CN1185244C - Rebescensine A derivatives and preparing process thereof - Google Patents
Rebescensine A derivatives and preparing process thereof Download PDFInfo
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- CN1185244C CN1185244C CNB991011791A CN99101179A CN1185244C CN 1185244 C CN1185244 C CN 1185244C CN B991011791 A CNB991011791 A CN B991011791A CN 99101179 A CN99101179 A CN 99101179A CN 1185244 C CN1185244 C CN 1185244C
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- rubescensine
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- 238000000034 method Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- SDHTXBWLVGWJFT-XKCURVIJSA-N oridonin Chemical class C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12[C@@H](O)CCC(C)(C)[C@H]1[C@H](O)[C@@]3(O)OC2 SDHTXBWLVGWJFT-XKCURVIJSA-N 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- -1 phenyl aldehyde Chemical class 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 5
- 238000006266 etherification reaction Methods 0.000 claims description 4
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000000969 xylosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 2
- 239000003444 phase transfer catalyst Substances 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract description 12
- SLRKFRUSEKUSAF-UHFFFAOYSA-N 2-methylidenecyclopentan-1-one Chemical compound C=C1CCCC1=O SLRKFRUSEKUSAF-UHFFFAOYSA-N 0.000 abstract 1
- CAQAFLRZJHXSIS-UHFFFAOYSA-N oridonin Natural products CC1(C)C=CC(O)C23COC(O)(C(O)C12)C45C(O)C(CCC34)C(=C)C5=O CAQAFLRZJHXSIS-UHFFFAOYSA-N 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 9
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 2
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229930182478 glucoside Natural products 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 2
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ONVABDHFQKWOSV-UHFFFAOYSA-N 16-Phyllocladene Natural products C1CC(C2)C(=C)CC32CCC2C(C)(C)CCCC2(C)C31 ONVABDHFQKWOSV-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001183967 Isodon Species 0.000 description 1
- 241001646826 Isodon rubescens Species 0.000 description 1
- 150000001262 acyl bromides Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000001175 calcium sulphate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229930004069 diterpene Natural products 0.000 description 1
- 125000000567 diterpene group Chemical group 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- ONVABDHFQKWOSV-HPUSYDDDSA-N ent-kaur-16-ene Chemical compound C1C[C@H](C2)C(=C)C[C@@]32CC[C@@H]2C(C)(C)CCC[C@@]2(C)[C@@H]31 ONVABDHFQKWOSV-HPUSYDDDSA-N 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides an oridonin derivative disclosed in the general formula in the specification by changing the tension force and the dissolvability of external methylene cyclopentanone of an alpha-ring on the premise of no destroy to an active center oridonin. The oridonin derivative has high antitumor cytoactive. Simultaneously, the present invention also provides a preparation method of the compound.
Description
The present invention relates to new Oridonin derivative and preparation method thereof.
From the Rabdosia plant, in isolated more than 100 the diterpenes compositions, have more than 30 of certain anti-tumor activity arranged.What wherein have rubescensine A (kaurene type) type has about 17 kinds, and their content in plant with rubescensine A for the highest, its activity research serves as maximum with rubescensine A also.Rubescensine A is the diterpene-kind compound with alpha-methylene cyclopentanone, and its antitumour activity is definite, and by the Chinese scholars broad research, for example Henan Medical Univ. opens pool wood research group and (sees: a, Wang Jinying, Lin Chen, Zhang Tanmu, Acta Pharmacologica Sinica, 1985,6,195.; B, Wu Kongming, Zhang Tanmu, Wang Qingduan, treatment and prevention of tumour research, 1994,21 (4), 208.), and Japanese scholar Fujita research group (sees: Eiich Fujita, Yoshimitsu Nagao, Kimiyoshi Kaneko, Shozo Nakazawa, and Hiroyuki Kuroda, Chem.Pharm.Bull., 29,3208 (1981)), it has all been done a large amount of pharmacological evaluation work, proved that rubescensine A has definite external and intravital anti-tumor activity, its antitumor spectra is also wider, as the human body nasopharyngeal carcinoma cell, human hepatoma cell, human body cervical cancer cell, esophageal cancer cell etc. all have tangible lethal effect.But its activity is all not high, and its IC50 is greater than 1 μ g/ml.In carrying out body, find have the unitary compound of the outer methylene radical cyclopentanone of α-ring on all structures and all have anti-tumor activity, and this unitary compound does not all have activity in the activity research process of anti-mouse ehrlich carcinoma.People such as Japan scholar Fujita think that the active centre of this class diterpene-kind compound is the outer methylene radical cyclopentanone of α-ring; and Japanese scholar has carried out acidylate to 14 hydroxyls; acyl group in the middle of the compound after the acidylate during with C16 is active in the highest, and activity in vivo exceeds 30%～40% than rubescensine A.We find that the anti-tumor activity of all these compounds is all not high enough when summing up the previous work basis, and because poorly water-soluble, thereby limited its use.People such as nearest Liu Chen river (see: Liu Chenjiang, Zhao Zhihong, Chinese Pharmaceutical Journal, 33,577 (1998)) again Rabdosia rubescens and the nearly 30 years research of rubescensine A are summarized, affirmed the definite anticancer therapeutic of rubescensine A equally, and proposed the problem that exists.In a word, desire is developed as new drug with rubescensine A, also need improve its anti-tumor activity, and reduces toxicity as much as possible and improve its solvability.
The objective of the invention is under the prerequisite of not destroying the rubescensine A active centre, by changing the tension force and the solubleness of the outer methylene radical cyclopentanone of α-ring, provide to have the more Oridonin derivative of high anti-tumor activity, the preparation method of this compound is provided simultaneously.
The present invention is achieved by the following technical solutions.
Oridonin derivative, its feature is represented with following general formula:
General formula 1 general formula 2
In general formula 1: R
1Be alkyl or the acyl group of H or C1～C12, or be glucosyl group or galactosyl or xylosyl, R
2Be H or glucosyl group or galactosyl or xylosyl, or mannose group;
In general formula 2: R
1Alkyl or acyl group for H or C1～C12; R
2, R
3Be respectively the alkyl of C2～C18, or be isopropylidene, benzene methene base.
The method for preparing compound shown in the above-mentioned general formula 1 is:
A, with rubescensine A in the presence of anhydrous slufuric acid ketone with acetone reaction, carry out selectively acylating with selectively acylating reagent again and can obtain the not protected compound of the Cl-OH shown in the formula 3; Or with rubescensine A in the presence of the anhydrous slufuric acid ketone with acetone reaction after, use Ac again
2O-pyridine acidylate obtains the not protected compound of the C6-OH shown in the formula 4;
Formula 3 formulas 4
B, the compound shown in formula 3 or the formula 4 is reacted with tetrem acidylate or triacetyl bromo sugar in the presence of phase-transfer catalyst, and then with gentle deprotection method the protecting group of sugar is removed and promptly to obtain the compound shown in the general formula 1.
The method for preparing compound shown in the above-mentioned general formula 2 is, with rubescensine A selective etherification reagent Bu
2SnO/RX at first carries out selective etherification or reacts with acetone or phenyl aldehyde in the presence of acid,, can obtain the compound shown in the general formula 2 with acylating reagent and its reaction again.
Compound provided by the present invention is on the basis of not destroying original basic framework; by being carried out acidylate, etherificate or glucosides modification, 1,6,7 of rubescensine A and 14 hydroxyls transform; particularly by changing the tension force and the guidance quality of the outer methylene radical cyclopentanone of α-ring, thereby discovery has higher anti-tumor activity with the Oridonin derivative shown in general formula 1 or the general formula 2.Therefore, compared with prior art, Oridonin derivative has very high antitumor cell activity, and its activity generally exceeds 8-10 times of rubescensine A.The contriver adopts the active determination in vitro method that the antitumour activity of compound provided by the invention is tested, make positive control with rubescensine A, find that this compound exceeds 6-10 doubly to the direct killing effect of cancer cells such as human body nasopharyngeal carcinoma, human body cervical cancer, the esophageal carcinoma than rubescensine A.
Embodiment 1 works as R
1=R
2During=H, the preparation of the Oridonin derivative shown in the general formula 1:
In 250 milliliters of single port flasks of reflux condensing tube are housed, add rubescensine A 5 grams (0.0137mol), be dissolved in 120 milliliters of acetone, add 2 gram anhydrous cupric sulfates, under the argon shield; be heated to 50 ℃, reacted 1.5 hours, be chilled to room temperature; elimination copper sulfate adds dilute alkaline soln, uses CHCl
3Extract 3 times, the water backwash is 2 times again, the organic layer anhydrous Na
2SO
4, drying behind the pressure reducing and steaming solvent, is used recrystallizing methanol, obtains needle-like crystal 4.9 grams, productive rate 88.3%.mp:219-221 ℃.
Ultimate analysis (%): calculated value: C:65.38, H:8.11; Measured value: C:65.69, H:8.14.
Spectroscopic analysis: IRv (cm-1): 3314,1710,1648,1451,1381,1080,1067,882;
1H-NMR (CDCl
3) δ ppm:6.14,5.55 (each 1H, s, H17), 5.90 (1H, d, J=11Hz, C6-OH), 4.79 (1H, s, H14), 4.24,4.04 (each 1H, d, J=10Hz, H20), 3.87 (11H, dd, J=10.4,8Hz, H6), 3.46 (1H, m, H1), 3.06 (1H, d, J=9.2Hz, H13), 2.52 (1H, dt, J=8.8,13.6Hz, H12), 1.48-1.62 (2H, m, H2), 1.65,1.32 (each 3H, s, two methyl hydrogen of the acetone that contracts), 1.15 (6H, s, two methyl hydrogen of C4).
Embodiment 2 works as R
1=H, R
2, R
3During=isopropylidene, the preparation method of the Oridonin derivative shown in the general formula 2 is with embodiment 1.
Embodiment 3 works as R
1=ethanoyl, R
2During=H, the preparation of the Oridonin derivative shown in the general formula 1:
In the single port flask of 50ml, add the prepared compound 300mg (0.74mmol) of embodiment 1, be dissolved in 3ml acetic anhydride and the 6ml pyridine stirring reaction 10 hours; Add saturated NaHCO
3Solution stirring is till no bubble is emitted; With ethyl acetate extraction 3 times,, use anhydrous Na SO again with organic layer water repetitive scrubbing
4Dry; Evaporated under reduced pressure is used methanol-water (1: 1) recrystallization at last to pulpous state, gets prism-shaped crystal 2 60mg, productive rate 78.5%, mp:193-195 ℃.
Ultimate analysis: calculated value: C:65.92, H:7.74; Measured value: C:66.18, H:7.46.
Spectroscopic data: IRv (cm-1): 3393,1743,1708,1641,1083,1069,965,913.
1H-NMR (CDCl
3) δ ppm:6.16,5.56 (each 1H, s, H17), 5.80 (1H; d, J=9.2Hz, C6-OH), 4.76 (1H, d; J=1.2Hz, H14), 4.61 (1H, dd, J=5.6; 11.2Hz, H1), 4.22,4.16 (each 1H, d; J=10Hz, OCH2), 3.92 (1H, t; J=9.0Hz, H6), 3.05 (1H, d; J=9.2Hz, H13), 2.47 (1H, m; H12), 1.98 (3H, s, the methyl hydrogen of ethanoyl); 1.65,1.34 (each 3H, s, two methyl hydrogen of the acetone that contracts); 1.18,1.17 (each 3H, s, two methyl hydrogen of C4).
Embodiment 4 works as R
1=ethanoyl, R
2, R
3During=isopropylidene, the preparation method of Oridonin derivative is with embodiment 3 shown in the general formula 2.
Embodiment 5 works as R
1=H, R
2During=glucosyl group, the preparation of the Oridonin derivative shown in the general formula 1:
In the 100ml there-necked flask of reflux condensing tube, constant pressure funnel is housed, add prepared compound 100mg (0.25mmol) among the embodiment 3, be dissolved in the 20ml anhydrous chloroform, add an amount of anhydrous calciumsulphate again; Induction stirring 0.5 hour is every 1 little time-division, three addings 2.5g active A g
2CO
3-diatomite (1: 1) drips the chloroformic solution 30ml of tetrem acylbromide for glucose, reacts end in 3 hours; Filter, evaporate to dryness, silica gel column chromatography separate 1-acetyl-6-O-glucosides compound 220mg.Then, in the single port flask of 50ml, add this glucosides compound 500mg (0.51mol), be dissolved in the 25ml methyl alcohol, add 7ml ammoniacal liquor, room temperature induction stirring reaction 24 hours; Evaporated in vacuo gets faint yellow soup compound, and chromatographic separation gets 6-O-glucosides compound 220mg, productive rate 70%, mp:181-183 ℃ with acetone recrystallization.
Ultimate analysis (%): calculated value: C:59.58, H:7.59; Measured value: C:59.89, H:7.57.
Spectroscopic data: IRv (cm-1): 3468,2945,1737,1703,1651,1370,1056,1039,910.
1H-NMR (CD3COCD3) δ ppm:5.95,5.46 (each 1H, s, H17), 5.02 (1H, d, J=8Hz, H1), 4.91 (1H, s, H14), 4.32 (2H, m, H20, H6), 4.00 (1H, d, J=10Hz, H20), 3.91 (1H, dd, J=11.2,2.4Hz, H6), 3.71 (1H, dd, J=11.2,5.2Hz, H6), 3.50 (1H, dd, J=11.5,5.2Hz, H1), 3.41-3.20 (4H, m, H3, H4, H5, H2), 2.96 (1H, d, J=8.8Hz, H13), 2.54 (1H, m, H12), 1.62,1.26 (each 3H, s, two methyl hydrogen of acetone contract), 1.20,1.16 (each 3H, s, two methyl hydrogen of C4).
Claims (3)
1, Oridonin derivative, its feature is represented with following general formula:
Or
General formula 1 general formula 2
In general formula 1: R
1Be alkyl or the acyl group of H or C1～C12, or be glucosyl group or galactosyl or xylosyl, R
2Be H or glucosyl group or galactosyl or xylosyl, or mannose group;
In general formula 2: R
1Alkyl or acyl group for H or C1～C12; R
2, R
3Be respectively the alkyl of C2～C18, or be isopropylidene, benzene methene base.
2, a kind of preparation method of compound shown in the general formula 1 according to claim 1 is characterized in that:
A, with rubescensine A in the presence of anhydrous slufuric acid ketone with acetone reaction, carry out selectively acylating with selectively acylating reagent again and can obtain the not protected compound of the C1-OH shown in the formula 3; Or with rubescensine A in the presence of the anhydrous slufuric acid ketone with acetone reaction after, use Ac again
2O-pyridine acidylate obtains the not protected compound of the C6-OH shown in the formula 4;
Formula 3 formulas 4
B, the compound shown in formula 3 or the formula 4 is reacted with tetrem acidylate or triacetyl bromo sugar in the presence of phase-transfer catalyst, and then with gentle deprotection method the protecting group of sugar is removed and promptly to obtain the compound shown in the general formula 1.
3, a kind of preparation method of compound shown in the general formula 2 according to claim 1 is characterized in that: with rubescensine A with selective etherification reagent Bu
2SnO/RX at first carries out selective etherification or reacts with acetone or phenyl aldehyde in the presence of acid, can obtain the compound shown in the general formula 2 with acylating reagent and its reaction again.
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| CNB991011791A CN1185244C (en) | 1999-01-18 | 1999-01-18 | Rebescensine A derivatives and preparing process thereof |
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|---|---|---|---|
| CNB991011791A CN1185244C (en) | 1999-01-18 | 1999-01-18 | Rebescensine A derivatives and preparing process thereof |
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| CN1185244C true CN1185244C (en) | 2005-01-19 |
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ID=5270332
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008022505A1 (en) * | 2006-08-18 | 2008-02-28 | Rui Jin Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine | Use of rubescensine a and derivatives thereof in pharmacy |
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| CN1329083C (en) * | 2004-03-11 | 2007-08-01 | 上海第二医科大学附属瑞金医院 | Method for degrading AML 1-ETO fusion protein and used reagent |
| CN101003528B (en) * | 2006-01-18 | 2010-05-26 | 郑州大学 | Diterpene compound and derivative in kaurene class of new dissymmetry, and its preparation method and uses |
| CN102850369B (en) * | 2011-06-29 | 2014-12-17 | 中国药科大学 | Nitrogen monoxide donor-type oridonin 1,4-hydroxyl-modified derivative, and its preparation method and application |
| CN102847166B (en) * | 2012-10-11 | 2014-04-09 | 山东大学 | Prodrug of oridonin with polyethylene glycol serving as vector and preparation method thereof |
| EP2981529B1 (en) | 2013-04-05 | 2021-07-14 | The Board of Regents of The University of Texas System | Oridonin analogs, compositions, and methods related thereto |
| CN103896958B (en) * | 2014-04-22 | 2016-08-24 | 中国药科大学 | Oridonin and ent-6,7-open loop dammara ene-type derivative purposes in terms of preparing antituberculotic thereof |
| CN104327089A (en) * | 2014-10-16 | 2015-02-04 | 深圳市健元医药科技有限公司 | Water-soluble oridonin derivative and preparation method thereof |
| CN108864132B (en) * | 2018-08-09 | 2020-06-02 | 上海寰竞商务咨询有限公司 | Oridonin derivatives, and preparation method and application thereof |
-
1999
- 1999-01-18 CN CNB991011791A patent/CN1185244C/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008022505A1 (en) * | 2006-08-18 | 2008-02-28 | Rui Jin Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine | Use of rubescensine a and derivatives thereof in pharmacy |
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