CN101838251A - Method for semi-synthesizing paclitaxel and docetaxel - Google Patents
Method for semi-synthesizing paclitaxel and docetaxel Download PDFInfo
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Abstract
The invention discloses a method for semi-synthesizing paclitaxel and docetaxel. The method for semi-synthesizing the paclitaxel sequentially comprises the following steps of: selectively stripping off C-13 acetyl of 13-acetyl-9-dihydro baccatin III to obtain a compound IM1; protecting C-7 hydroxy of the compound IM1 with a protective group to obtain a compound IM2; carrying out condensation reaction on the compound IM2 and a compound S1 and a compound S2 respectively to obtain a compound IM3 and a compound IM5; oxidizing C-9 hydroxy of the compound IM3 and the compound IM5 with oxidant to obtain a compound IM4 and a compound IM6 respectively; stripping off the C-7 protective group and the R3 protective group of the compound IM4 to obtain the paclitaxel; and stripping off the C-7 protective group, R3 protective group and acetyl of the compound IM6 to obtain the docetaxel. The method has the advantages of high yield of final products, low cost, and easy implementation.
Description
Technical field
The invention belongs to the synthetic field of medicine, be specifically related to a kind of method by 13-ethanoyl-semi-synthetic taxol of 9-dihydro baccatin III and Docetaxel.
Background technology
Cancer, medical terminology also claim malignant tumour, and the control growth and proliferation of cell mechanism of serving as reasons is not normal and the big class disease that causes has become one of disease of serious harm human health.In China, cancer has become the second largest deadly cause of disease that is only second to cardiovascular and cerebrovascular diseases.
Taxol (Paclitaxel) is the diterpene-kind compound that separation and Extraction obtains from the bark of taxaceae Chinese yew genus plants, is a kind of novel microtubule stabilizer, has unique antitumour activity.Taxol is by combining with the cell tubulin, promote tubulin polymerization and accumulate a large amount of microtubules in cell, the various functions of cell have been disturbed in the accumulation of these microtubules, particularly make cell fission stop at m period, block the proper splitting of cell, reached anticancer effect.Docetaxel (Docetaxel) is taxol to be carried out in structural modification and the transformation process by the synthetic gained of semisynthesis.The antitumous effect mechanism of Docetaxel is identical with taxol, but with respect to taxol, it is good that it has bioavailability, and toxic side effect is little, the antitumour activity advantages of higher.Simultaneously because its water-soluble increase, make the easier preparation of making of Docetaxel.
Since drugs approved by FDA taxol and Docetaxel were used for the treatment of advanced ovarian cancer, the range of application of taxol and Docetaxel was expanded gradually, has become widely used clinically first-selected cancer therapy drug.But owing to taxol is detected in the Chinese yew genus plants bark, this seeds quantity rareness, poor growth, 1 kilogram of taxol of actual production needs about 30 tons of bark of Ramulus et folium taxi cuspidatae, and simple extraction separation can not satisfy market demand far away.1988, people such as Denis at first utilized 10-deacetylate Bakating III to obtain taxol by semisynthetic method.1993, Holton used beta-lactam and 10-deacetylate Bakating III link coupled method first, the efficient semi-synthetic taxol that obtains.The taxol of selling on the market is mainly derived from natural Japanese yew alcohol that separation and Extraction obtains from Chinese yew genus plants bark, branch and leaf and the semi-synthetic taxol that is made by chemistry route by intermediate 10-deacetylate Bakating III; 10-deacetylate Bakating III content in Ramulus et folium taxi cuspidatae is also less; and 13-ethanoyl-9-dihydro baccatin III exists in the Chinese yew powder in a large number; if can be the semi-synthetic taxol of raw material with it; for protection Chinese yew species and resource; increase the taxol market supply; reduce the oncotherapy expense, be significant.
At present disclosed is the method for raw material taxol biosynthesis with 13-ethanoyl-9-dihydro baccatin III, problems such as ubiquity the finished product yield is low, production cost height.
Summary of the invention
Technical problem to be solved by this invention provides a kind of the finished product yield height, the method by 13-ethanoyl-semi-synthetic taxol of 9-dihydro baccatin III that cost is low.
Another technical problem to be solved by this invention provides a kind of the finished product yield height, the method by 13-ethanoyl-semi-synthetic Docetaxel of 9-dihydro baccatin III that cost is low.
