CN1052859A - The structure of 17-hydroxyl triptolide alcohol and analogue and preparation method - Google Patents
The structure of 17-hydroxyl triptolide alcohol and analogue and preparation method Download PDFInfo
- Publication number
- CN1052859A CN1052859A CN 89105432 CN89105432A CN1052859A CN 1052859 A CN1052859 A CN 1052859A CN 89105432 CN89105432 CN 89105432 CN 89105432 A CN89105432 A CN 89105432A CN 1052859 A CN1052859 A CN 1052859A
- Authority
- CN
- China
- Prior art keywords
- product
- chloroform
- add
- alcohol
- gets
- 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.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides have anti-inflammatory, compound 17-hydroxyl triptolide alcohol and the chemical structure of analogue and their preparation method of immunosuppression, antitumor and antifertility effect.Its main technique is: directly extract with organic solvent extraction or ethanol after getting tripterygium leaf or root poach, carry out chromatographic separation again, concentrate, crystallization, get final product 17-hydroxyl triptolide alcohol, this compound further carries out building-up reactions, can obtain 17 hydroxyl triptolide alcohol analogues respectively.
Description
The present invention relates to the chemical structure and the preparation method of 17-hydroxyl triptolide alcohol and analogue thereof.
Known in the state of the art, the root of Chinese medicine trypterygine (Tripterygium Wilfordii Hook.f.) can be used for treating rheumatoid arthritis, and its preparation " Tripterysium Glucosides " (containing 17-hydroxyl triptolide alcohol) has tangible anti-inflammatory, immunosuppression and antifertility action.With regard to antifertility, with 1/4～1/3 of rheumatoid arthritis treatment amount, the clinical apparent side effect of not finding, experimentation on animals there is no pathological change under light microscopic, Electronic Speculum, about 200 examples of retrospective study, fertility can both be recovered after the drug withdrawal.Isolated diterpene triptolide alcohol (triptolide) has obvious antineoplastic from trypterygine.Existing male antifertility medicine gossypol has certain toxic side effect, and under antifertility dosage, all the pill taker can cause that all blood potassium reduces, and wherein 1～10% in the half a year of taking medicine hypokalemia and paralysis can take place; 1/4 pill taker's fertility is changed into irreversible; Can cause 30% pill taker tubular injury in various degree.
The objective of the invention is from trypterygine to separate the compound that makes new advances, have anti-inflammatory, immunosuppression, antitumor and antifertility action, determine its chemical structure and preparation method.
Compound provided by the present invention is that the chemical structure of 17-hydroxyl triptolide alcohol (17-Hydroxytriptolide) and analogue thereof is represented with following structural formula:
Wherein～R
1=-F ,-Cl ,-Br ,-I ,-OH or-OCH
3
R
2=F, Cl or OH;
R
3=CH
2F, CH
2Cl, CH
2Br, CH
2I, CH
2OH, CH
2OCH
3, CHO, COOH, CH
2OCOCH
3, COOCH
2CH
3Or COOCH
3
(～R
1, R
2=... O ... can think that 12,13 is α type epoxy group(ing))
(～R
1, R
2=... O ..., R
3=CH
2Be 17-hydroxyl triptolide alcohol during OH, all the other are its analogue).
The method for preparing above compound is as follows: getting trypterygine, some (content of tripterygium leaf is higher, so it is some then better only to get tripterygium leaf, but root, Pi Yike), after poach removes slag, extract or ethanol directly extracts with organic solvent or compounded organic solvent, the gained sample liquid is carried out chromatography, carry out wash-out with organic solvent or compounded organic solvent then, collection contains the effluent liquid of 17-hydroxyl triptolide alcohol, concentrates post crystallization, can obtain 17-hydroxyl triptolide alcohol (～R
1, R
2=... O R
3=CH
2OH).This compound is further carried out building-up reactions can obtain 17-hydroxyl triptolide alcohol analogue respectively.Above-mentioned said building-up reactions refers to; 17 functional groups are oxidized to aldehyde or acid; 17 hydroxy halogenos become X; 17 hydroxyls and diazomethane generate ether; 17 hydroxyls and H-R ' generation ester; 17 functional groups be behind the carboxyl again with H-R ' generation ester; With 17 hydroxyl triptolide alcohols, above-mentioned aldehyde, 17 halides, ether and esters separately respectively with H-R or BF
3The reaction of-etherate (R=F, Cl, Br, I, OH, OCH
3; X=F, Cl, Br, I; R '=CH
3COO, CH
3CH
2, CH3O).More than said organic solvent or compounded organic solvent mainly be meant: chloroform, methyl alcohol, methyl alcohol-benzene, ethyl acetate-sherwood oil, ethanol-chloroform, methyl alcohol-chloroform, acetone-chloroform, hexanaphthene-acetone, acetone-benzene etc.Chromatography column can adopt silicagel column or neutral alumina post.
17-hydroxyl triptolide alcohol physico-chemical property is as follows:
mp.232-233.5℃
MS m/z（%） 376（M
+，0.90），358（2.71），345（1.38）317（7.79），311（9.14），271（21.59），151（57.92），43（75.00），41（100.00），31（63.77）.
13C-NMR，12.37（q，C
16），13.64（q，C
20），16.55（t，C
2）22.60（t，C
6），28.96（t，C
1），35.17（s，C
10）35.72（d，C
15）39.93（d，C
5），54.46（d，C
12），55.23（d，C
11），59.70（d，C
7）60.73（s），61.59（t，C
17），62.90（s），64.34（s），70.12（t，C
19）71.56（d，C
14），123.02（s，C
3），162.32（s，C
4），173.05（s，C
18）
1H-NMR 0.84（3H，d，C
16-H
3），0.96（3H，s，C
20-H
3），1.30（2H，m，C
1-H
2），1.97，2.10（2H，m，C
2-H
2），1.82，2.18（2H，m，C
6-H
2），2.11（1H，m，C
15-H），2.59（1H，m，C
5-H）3.15，3.28（2H，m，C
17-H
2），3.34（1H，s，C
14-H），3.36（1H，d，C
7-H），3.65（1H，d，C
12-H），3.90（1H，d，C
11-H），4.60（1H，C
14-OH），4.81（2H，q，C
19-H
2）
X-line single crystal diffraction has also proved the structure of this compound.
Above compound proves to have anti-inflammatory and immunosuppressive action through Oleum Tiglii being caused mouse ear inflammatory inhibition test and mouse hemolytic antibody generation inhibition test and vitro lymphocyte proliferation inhibition test.Under doses, after 30 days, can cause clear and definite male antifertility effect through administration to male mice and rat respectively in addition.As being used for human anti-inflammatory, immunosuppression, antitumor or male antifertility, 17-hydroxyl triptolide alcohol and analogue Orally-administrable thereof also can be made into injection.
Compound provided by the invention has medicinal efficacy, does not have significant side effects, and is simple and easy to do on the preparation method, is suitable for enforcement.
Be described further below in conjunction with embodiment.
Embodiment 1:
Embodiment 2, get leaf 20kg, with 75～95% extraction using alcohols, after concentrating, in chloroform-water, distribute, the chloroform leachable separates with silica gel column chromatography, with 1～10% ethanol chloroform gradient elution, collects the part that contains 17-hydroxyl triptolide alcohol, again through low pressure silica gel H column chromatography, with hexanaphthene-acetone wash-out, concentrate and concentrate stream part of containing 17-hydroxyl triptolide alcohol, concentrate, separate out crystallization, recrystallization gets pure product (～R in the chloroform
1, R
2=... O ..., R
3=CH
2OH).
Embodiment 3, get the product (～R of above example 1 or example 2
1, R
2=... O ..., R
3=CH
2OH), be dissolved in the dehydrated alcohol, feed dried HCl and place a few hours, the heating concentration of reaction solution, and add equivalent distilled water, and use chloroform extraction again, concentrate chloroform solution, use the silica gel H column chromatography for separation, hexanaphthene-acetone wash-out, crude product chloroform recrystallization gets pure product (～R
1=-Cl, R
2=OH, R
3=CH
2OH),
Embodiment 4, get the product dissolving of above example 1 or example 2 methods after, add anhydrous HF, behind the reaction certain hour, add 5%NaHCO
3The aqueous solution is washed to PH neutrality, and chloroform extraction is told chloroform layer, concentrates post crystallization, gets resultant (～R
1=-F, R
2=OH, R
3=CH
2OH).
Embodiment 5, with after the dissolving of the product of above example 1 or example 2 methods, add entry and dense HBr, refluxed tens of minutes, add 2 times of water gagings after the reaction, partial solvent is removed in decompression, measures dichloromethane extraction 3 times with 1 times, with anhydrous Na
2SO
4The dry methylene chloride layer, concentrating under reduced pressure separates through the silica gel H post, hexanaphthene-acetone wash-out, crude product gets pure product (～R through recrystallizing methanol
1=-Br, R
2=OH, R
3=CH
2OH).
Embodiment 6, with sodium iodide, sodium-acetate, acetic acid and propionic acid mix, and put-30 ℃, the product 22mg that adds example 1 or example 2 methods stirs 0.5h, is poured in the mixed solution of ether water-bearing sodium bisulfate, wash ether layer with a small amount of Sodium hydrogen sulphite solution, wash MgSO again with water
4Drying, concentrating under reduced pressure get product (～R
1=-I, R
2=OH, R
3=CH
2OH).
Embodiment 7, the product of getting example 1 or example 2 methods are dissolved in the 0.3N potassium hydroxide 85% moisture DMSO solution, 100 ℃ of heating 8h, product (～R
1=-OH, R
2=OH, R
3=CH
2OH).
Embodiment 8, in the 2g neutral alumina, add the 200ul anhydrous methanol and stir 0.5h, in the product and the above-mentioned aluminum oxide of impouring with 10ml anhydrous methanol dissolving 10mg example 1 or example 2,60 ℃ of heated and stirred 8h, leach reaction solution, use the methanol-eluted fractions aluminum oxide again, merge and the volatilization methanol solution, concentrated solution separates (eluent is 2% methyl alcohol chloroform) with the silica gel H post, merge required effluent liquid, get product (～R with the chloroform recrystallization
1=-OCH
3, R
2=OH, R
3=CH
2OH).
Embodiment 9, get the product 10mg of example 1 or example 2 methods, dissolving is stirred and is added 5ulBF down
3Ether solution, room temperature is placed 6h, uses 5%NaHCO again
3And water washing, behind anhydrous sodium sulfate drying, concentrating, concentrated solution separates (eluent 2% methyl alcohol chloroform) through silicagel column and gets crude product, gets product (～R with the chloroform recrystallization again
1=-OH, R
2=F, R
3=CH
2OH).
After embodiment 10, the product dissolving, add chromium trioxide-pyridine complex, add the acetic acid solution of chromium trioxide-two arsenic pyridines again, carry out oxidation under the room temperature and promptly get resultant (～R above example 1 or example 2
1, R
2=... O ..., R
3=CHO).
The product of embodiment 11, above example 1 or example 2 is logical O under Pt catalysis
2, promptly get resultant (～R
1, R
2=... O ..., R
3=COOH).
Embodiment 12, get the product of example 11, add the anhydrous methanol dissolving, add boron trifluoride-ether complex, backflow 2h, resultant (～R
1, R
2=... O ..., R
3=COOCH
3).
Embodiment 13, get the product of example 11, add anhydrous alcohol solution, by example 12 methods carry out product (～R
1, R
2=... O ..., R
3=COOCH
2CH
3).
Embodiment 14, get example 10 product 15mg and be dissolved in the dehydrated alcohol, add NaBH
43mg shakes up, and room temperature is placed 3h, gets product (～R
1, R
2=... O ..., R
3=CH
2OH).
Embodiment 15, get example 1 or example 2 products are dissolved in the methylene dichloride, and add HBF
4Diethyl ether solution is put in the ice bath and is stirred, and adding diazomethane diethyl ether solution continues to stir 0.5h, flings to solvent, gets crude product, separates (eluent is 2% methyl alcohol chloroform) through silica gel column chromatography, gets product (～R
1, R
2=... O ..., R
3=CH
2OCH
3).
In embodiment 16, the product adding 1ml pyridine, in the rearmounted ice bath of stirring and dissolving, stir and drip the 0.8ml thionyl chloride down 15mg example 1 or example 2.Remove ice bath, continue to stir 4h, solution ether extraction three times merge ether solution, and anhydrous Na is used in washing
2SO
4Dry back concentrates, and recrystallization gets product (～R
1, R
2=... O ..., R
3=CH
2Cl).
Embodiment 17, get anhydrous propanone 20mg, add anhydrous K F100mg, heating adds example 16 product 20mg again, and reflux 8h placed liquid, leached solution, concentrating under reduced pressure, through silicagel column separate product (～R
1, R
2=... O ..., R
3=CH
2F).
Embodiment 18, the product of example 1 or example 2 is dissolved in the anhydrous propanone, stirs and add potassiumiodide-phosphoric acid liquid down, backflow 2h, silicagel column separates (2% methyl alcohol chloroform is an eluent), product (～R
1, R
2=... O ..., R
3=CH
2I).
Embodiment 19, get example 1 or example 2 product 10mg, add 0.25ml aceticanhydride and 0.25ml pyridine, the 3.5h that refluxes in boiling water bath is put coldly, separates out crystallization, places about 20 minutes in refrigerator, leaches crystallization, with a small amount of absolute ethanol washing 3 times, dry must product (～R
1, R
2=... O ..., R
3=CH
2OCOCH
3).
Embodiment 20, branch are got embodiment 10 products, react by example 3,4,5,6,9 methods respectively, get product (～R separately
1=-Cl, R
2=OH, R
3=CHO;～R
1=-F, R
2=OH, R
3=CHO;～R
1=-Br, R
2=OH, R
3=CHO;～R
1=-I, R
2=OH, R
3=CHO;～R
1=-OH, R
2=F, R
3=CHO).
Embodiment 21, branch are got example 12, example 13 products, react by example 3,4,5,6,9 methods respectively, get product (～R separately
1=Cl, R
2=OH, R
3=COOCH
3;～R
1=-F, R
2=OH, R
3=COOCH
3;～R
1=-Br, R
2=OH, R
3=COOCH
3;～R
1=-I, R
2=OH, R
3=COOCH
3;～R
1=-OH, R
2=F, R
3=COOCH
3;～R
1=-Cl, R
2=OH, R
3=COOCH
2CH
3;～R
1=-F, R
2=OH, R
3=COOCH
2CH
3;～R
1=-Br, R
2=OH, R
3=COOCH
2CH
3;～R1=-I, R
2=OH, R
3=COOCH
2CH
3;～R
1=-OH, R
2=F, R
3=COOCH
2CH
3).
Embodiment 22, the product with example 16,17,18,19 methods is a reactant respectively, undertaken by example 3, example 6 methods respectively, product (～R separately
1=-Cl, R
2=OH, R
3=CH
2Cl;～R
1=-I, R
2=OH, R
3=CH
2Cl;～R
1=-Cl, R
2=OH, R
3=CH
2F;～R
1=-I, R
2=OH, R
3=CH
2F;～R
1=-Cl, R
2=OH, R
3=CH
2I;～R
1=-I, R
2=OH, R
3=CH
2I;～R
1=-Cl, R
2=OH, R
3=CH
2OCOCH
3;～R
1=-I, R
2=OH, R
3=CH
2OCOCH
3).
Embodiment 23, be reactant, undertaken by example 9 methods with example 17 products, after the separation two kinds of product (～R
1=-F, R
2=OH, R
3=CH
2F and～R
1=-OH, R
2=F, R
3=CH
2F).
Claims (3)
1, compound 17-hydroxyl triptolide alcohol and analogue thereof is characterized in that structural formula is
Wherein～R
1=-F ,-Cl ,-Br ,-I ,-OH or-OCH
3,
R
2=F, Cl or OH,
R
3=CH
2F, CH
2Cl, CH
2Br, CH
2I, CH
2OH, CH
2OCH
3, CHO, CH
2OCOCH
3, COOHCOOCH
2CH
3Or CH
3COO,
～R
1, R
2=... 0 ... (α type epoxy group(ing))
(～R
1, R
2=... 0 ..., R
3=CH
2Be 17-hydroxyl triptolide alcohol during OH, all the other are its analogue).
2, the preparation method of 17-hydroxyl triptolide alcohol and analogue thereof, after it is characterized in that getting tripterygium leaf or trypterygine other parts poach and removing slag, extract or ethanol directly extracts with organic solvent or compounded organic solvent, the gained sample liquid is carried out chromatography, carry out wash-out with organic solvent or compounded organic solvent then, the effluent liquid that contains 17-hydroxyl triptolide alcohol concentrates the back recrystallization and gets 17-hydroxyl triptolide alcohol, this compound is directly used as product or is carried out building-up reactions with the R-H compound, or 17 functional group is oxidized to aldehyde or acid, or and BF
3-etherate reaction, or 17 hydroxy halogenos become X, or 17 hydroxyls and diazomethane generation ether, or with H-R ' generation ester, or 17 be oxidized to acid back and H-R ' generation ester, or above-mentioned 17 halides or ether or ester or aldehyde and HR carry out building-up reactions, separate then, purifying, its R=F, Cl, Br, I, OH, OCH
3, X=F, Cl, Br, I, R '=CH
3COO, CH
3O, CH
3CH
2O.
3, by the 17-hydroxyl triptolide alcohol of claim 2 regulation and the preparation method of analogue thereof, it is characterized in that preparation technology is one of following flow process,
B, get leaf 20kg, with 75～95% extraction using alcohols, after concentrating, in chloroform-water, distribute, the chloroform leachable separates with silica gel column chromatography, with 1～10% ethanol chloroform gradient elution, collects the part that contains 17-hydroxyl triptolide alcohol, again through low pressure silica gel H column chromatography, with hexanaphthene-acetone wash-out, concentrate and concentrate stream part of containing 17-hydroxyl triptolide alcohol, concentrate, separate out crystallization, recrystallization gets pure product (～R in the chloroform
1, R
2=... O ..., R
3=CH
2OH),
C, get the product (～R of above a or b
1, R
2=... O R
3=CH
2OH), dissolve in the dehydrated alcohol, feed dried HCl, place a few hours, the heating concentration of reaction solution, and add equivalent distilled water, and use chloroform extraction again, concentrate chloroform solution, use the silica gel H column chromatography for separation, hexanaphthene-acetone wash-out, crude product chloroform recrystallization gets pure product (～R
1=-Cl, R
2=OH, R
3=CH
2OH),
D, get the product dissolving of above a or b method after, add anhydrous HF, behind the reaction certain hour, add 5%NaHCO
3The aqueous solution is washed to PH neutrality, and chloroform extraction is told chloroform layer, concentrates post crystallization (～R
1=-F, R
2=OH, R
3=CH
2OH),
E, get the product dissolving of above a or b method after, put in the ice bath and constantly stir, add a certain amount of SOCl
2, speed control is at 3 droplets/minute, and lasting the stirring 4 hours, uses ether extraction 3 times, and remainder chloroform extraction 3 times concentrate, the silica gel H column chromatography, hexanaphthene-acetone wash-out, crude product gets resultant (～R with the chloroform recrystallization
1, R
2=... O ..., R
3=CH
2Cl),
After f, the product dissolving, add chromium trioxide-arsenic pyridine complex compound, add the acetic acid solution of chromium trioxide-two arsenic pyridines again, carry out oxidation under the room temperature and promptly get resultant (～R above a or b
1, R
2=... O ..., R
3=CHO),
The product of g, above a or b is logical O under Pt catalysis
2, promptly get product (～R
1, R
2=... O ..., R
3=COOH).
H, the product of a or b method is dissolved in the methylene dichloride, and adds HBF
4Diethyl ether solution is put in the ice bath and is stirred, and adds the diazomethane diethyl ether solution, continues to stir 0.5h, enriched material through silica gel column chromatography separate product (～R
1, R
2=... O ..., R
3=CH
2OCH
3),
I, get the product 10mg of a or b method, add 0.25ml aceticanhydride and 0.25ml pyridine, the 3.5h that refluxes in boiling water bath is put coldly, separates out crystallization, places about 20 minutes in refrigerator, leaches crystallization, with a small amount of absolute ethanol washing three times, dry must product (～R
1, R
2=... O ..., R
3=CH
2OCOCH
3),
J, get the resultant of g method, add the anhydrous methanol dissolving, add BF
3-etherate, backflow 2h gets resultant (～R
1, R
2=... O ..., R
3=COOCH
3),
K, f method or e method or h method or i method or j method gained resultant are reacted by the c method respectively separately, resultant separately, be followed successively by～R
1=-Cl R
2=OH R
3=CHO ,～R
1=-Cl R
2=OH R
3=CH
2Cl ,～R
1=-Cl R
2=OH R
3=CH
2OCH
3,～R
1=-Cl R
2=OH R
3=CH
2OCOCH
3,～R
1=-Cl R
2=OH R
3=COOCH
3,
L, get the product 10mg of a or b method, dissolving is stirred and is added 5ul BF down
3Ether solution, room temperature is placed 6h, uses 5%NaHCO again
3And washing, the drying back concentrates, and concentrated solution separates (eluent is 2% methyl alcohol chloroform) through silicagel column and gets crude product, uses the chloroform recrystallization again, gets product (～R
1=-OH, R
2=F, R
3=CH
2OH).
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89105432 CN1052859A (en) | 1989-12-22 | 1989-12-22 | The structure of 17-hydroxyl triptolide alcohol and analogue and preparation method |
| US07/629,411 US5430054A (en) | 1989-12-22 | 1990-12-18 | Preparation methods of diterpene lactone compounds and application of the same to antifertility |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89105432 CN1052859A (en) | 1989-12-22 | 1989-12-22 | The structure of 17-hydroxyl triptolide alcohol and analogue and preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1052859A true CN1052859A (en) | 1991-07-10 |
Family
ID=4856193
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 89105432 Pending CN1052859A (en) | 1989-12-22 | 1989-12-22 | The structure of 17-hydroxyl triptolide alcohol and analogue and preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1052859A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5663335A (en) * | 1996-03-01 | 1997-09-02 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| WO2000063212A1 (en) * | 1999-04-16 | 2000-10-26 | Chengdu Diao Pharmaceutical Group Company Limited | Derivatives of triptolide, and preparation and uses thereof |
| JP2007524581A (en) * | 2003-02-25 | 2007-08-30 | ファーマジェネシス， インコーポレイテッド | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| CN100408583C (en) * | 2003-02-25 | 2008-08-06 | 美国泛华医药公司 | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| US7662976B2 (en) | 2002-05-31 | 2010-02-16 | Pharmagenesis, Inc. | Triptolide derivatives for modulation of apoptosis and immunosuppression |
| US7820834B2 (en) | 2003-12-24 | 2010-10-26 | Pharmagenesis, Inc. | Triptolide 5,6-derivatives as immunomodulators and anticancer agents |
| US7863464B2 (en) | 2004-03-02 | 2011-01-04 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| US8048914B2 (en) | 2004-02-09 | 2011-11-01 | Pharmagenesis, Inc. | Methods for isolation of triptolide compounds from Tripterygium wilfordii |
| US8617906B2 (en) | 2004-10-13 | 2013-12-31 | Pharmagenesis, Inc. | Identification and screening of triptolide target molecules |
-
1989
- 1989-12-22 CN CN 89105432 patent/CN1052859A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5663335A (en) * | 1996-03-01 | 1997-09-02 | Pharmagenesis, Inc. | Immunosuppressive compounds and methods |
| WO2000063212A1 (en) * | 1999-04-16 | 2000-10-26 | Chengdu Diao Pharmaceutical Group Company Limited | Derivatives of triptolide, and preparation and uses thereof |
| US7662976B2 (en) | 2002-05-31 | 2010-02-16 | Pharmagenesis, Inc. | Triptolide derivatives for modulation of apoptosis and immunosuppression |
| US7847109B2 (en) | 2002-05-31 | 2010-12-07 | Pharmagenesis, Inc. | Triptolide derivatives for modulation of apoptosis and immunosuppression |
| JP4647587B2 (en) * | 2003-02-25 | 2011-03-09 | ファーマジェネシス， インコーポレイテッド | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| US7417069B2 (en) | 2003-02-25 | 2008-08-26 | Pharmagenesis, Inc. | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| CN100408583C (en) * | 2003-02-25 | 2008-08-06 | 美国泛华医药公司 | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| JP2007524581A (en) * | 2003-02-25 | 2007-08-30 | ファーマジェネシス， インコーポレイテッド | Halogenated triptolide derivatives as immunomodulators and anticancer agents |
| US7820834B2 (en) | 2003-12-24 | 2010-10-26 | Pharmagenesis, Inc. | Triptolide 5,6-derivatives as immunomodulators and anticancer agents |
| US8048914B2 (en) | 2004-02-09 | 2011-11-01 | Pharmagenesis, Inc. | Methods for isolation of triptolide compounds from Tripterygium wilfordii |
| US7863464B2 (en) | 2004-03-02 | 2011-01-04 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| US8426616B2 (en) | 2004-03-02 | 2013-04-23 | Pharmagenesis, Inc. | Triptolide lactone ring derivatives as immunomodulators and anticancer agents |
| US8617906B2 (en) | 2004-10-13 | 2013-12-31 | Pharmagenesis, Inc. | Identification and screening of triptolide target molecules |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69923768T2 (en) | CEPHALOTOXANDERIVATIVE AND METHOD FOR THE PRODUCTION THEREOF | |
| Dickey | Liriodendrin, a new lignan diglucoside from the inner bark of yellow poplar (Liriodendron tulipifera L.) | |
| CN1052859A (en) | The structure of 17-hydroxyl triptolide alcohol and analogue and preparation method | |
| EP0089377B1 (en) | Novel steroid saponins, process for their extraction, and process for preparing 16-dehydropregnenolone therefrom | |
| JPS6056715B2 (en) | Reactive iridoid derivatives and their production method | |
| DE1793679A1 (en) | New intermediates for the production of optically active 13-alkyl-gonapentaenes | |
| Horton et al. | Enolization of aldosulose derivatives. 4-O-acetyl-1, 6-anhydro-2-3-O-isopropylidene-β-D-threo-hex-3-enopyranose, the 3, 4-enediol acetate of a fused-ring keto sugar, and formation of a branched-chain sugar derivative | |
| AT390252B (en) | METHOD FOR PRODUCING 6-DEOXYANTHRACYCLINONES | |
| Ballou | The D-erythro-2, 3-Dihydroxybutyric Acid Monophosphates | |
| JPH085866B2 (en) | Novel aconitine compounds and analgesic / anti-inflammatory agents | |
| DE2343843A1 (en) | MEDICATIONS CONTAINING VICIANOSYLQUERCETINE AS THE ACTIVE SUBSTANCE, AND METHOD FOR THE MANUFACTURE OF THE ACTIVE SUBSTANCES | |
| Fried et al. | Streptomycin. XI. 1 Synthesis of 3, 6-Dimethyl-N-methyl-D-glucosamine2 | |
| Ness et al. | Synthesis of 1, 4, 5-tri-O-benzoyl-2, 3-dideoxy-D-erythro-hex-2-enulopyranose, derivative of a ketose-related glycal having an endocyclic double bond | |
| HAYASHI et al. | Studies on the constituents of Asclepiadaceae Plants. XXXIV. Chemistry of sarcostin | |
| Kirk et al. | An improved route to 19-hydroxypregn-4-ene-3, 20-dione and synthesis of its [19-2 H 2] analogue | |
| CN103641884A (en) | Method for extracting tripchlorolide from tripterygium wilfordii front segment | |
| US6489492B2 (en) | Chiral derivatives of Garcinia acid bearing lactone ring moiety and process for preparing the same | |
| DE2436332A1 (en) | SUBSTITUTED TETRAHYDROFURANS AND PROCESS FOR THEIR PRODUCTION | |
| Smith III et al. | Structures of breynins A and B, architecturally complex orally active, hypocholesterolemic spiroketal glycosides | |
| JPH0372493A (en) | Production of 2'-o-substituted-adenosine-3',5'-cyclic phosphoric acid or its salt | |
| DE1668598A1 (en) | Process for the preparation of new optically active compounds with a bicyclic structure | |
| Nakajima et al. | Synthetic Studies on Carbohydrate Antibiotics: Part I. Synthesis of 6-Deoxy-d-xylo-Hexofuranos-5-ulose Part II. Synthesis of 6-Deoxy-d-arabino-Hexofuranos-5-ulose, the Sugar Component of Hygromycin A | |
| US20030088110A1 (en) | Novel chiral derivatives of hibiscus acid bearing lactone ring moiety, process for preparing the same and a convenient method for the large-scale isolation of hibiscus acid | |
| Hajos et al. | Synthesis and Stereochemistry of Hydrophenanthrenes. III. 1 The Reaction of 1, 3-Dicyclohexyl-1-(1, 2, 3, 9, 10, 10aβ-hexahydro-7-methoxy-2α-phenanthrylc arbonyl) urea with Sodium Alkoxides | |
| SU475852A1 (en) | The method of obtaining steroid sapogeninaphenogenin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |