populations CPM that H-TdR mixes DNA represents the height of lymphocyte transformation rate, calculates specimen to LT inhibiting rate.(table is seen the literary composition back)
Inhibiting rate (%)=(stimulating contrast CMP-specimen CPM)/(stimulating contrast CPM) * 100
2. diterpenic lactone is to the influence of mouse hemolytic antibody generation
Get 20-24 gram Kunming mouse, abdominal injection sheep red blood corpuscle (SRBC) 0.2ml(2 * 10
9SRBC/ml), random packet after 4 hours, control group i.p. physiological saline, each administration group is i.p. specimen solution according to dosage, once a day, and totally four days, plucked eyeball on the 5th day in immunity and get blood, separation of serum adds SRBC and guinea pig serum with dilute serum, place 37 ℃, 10 minutes, promptly produce haemolysis, get supernatant, add Dou Shi liquid and promptly be reddish-brown, in the 540nm colorimetric, surveying SRBC HD50 O.D.(simultaneously promptly partly measures SRBC and adds Dou Shi liquid), calculate half hemolysis value HC
50, with HC
50The height of value is represented the level of hemolytic antibody content in the serum.
Sample HC
50=(sample O.D.)/(O.D. of SRBC HD50) * serum diluting multiple
Group dosage HC
50Inhibiting rate (%)
（mg/kg）
Contrast 32.8 ± 8.0
Endoxan 10 4.1 ± 1.1 91.9**
Synthetics c 0.1 11.7 ± 2.6 64.3**
f 0.1 15.3±3.0 53.3＊＊
b 0.1 5.4±1.2 83.6＊＊
a 0.1 6.8±1.4 79.4＊＊
＊：P＜0.05 ＊＊：P＜0.001
The inhibiting rate (%) of group drug level CMP(X ± SE)
Blank 1061.0 ± 238.8
Stimulate contrast 47197.7 ± 5039.5
Compound C 1 * 10
-548223.0 ± 3956.1-2.2
1×10
-457626.8±7145.9 -22.0
1×10
-316364.3±1835.3＊ 65.3
1×10
-2904.8±244.8＊＊ 98.1
1×10
-1487.3±109.1＊＊ 99.0
Blank 1218.5 ± 139.0
Stimulate contrast 41997.5 ± 4664.7
Compound f 1 * 10
-56011.5 ± 277.6** 85.7
1×10
-4629.5±141.6＊＊ 98.5
1×10
-3606.0±136.9＊＊ 98.6
1×10
-2345.5±103.1＊＊ 99.1
1×10
-1221.0±53.9＊＊ 99.5
Blank 889.3 ± 60.7
Stimulate contrast 24106.0 ± 4596.9
Compound b 1 * 10
-12413.0 ± 172.0* 98.3
1×10
-10397.8±43.6＊ 98.3
1×10
-8282.8±30.5＊ 98.8
1×10
-6182.3±50.8＊ 99.2
Blank 787.5 ± 126.5
Stimulate contrast 24011.3 ± 2525.5
Compound a 1 * 10
-121781.5 ± 326.9** 92.6
1×10
-1021747.3±3723.2 9.4
1×10
-87545.3±1806.4＊ 68.6
1×10
-61642.3±618.2＊＊ 93.2
＊：P＜0.01 ＊＊：P＜0.001
Claims (1)
1, the preparation method of a kind of diterpenic lactone of representing with following structural formula (I),
Wherein, R
1=halogen, hydroxyl, methoxyl group or rosickyite base; R
2=hydrogen or ethanoyl is characterized in that using R when synthetic described diterpenic lactone (I)
1The compound of-H and triptolide (Triptolide, II) one reacts,
R in described diterpenic lactone (I)
2During=ethanoyl, using R
1After the compound of-H and triptolide (II) reaction, with its resultant and Glacial acetic acid reaction.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89106941 CN1027371C (en) | 1989-09-08 | 1989-09-08 | Synthetic process of diterpenic lactone |
| JP21360890A JPH03178977A (en) | 1989-09-08 | 1990-08-10 | Diterpene lactone compound and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89106941 CN1027371C (en) | 1989-09-08 | 1989-09-08 | Synthetic process of diterpenic lactone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1050021A CN1050021A (en) | 1991-03-20 |
| CN1027371C true CN1027371C (en) | 1995-01-11 |
Family
ID=4856988
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 89106941 Expired - Fee Related CN1027371C (en) | 1989-09-08 | 1989-09-08 | Synthetic process of diterpenic lactone |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPH03178977A (en) |
| CN (1) | CN1027371C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100398544C (en) * | 2002-09-18 | 2008-07-02 | 成都达远药物有限公司 | Aqueous triptolide alcohol derivative with high immunesuppressive activity and its application |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843452A (en) * | 1992-11-09 | 1998-12-01 | Pharmagenesis, Inc. | Immunotherapy composition and method |
| US5759550A (en) * | 1993-05-06 | 1998-06-02 | Pharmagenesis, Inc. | Method for suppressing xenograft rejection |
| US5663335A (en) * | 1996-03-01 | 1997-09-02 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| US5962516A (en) * | 1997-02-28 | 1999-10-05 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| JP2002523495A (en) * | 1998-09-02 | 2002-07-30 | ファーマジェネシス， インコーポレイテッド | Triptolide prodrug with high water solubility |