For solving the problems of the technologies described above, the invention provides a kind of semisynthesis of taxol, in turn include the following steps:
(1) be raw material with 13-ethanoyl-9-dihydro baccatin III, selectivity is sloughed the C-13 ethanoyl, obtains Compound I M1;
(2) with the C-7 hydroxyl of hydroxyl protecting group protection Compound I M1, obtain Compound I M2;
(3) Compound I M2 and compound S 1 are carried out condensation reaction, obtain Compound I M3;
(4) with the C-9 hydroxyl oxidize of oxygenant, obtain Compound I M4 with Compound I M3;
(5) slough C-7 blocking group and the R3 protecting group of Compound I M4, obtain taxol;
The structural formula of described Compound I M1 is as follows:
Described Compound I M2, IM3, IM4, S1 have following general formula:
Wherein R2 is a hydroxyl protecting group, and R3 is a protecting group.
In the semisynthesis of above-mentioned taxol, carry out the C-13 ethanoyl that selectivity is sloughed 13-ethanoyl-9-dihydro baccatin III with R1Li solution in the described step 1, wherein R1 is selected from methyl, normal-butyl, sec-butyl or the tertiary butyl.
In the semisynthesis of above-mentioned taxol, with the C-7 hydroxyl of R2C1 protection Compound I M1, wherein R2 is selected from methyldiphenyl base silica-based (MDPS), 3,5-dimethylphenyl silica-based (DMPS), trimethyl silicon based (TMS) or triethyl silica-based (TES) in the described step 2.
In the semisynthesis of above-mentioned taxol, described protecting group R3 is selected from mehtoxybenzyl, O-methoxy phenmethyl, meta-methoxy phenmethyl, sec.-propyl or 3,5-dimethoxy phenmethyl.
In the semisynthesis of above-mentioned taxol, the oxygenant in the described step 4 is selected from Dess-Martin (Dai Si-Martin) oxygenant, 2-iodoxy phenylformic acid (IBX), the high ruthenic acid ammonium/N-methylmorpholine of tetrapropyl-N-oxide compound (TPAP/NMO) or hydrogen peroxide.
In the semisynthesis of above-mentioned taxol, the C-7 blocking group and the R3 protecting group of sloughing Compound I M4 with acid in the described step 5, wherein acid is selected from tosic acid, formic acid, acetic acid, trifluoroacetic acid or concentrated hydrochloric acid.
For solving the problems of the technologies described above, the present invention also provides a kind of semisynthesis of Docetaxel, in turn includes the following steps:
(1) selectivity is sloughed the C-13 ethanoyl of 13-ethanoyl-9-dihydro baccatin III, obtains Compound I M1;
(2) with the C-7 hydroxyl of hydroxyl protecting group protection Compound I M1, obtain Compound I M2;
(3) Compound I M2 and compound S 2 are carried out condensation reaction, obtain Compound I M5;
(4) with the C-9 hydroxyl oxidize of oxygenant, obtain Compound I M6 with Compound I M5;
(5) slough C-7 blocking group and the R3 protecting group of Compound I M6, obtain Compound I M7;
(6) selectivity is sloughed the C-10 ethanoyl on the IM7, obtains Docetaxel;
The structural formula of described IM1, IM7 is as follows:
Described IM2, IM5, IM6, S2 have following general formula:
Wherein R2 is a hydroxyl protecting group, and R3 is a protecting group.
In the semisynthesis of above-mentioned Docetaxel, carry out the C-13 ethanoyl that selectivity is sloughed 13-ethanoyl-9-dihydro baccatin III with R1Li solution in the described step 1, wherein R1 is selected from methyl, normal-butyl, sec-butyl or the tertiary butyl.
In the semisynthesis of above-mentioned Docetaxel; with the C-7 hydroxyl of R2C1 protection Compound I M1, wherein R2 is selected from methyldiphenyl base silica-based (MDPS), 3,5-dimethylphenyl silica-based (DMPS), trimethyl silicon based (TMS) or triethyl silica-based (TES) in the described step 2.
In the semisynthesis of above-mentioned Docetaxel, described R3 is selected from mehtoxybenzyl, O-methoxy phenmethyl, meta-methoxy phenmethyl, sec.-propyl or 3,5-dimethoxy phenmethyl.
In the semisynthesis of above-mentioned Docetaxel, the oxygenant in the described step 4 is selected from Dess-Martin (Dai Si-Martin) oxygenant, 2-iodoxy phenylformic acid (IBX), the high ruthenic acid ammonium/N-methylmorpholine of tetrapropyl-N-oxide compound (TPAP/NMO) or hydrogen peroxide.
In the semisynthesis of above-mentioned Docetaxel, the C-7 blocking group and the R3 protecting group of sloughing Compound I M6 with acid in the described step 5, wherein acid is selected from tosic acid, formic acid, acetic acid, trifluoroacetic acid or concentrated hydrochloric acid.
In the semisynthesis of above-mentioned Docetaxel, slough C-10 ethanoyl on the Compound I M7 with sodium bicarbonate and hydrogen peroxide selectivity in the described step 6.
The present invention contrasts prior art following beneficial effect: it is raw material that the present invention adopts 13-ethanoyl-9-dihydro baccatin III, sloughs the C-13 ethanoyl earlier, again with protecting group protection C-7 hydroxyl; Carry out condensation reaction with compound S 1, S2 then, again with oxygenant with the C-9 hydroxyl oxidize, slough the C-7 protecting group at last; R3 protecting group and ethanoyl obtain taxol and Docetaxel, the final product yield height that this processing method obtains; technology is simple, realizes easily.
Description of drawings
Fig. 1 is the semi-synthetic route map of taxol of the present invention;
Fig. 2 is the semi-synthetic route map of Docetaxel of the present invention;
Fig. 3 is the semi-synthetic route map of taxol in the embodiment of the invention one;
Fig. 4 is the semi-synthetic route map of Docetaxel in the embodiment of the invention two.
Embodiment
Below in conjunction with specific embodiment the present invention is further described, but not as a limitation of the invention.
Embodiment one
The preparation of step 1,9-dihydro baccatin III (Compound I M1)
100g13-ethanoyl-9-dihydro baccatin III (9-DHAB) is dissolved in the 2L tetrahydrofuran (THF) (THF); temperature of reaction system is reduced to-70 ℃; the lithium methide of 600 milliliters of 1.6mol/l drips in the reaction system then, keeps temperature of reaction system and keeps 3 hours at-70 ℃.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the ammonium chloride solution stopped reaction.Organic layer saturated common salt water washing, dry back concentrates.Concentrated solution gets 74g9-dihydro baccatin III (Compound I M1) with 200 milliliters of methylene dichloride recrystallizations after the filtration, yield is 80%.
74g Compound I M1 and 35.3gDMAP (4-Dimethylamino pyridine) are dissolved in the 1L methylene dichloride (DCM), and temperature of reaction system is reduced near 0 ℃, and 58.5gMDPSCl drips in the reaction system then, keep temperature of reaction system and keep 2 hours at 0 ℃.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the entry stopped reaction.Organic layer saturated common salt water washing, dry back concentrates.Concentrated solution is with 75 milliliters of methylene dichloride/75 ml n-hexane recrystallizations, after the filtration 74g7-methyldiphenyl base silica-based-9-dihydro baccatin III (Compound I M2), yield is 75%.
Step 3,2 '-to mehtoxybenzyl-7-methyldiphenyl base silica-based-preparation of 9-dihydro taxol (Compound I M3)
30g Compound I M2 and 30g (4S; 5R)-N-benzoyl-2-p-methoxyphenyl-4-phenyl-5-carboxyl-1; 3-oxazolidine (compound S 1) is dissolved in 300 milliliters of dry toluenes; temperature of reaction system is maintained room temperature; in reaction system, add 3 normal DCC and 0.6 normal DMAP, keep temperature of reaction system and kept 2 hours in room temperature.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the entry stopped reaction.Organic layer saturated common salt water washing, dry back concentrates.Obtain behind the concentrated solution column chromatography 43.5g2 '-to mehtoxybenzyl-7-methyldiphenyl base silica-based-9-dihydro taxol (Compound I M3), yield is 96%.
The preparation of step 4,2 '-p-methoxyphenyl methyl-silica-based taxol of 7-methyldiphenyl base (Compound I M4)
43.5g Compound I M3 is dissolved in 400 milliliters of methylene dichloride, and temperature of reaction system is maintained room temperature, adds the 43.5gDess-Martin oxygenant in reaction system, keeps temperature of reaction system and keeps 15 hours in room temperature.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the entry stopped reaction.Organic layer concentrates with saturated sodium bisulfite solution, saturated common salt water washing, dry back.Obtain 31g2 '-p-methoxyphenyl methyl-silica-based taxol of 7-methyldiphenyl base (Compound I M4) behind the concentrated solution column chromatography, yield is 72%.
The preparation of step 5, taxol
30g Compound I M4 is dissolved in 300 ml methanol, and temperature of reaction system is maintained room temperature, adds 2.1g tosic acid (p-TsOH) in reaction system, keeps temperature of reaction system and keeps half hour in room temperature.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the anhydrous sodium bicarbonate stopped reaction.It is dry concentrated to filter the back organic layer.Obtain the 20.7g taxol behind the concentrated solution column chromatography, yield is 95%.20.7g Docetaxel obtains 99.9% above purity product 19g with acetone/normal hexane (100/200ml) recrystallization.
Embodiment two:
The preparation of step 1,9-dihydro baccatin III (Compound I M1)
100g13-ethanoyl-9-dihydro baccatin III (9-DHAB) is dissolved in the 2L tetrahydrofuran (THF), temperature of reaction system is reduced to-70 ℃, and the lithium methide of 600 milliliters of 1.6mol/l drips in the reaction system then, keeps temperature of reaction system and keeps 3 hours at-70 ℃.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the ammonium chloride solution stopped reaction.Organic layer saturated common salt water washing, dry back concentrates.Concentrated solution gets 74g Compound I M1 with 200 milliliters of methylene dichloride recrystallizations after the filtration, yield is 80%.
74g Compound I M1 and 35.3gDMAP are dissolved in the 1L methylene dichloride, and temperature of reaction system is reduced near 0 ℃, and 58.5g MDPSCl drips in the reaction system then, keep temperature of reaction system and keep 2 hours at 0 ℃.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the entry stopped reaction.Organic layer saturated common salt water washing, dry back concentrates.Concentrated solution is with 75 milliliters of methylene dichloride/75 ml n-hexane recrystallizations, after the filtration 74g7-methyldiphenyl base silica-based-9-dihydro baccatin III (Compound I M2), yield is 75%.
Step 3,2 '-to mehtoxybenzyl-7-methyldiphenyl base silica-based-preparation of 10-ethanoyl-9-dihydro Docetaxel (Compound I M5)
30g Compound I M2 and 30g compound (4S, 5R)-N-tertbutyloxycarbonyl-2-p-methoxyphenyl-4-phenyl-5-carboxyl-1,3-oxazolidine (compound S 2) is dissolved in 300 milliliters of dry toluenes, temperature of reaction system is maintained room temperature, in reaction system, add 3 normal DCC and 0.6 normal DMAP, keep temperature of reaction system and kept 2 hours in room temperature.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the entry stopped reaction.Organic layer saturated common salt water washing, dry back concentrates.Obtain behind the concentrated solution column chromatography 43.5g2 '-to mehtoxybenzyl-7-methyldiphenyl base silica-based-10-ethanoyl-9-dihydro Docetaxel (Compound I M5), yield is 96%.
Step 4,2 '-to mehtoxybenzyl-7-methyldiphenyl base silica-based-preparation of 10-ethanoyl-Docetaxel (Compound I M6)
43.5g Compound I M5 is dissolved in 400 milliliters of methylene dichloride, and temperature of reaction system is maintained room temperature, adds the 43.5gDess-Martin oxygenant in reaction system, keeps temperature of reaction system and keeps 15 hours in room temperature.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the entry stopped reaction.Organic layer concentrates with saturated sodium bisulfite solution, saturated common salt water washing, dry back.Obtain behind the concentrated solution column chromatography 31g2 '-to mehtoxybenzyl-7-methyldiphenyl base silica-based-10-ethanoyl-Docetaxel (Compound I M6), yield is 72%.
The preparation of step 5,10-ethanoyl-Docetaxel (Compound I M7)
30g Compound I M6 is dissolved in 300 ml methanol, and temperature of reaction system is maintained room temperature, adds the 2.1g tosic acid in reaction system, keeps temperature of reaction system and keeps half hour in room temperature.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the anhydrous sodium bicarbonate stopped reaction.It is dry concentrated to filter the back organic layer.Obtain 20.7g10-ethanoyl-Docetaxel (Compound I M7) behind the concentrated solution column chromatography, yield is 95%.
The preparation of step 6, Docetaxel
20g Compound I M7 is dissolved in 200 milliliters of tetrahydrofuran (THF)s, and temperature of reaction system is maintained room temperature, adds 30 normal sodium bicarbonates and 60 normal hydrogen peroxide in reaction system, keeps temperature of reaction system and keeps 15 hours in room temperature.The sampling monitoring reaction, intact to the raw material completely consumed, in reaction system, add the entry stopped reaction.Use ethyl acetate extraction, separate the organic layer saturated sodium bisulfite solution, the saturated common salt water washing that obtain, dry back concentrates.Obtain the 10g Docetaxel behind the concentrated solution column chromatography, yield is 53%.The 10g Docetaxel obtains 99.9% above purity product 9.5g with acetone/normal hexane (100/200ml) recrystallization.
Though the present invention discloses as above with preferred embodiment; right its is not in order to qualification the present invention, any those skilled in the art, without departing from the spirit and scope of the present invention; when can doing a little modification and perfect, so protection scope of the present invention is when with being as the criterion that claims were defined.
Claims (13)
1. the semisynthesis of a taxol is characterized in that in turn including the following steps:
(1) be raw material with 13-ethanoyl-9-dihydro baccatin III, selectivity is sloughed the C-13 ethanoyl, obtains Compound I M1;
(2) with the C-7 hydroxyl of hydroxyl protecting group protection Compound I M1, obtain Compound I M2;
(3) Compound I M2 and compound S 1 are carried out condensation reaction, obtain Compound I M3;
(4) with the C-9 hydroxyl oxidize of oxygenant, obtain Compound I M4 with Compound I M3;
(5) slough C-7 blocking group and the R3 protecting group of Compound I M4, obtain taxol;
The structural formula of described Compound I M1 is as follows:
Described Compound I M2, IM3, IM4, S1 have following general formula:
Wherein R2 is a hydroxyl protecting group, and R3 is a protecting group.
2. the semisynthesis of taxol according to claim 1; it is characterized in that; carry out the C-13 ethanoyl that selectivity is sloughed 13-ethanoyl-9-dihydro baccatin III with R1Li solution in the described step 1, wherein R1 is selected from methyl, normal-butyl, sec-butyl or the tertiary butyl.
3. the semisynthesis of taxol according to claim 1 is characterized in that, in the described step 2 with the C-7 hydroxyl of R2C1 protection Compound I M1, wherein R2 be selected from that the methyldiphenyl base is silica-based, 3,5-dimethylphenyl is silica-based, trimethyl silicon based or triethyl is silica-based.
4. the semisynthesis of taxol according to claim 1 is characterized in that, described protecting group R3 is selected from mehtoxybenzyl, O-methoxy phenmethyl, meta-methoxy phenmethyl, sec.-propyl or 3,5-dimethoxy phenmethyl.
5. the semisynthesis of taxol according to claim 1 is characterized in that, the oxygenant in the described step 4 is selected from Dess-Martin oxygenant, 2-iodoxy phenylformic acid, the high ruthenic acid ammonium/N-methylmorpholine of tetrapropyl-N-oxide compound or hydrogen peroxide.
6. the semisynthesis of taxol according to claim 1 is characterized in that, the C-7 blocking group and the R3 protecting group of sloughing Compound I M4 with acid in the described step 5, and wherein acid is selected from tosic acid, formic acid, acetic acid, trifluoroacetic acid or concentrated hydrochloric acid.
7. the semisynthesis of a Docetaxel is characterized in that in turn including the following steps:
(1) selectivity is sloughed the C-13 ethanoyl of 13-ethanoyl-9-dihydro baccatin III, obtains Compound I M1;
(2) with the C-7 hydroxyl of hydroxyl protecting group protection Compound I M1, obtain Compound I M2;
(3) Compound I M2 and compound S 2 are carried out condensation reaction, obtain Compound I M5;
(4) with the C-9 hydroxyl oxidize of oxygenant, obtain Compound I M6 with Compound I M5;
(5) slough C-7 blocking group and the R3 protecting group of Compound I M6, obtain Compound I M7;
(6) selectivity is sloughed the C-10 ethanoyl on the IM7, obtains Docetaxel;
The structural formula of described IM1, IM7 is as follows:
Described IM2, IM5, IM6, S2 have following general formula:
Wherein R2 is a hydroxyl protecting group, and R3 is a protecting group.
8. the semisynthesis of Docetaxel according to claim 7; it is characterized in that; carry out the C-13 ethanoyl that selectivity is sloughed 13-ethanoyl-9-dihydro baccatin III with R1Li solution in the described step 1, wherein R1 is selected from methyl, normal-butyl, sec-butyl or the tertiary butyl.
9. the semisynthesis of Docetaxel according to claim 7; it is characterized in that; in the described step 2 with the C-7 hydroxyl of R2C1 protection Compound I M1, wherein R2 be selected from that the methyldiphenyl base is silica-based, 3,5-dimethylphenyl is silica-based, trimethyl silicon based or triethyl is silica-based.
10. the semisynthesis of taxol according to claim 7 is characterized in that, described R3 is selected from mehtoxybenzyl, O-methoxy phenmethyl, meta-methoxy phenmethyl, sec.-propyl or 3,5-dimethoxy phenmethyl.
11. the semisynthesis of Docetaxel according to claim 7 is characterized in that, the oxygenant in the described step 4 is selected from Dess-Martin oxygenant, 2-iodoxy phenylformic acid, the high ruthenic acid ammonium/N-methylmorpholine of tetrapropyl-N-oxide compound or hydrogen peroxide.
12. the semisynthesis of Docetaxel according to claim 7; it is characterized in that; the C-7 blocking group and the R3 protecting group of sloughing Compound I M6 with acid in the described step 5, wherein acid is selected from tosic acid, formic acid, acetic acid, trifluoroacetic acid or concentrated hydrochloric acid.
13. the semisynthesis of Docetaxel according to claim 7 is characterized in that, sloughs C-10 ethanoyl on the Compound I M7 with sodium bicarbonate and hydrogen peroxide selectivity in the described step 6.
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| WO2011134067A1 (en) * | 2010-04-29 | 2011-11-03 | 6570763 Canada Inc. | Novel amino acid molecule and uses thereof |
| CN114656427A (en) * | 2022-03-31 | 2022-06-24 | 上海健佑生物科技有限公司 | Taxol anticancer drug and synthesis method thereof |
| CN114751876A (en) * | 2022-01-24 | 2022-07-15 | 上海健佑生物科技有限公司 | Method for synthesizing rivastigmine and docetaxel from 9-dihydro-13-acetylbaccatin III |
| CN115057833A (en) * | 2021-12-16 | 2022-09-16 | 上海健佑生物科技有限公司 | Synthetic route and intermediate compound of anticancer drug cabazitaxel |
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| CN1687043A (en) * | 2005-04-04 | 2005-10-26 | 上海三维制药有限公司 | Method for preparing paclitaxel and analog |
| CN101081841A (en) * | 2006-05-29 | 2007-12-05 | 中国科学院上海药物研究所 | Novel 2'-alpha-hydroxyalkyl taxone compound and preparation method thereof |
| CN101088994A (en) * | 2006-06-12 | 2007-12-19 | 上海龙翔生物医药开发有限公司 | Process of synthesizing taxol and docetaxel |
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| CN1687043A (en) * | 2005-04-04 | 2005-10-26 | 上海三维制药有限公司 | Method for preparing paclitaxel and analog |
| CN101081841A (en) * | 2006-05-29 | 2007-12-05 | 中国科学院上海药物研究所 | Novel 2'-alpha-hydroxyalkyl taxone compound and preparation method thereof |
| CN101088994A (en) * | 2006-06-12 | 2007-12-19 | 上海龙翔生物医药开发有限公司 | Process of synthesizing taxol and docetaxel |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011134067A1 (en) * | 2010-04-29 | 2011-11-03 | 6570763 Canada Inc. | Novel amino acid molecule and uses thereof |
| CN115057833A (en) * | 2021-12-16 | 2022-09-16 | 上海健佑生物科技有限公司 | Synthetic route and intermediate compound of anticancer drug cabazitaxel |
| CN114751876A (en) * | 2022-01-24 | 2022-07-15 | 上海健佑生物科技有限公司 | Method for synthesizing rivastigmine and docetaxel from 9-dihydro-13-acetylbaccatin III |
| CN114656427A (en) * | 2022-03-31 | 2022-06-24 | 上海健佑生物科技有限公司 | Taxol anticancer drug and synthesis method thereof |
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