| EP1375488B1 (en) * | 1998-09-02 | 2006-08-02 | Pharmagenesis, Inc. | Triptolide prodrugs having high aqueous solubility |
| JP4680589B2 (en) | 2002-05-31 | 2011-05-11 | ファーマジェネシス， インコーポレイテッド | Triptolide derivatives for the regulation of apoptosis and immunosuppression |
| CA2508217A1 (en) * | 2002-12-17 | 2004-07-15 | Pharmagenesis, Inc. | Triptolide derivatives as immunomodulators and anticancer agents |
| US6943259B2 (en) * | 2003-02-25 | 2005-09-13 | Pharmagenesis, Inc. | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| WO2005062913A2 (en) | 2003-12-24 | 2005-07-14 | Pharmagenesis, Inc. | Triplide 5,6-derivatives as immunomodulators and anticancer agents |
| EP1722806A4 (en) | 2004-02-09 | 2009-09-16 | Pharmagenesis Inc | Methods for isolation of triptolide compounds from tripterygium wilfordii |
| EP1732536B1 (en) | 2004-03-02 | 2012-04-25 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| WO2006044496A2 (en) | 2004-10-13 | 2006-04-27 | Pharmagenesis, Inc. | Identification and screening of triptolide target molecules |
| CA2750844A1 (en) * | 2009-02-05 | 2010-08-12 | Pharmagenesis, Inc. | Triptolide c-ring derivatives as anticancer agents and immune modulators |
| CN106883284B (en) * | 2017-03-03 | 2018-10-16 | 广东省中医院 | The fast and safely preparation method of Triptolide triol |
-
1989
- 1989-09-08 CN CN 89106941 patent/CN1027371C/en not_active Expired - Fee Related
-
1990
- 1990-08-10 JP JP21360890A patent/JPH03178977A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100398544C (en) * | 2002-09-18 | 2008-07-02 | 成都达远药物有限公司 | Aqueous triptolide alcohol derivative with high immunesuppressive activity and its application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1050021A (en) | 1991-03-20 |
| JPH03178977A (en) | 1991-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1027371C (en) | Synthetic process of diterpenic lactone | |
| CN1028104C (en) | Carbostyril derivatives | |
| CN1037439C (en) | Neuroprotective indolone and related derivatives | |
| CN1154488C (en) | Immuno inhibitort | |
| CN1309399C (en) | Compound 'Shuanghuanglian' preparation and preparing process thereof | |
| CN1223595C (en) | Triptolide alcohol derivative and its use | |
| CN1084177A (en) | 2 of the antiviral and antitumour activity of tool '-deoxidation-2 ', 2 '-difluoro (4-substituted pyrimidines) nucleosides and intermediate | |
| CN1990484A (en) | Silybin esters derivatives and preparation and use thereof | |
| CN86104664A (en) | The hero-1 that replaces, 4-diene-3, the method for making of 17-cyclohexadione compounds | |
| CN1212966A (en) | Usage of steroi saponin for preventing and curing senile dementia and new steroid saponin | |
| CN1680358A (en) | Composition concerned with isoflavone and the similar and therapeutical method | |
| CN1039910C (en) | Calanthamine derivatives, a process for their preparation and their use as medicaments | |
| CN1108658A (en) | Galanthamine derivatives, a process for their preparation and their use as medicaments | |
| CN1029968C (en) | Process for preparation of N-heteroaryl-purin-6-amines and their use as medicaments | |
| CN1990482A (en) | Flavanonol compounds and their production method and use | |
| CN1126723A (en) | Preparation of derivative of 4-deoxcide-4-surface-podocyllin poison | |
| CN1024197C (en) | Acylated derivatives of etoposide | |
| CN1159337C (en) | Steroides sulfatase inhibitors and methods for making and using same | |
| CN1147297C (en) | Novel aesculetin derivatives and pharmaceutical | |
| CN87104750A (en) | 6 or 7-methylene radical androstane-1,4-diene-3, the preparation method of 17-diketone novel derivative | |
| CN1159806A (en) | Imidazopyridine-pyrrolidone and imidazopyridine-oxaolidone | |
| CN1033056A (en) | Saliva acylglyceride and preparation method thereof | |
| CN1594341A (en) | Fatty acid ester compounds of ginsenoside secondary glycoside compound K and method for preparing same | |
| CN101077341A (en) | Application of aurantio-obtusifolin or its derivates in preparing hypolipidemic drug | |
| CN1656100A (en) | Camptothecins with a modified lactone ring |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |