CN111533714A - Baccatin III derivative and preparation method thereof - Google Patents
Baccatin III derivative and preparation method thereof Download PDFInfo
- Publication number
- CN111533714A CN111533714A CN202010440959.2A CN202010440959A CN111533714A CN 111533714 A CN111533714 A CN 111533714A CN 202010440959 A CN202010440959 A CN 202010440959A CN 111533714 A CN111533714 A CN 111533714A
- Authority
- CN
- China
- Prior art keywords
- product
- reaction
- baccatin iii
- preparation
- ratio
- 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.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a baccatin III derivative and a preparation method thereof, belonging to the technical field of preparation of baccatin anticancer drugs, and the key point of the technical scheme is that the baccatin III derivative is 10-deacetyl-2-debenzoyl-2-tigogenoyl baccatin III, and the preparation method comprises the following steps: dissolving 10-DAB in dichloromethane and pyridine, and dropwise adding 2,2, 2-trichloroethyl chloroformate under stirring for reaction to obtain a product I; dissolving the product I with methanol, dropwise adding a methanol solution of benzyl trimethyl ammonium hydroxide while stirring, and reacting to obtain a product II; dissolving the product II in toluene, adding 4-dimethylaminopyridine and tiglic acid, dropwise adding N, N-diisopropylcarbodiimide, and stirring to react to obtain a product III; dissolving the product III in methanol and acetic acid, adding zinc powder, stirring for reaction, purifying the product by column chromatography, and drying to obtain 10-deacetyl-2-debenzoyl-2-tigrolyl baccatin III.
Description
Technical Field
The invention relates to a preparation technology of a baccatin anticancer drug, in particular to a baccatin III derivative and a preparation method thereof.
Background
Taxanes are a series of derivatives which are obtained by separating antitumor active ingredients from plants, modifying the structures of the obtained compounds of the active ingredients and synthesizing. The taxane medicines mainly comprise paclitaxel and docetaxel, and the two compounds have more important positions in the anti-tumor market. Through the development of many years, the research on impurities of paclitaxel and docetaxel is very complete, and the european pharmacopoeia contains a plurality of characteristic impurities of paclitaxel and docetaxel, wherein the paclitaxel impurity a and the docetaxel impurity a contained in the european pharmacopoeia have similar structures (the structures are shown below).
In the prior art, most of paclitaxel and docetaxel are produced by a semi-synthesis process, and the main raw materials of the paclitaxel and the docetaxel are 10-deacetylbaccatin III (10-DAB), a natural product extracted from branches and leaves of taxus chinensis. Both impurities A are finally introduced into paclitaxel/docetaxel from a specific single impurity (10-deacetyl-2-debenzoyl-2-tigloxycarbonyl III, the structure of which is shown in the following formula) in the raw material 10-deacetyl baccatin III, so that the specific single impurity has very important significance for the quality control of the raw material 10-deacetyl baccatin III.
The preparation method of the impurity can not be inquired for obtaining the impurity, but can be inquired for obtaining the preparation method of the taxol impurity A. The literature [ Bruno Gabeta, Nicola fuzzy, Paolo Orsini, et al, Paclitaxel analogs from Taxus x m edia cv. Hicksii [ J ]. Journal of Natural Products,1999,62(2):219- > 223 ] reports the preparation of Paclitaxel impurity A, prepared from 2' -TBS-7-TES-2-debenzoylpaclitaxel as the starting material. It can be seen that the target product is obtained by protecting each hydroxyl group with a silane protecting group, condensing with tiglic acid, and then deprotecting. Referring to this process, 10-deacetyl-2-debenzoyl-2-tigroloyl baccatin III can be prepared from silane-protected 10-DAB. The yield of the silane protection of the hydroxyl group of 10-DAB is relatively low, and the references [ appendix G, Bellor E, Jakupovic S, et al Synthesis of paclitaxel (docetaxel)/2-deacetoxytaxine J dimer [ J ]. Tetrahedron,1999,55(21): 6567) 6576 ] show that a relatively large number (7) of protected products are obtained, and the yield of the target product 7,10,13-Trtes-10-DAB is 14%, and the isolation and purification are complicated due to the excessive products.
Disclosure of Invention
The invention aims to provide a preparation method of a baccatin III derivative, which has the advantages of no obvious by-product in the steps, high yield of a target product, high purity of the target product and capability of large-scale preparation.
The technical purpose of the invention is realized by the following technical scheme:
a preparation method of baccatin III derivatives comprises the following steps: s1, dissolving 10-DAB in dichloromethane and pyridine, dropwise adding 2,2, 2-trichloroethyl chloroformate under stirring to react, adding hydrochloric acid to neutralize to acidity after the reaction is finished, adding dichloromethane to extract, extracting an organic phase with a saturated sodium bicarbonate solution, and concentrating the organic phase to obtain a product I;
s2, dissolving the product I with methanol, dropwise adding a methanol solution of benzyltrimethyl ammonium hydroxide while stirring, immediately adding a saturated ammonium chloride solution after dropwise adding, quenching the reaction, extracting with dichloromethane, collecting an organic phase, and concentrating to obtain a product II;
s3, dissolving the product II in toluene, adding 4-dimethylaminopyridine and tiglic acid, dropwise adding N, N-diisopropylcarbodiimide, stirring for reaction, after the reaction is finished, carrying out suction filtration on a reaction solution, washing a filtrate with dilute hydrochloric acid, a sodium bicarbonate solution and water respectively, and then concentrating an organic phase to obtain a product III;
s4, dissolving the product III in methanol and acetic acid, adding zinc powder, stirring for reaction, after the reaction is finished, carrying out suction filtration on the reaction solution, diluting the filtrate with dichloromethane, then adding a sodium bicarbonate solution into the filtrate for neutralization till no bubbles exist, washing the organic phase with water for 2 times, concentrating, carrying out column chromatography purification on the concentrate, collecting the product section, concentrating and drying to obtain 10-deacetyl-2-debenzoyl-2-tigloxycarpin III;
the reaction route of the preparation process is as follows:
further, in step S1, the ratio of the amount of dichloromethane to the amount of raw material 10-DAB is 5-10V/W, the ratio of the amount of pyridine to the amount of raw material 10-DAB is 5-10V/W, and the ratio of the amount of chloroformic acid-2, 2, 2-trichloroethyl ester to the amount of raw material 10-DAB is 1.2-3.8W/W.
Further, in step S1, 10-DAB is dissolved in dichloromethane and pyridine, and dropwise added with 2,2, 2-trichloroethyl chloroformate under stirring to react at the temperature of 20-30 ℃ for 1-2 h.
Further, in the step S2, the ratio of the methanol to the product I is 10-20V/W; the ratio of the methanol solution of benzyl trimethyl ammonium hydroxide to the product I is 0.5-1.0V/W.
Further, in step S2, the reaction temperature of the quenching reaction is 0-10 ℃.
Further, in the step S3, the ratio of the toluene to the product II is 10-20V/W; the ratio of tiglic acid to the product II is 0.10-0.17W/W, the ratio of 4-dimethylaminopyridine to the product II is 0.01-0.05W/W, and the ratio of N, N-diisopropylcarbodiimide to the product II is 0.4-0.6V/W.
Further, in step S3, the reaction temperature of the stirring reaction is 40 to 60 ℃, and the reaction time of the stirring reaction is 24 to 48 hours.
Further, in the step S4, the ratio of methanol to the product III is 6-20V/W, and the ratio of acetic acid to the product III is 3-5V/W; the ratio of the zinc powder to the product III is 1.5-3W/W.
Further, in step S4, the reaction temperature of the stirring reaction is 15 to 25 ℃, and the reaction time of the stirring reaction is 0.5 to 2 hours.
A baccatin III derivative prepared by a preparation method of the baccatin III derivative is 10-deacetyl-2-debenzoyl-2-tigloxycarpin III, and the structure of the baccatin III derivative is shown as a formula (1):
in conclusion, the invention has the following beneficial effects:
1. the required 10-deacetyl-2-debenzoyl-2-tigloxycalcine III is prepared by four steps, Troc chloroformic acid-2, 2, 2-trichloroethyl is used as a protecting group to protect hydroxyl to replace a silane protecting group used in the prior art, the obtained product I has fewer impurities, the product I can be directly put into subsequent reaction, the whole process only needs to be purified in the last step to obtain a target product, and the yield is high;
2. the reaction condition requirement is low, the preparation reaction is mild, so that the reaction equipment has no strict requirement, and the large-scale industrial production preparation is facilitated.
Drawings
FIG. 1 is a schematic flow diagram of the steps of a process for the preparation of baccatin III derivatives;
FIG. 2 is the MS spectrum (positive ion mode) of 10-deacetyl-2-debenzoyl-2-tigloxycanthin III of example 1;
FIG. 3 is the MS spectrum (negative ion mode) of 10-deacetyl-2-debenzoyl-2-tigloxycanthin III of example 1;
FIG. 4 is 10-deacetyl-2-debenzoyl-2-tigloxycanthin III from example 11H NMR spectrum;
FIG. 5 is 10-deacetyl-2-debenzoyl-2-tigloxycanthin III from example 113C NMR spectrum.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings.
Example 1: a baccatin III derivative is 10-deacetyl-2-debenzoyl-2-tigloxycarpin III, as shown in figure 1, and comprises the following steps:
step S1: weighing 4.0g of 10-DAB into a 250ml reaction bottle, adding 20ml of dichloromethane and 20ml of pyridine, stirring at room temperature (27 ℃) to dissolve, dropwise adding 10g of chloroformic acid-2, 2, 2-trichloroethyl ester, and reacting at room temperature for 1 h. After the reaction is finished, adding 3mol/L hydrochloric acid into the reaction liquid to neutralize the reaction liquid to acidity, then adding 50ml dichloromethane for extraction, extracting an organic phase by using a saturated sodium bicarbonate solution, and concentrating the organic phase to obtain 7.7g of a product I.
Step S2: the product I (7.7g) was dissolved in 80ml of methanol, 6ml of a methanol solution (40%) of benzyltrimethylammonium hydroxide was added dropwise in an ice-water bath (0 ℃ C.), the reaction was quenched immediately after the addition of 50ml of a saturated ammonium chloride solution, extracted with dichloromethane, the organic phase was collected and concentrated to give 6.8g of product II.
Step S3: the product II (6.8g) was dissolved in 70ml of toluene, 0.28g of 4-dimethylaminopyridine and 1.1g of tiglic acid were added, 2.8ml of N, N-diisopropylcarbodiimide were added dropwise, and the reaction was carried out in an oil bath at 40 ℃ for 48 hours. After the reaction, the reaction mixture was filtered, the filtrate was washed with dilute hydrochloric acid, sodium bicarbonate solution and water, and the organic phase was concentrated to give 10.9g of product III (oil).
Step S4: dissolving the product III (10.9g) in 110ml of methanol and 35ml of acetic acid, adding 20g of zinc powder, reacting at room temperature (15 ℃) for 2 hours, filtering the reaction solution, diluting the filtrate with 250ml of dichloromethane, adding a sodium bicarbonate solution to neutralize until no bubbles exist, washing the organic phase with water for 2 times, and concentrating. The concentrate was purified by column chromatography eluting with dichloromethane/methanol (50: 1, V/V) as the mobile phase, the product fractions were collected, concentrated and dried to give 2.2g of 10-deacetyl-2-debenzoyl-2-tigrolactoyl baccatin III with a purity of 98.5% (HPLC) and a total molar yield of 58%.
The reaction route of the preparation process is as follows:
the structure of the prepared 10-deacetyl-2-debenzoyl-2-tigroloyl baccatin III is shown as a formula (1):
as shown in fig. 2 and 3, MS spectrum of 10-deacetyl-2-debenzoyl-2-tiganoyl baccatin III in the present example, wherein its mass/charge ratio M/z is 545.3[ M + Na ═ 545.3]+,m/z＝521.3 [M-H]-The molecular weight can be inferred to be 522, consistent with the target compound.
As shown in FIG. 4, this example of 10-deacetyl-2-debenzoyl-2-tigloxycacetin III1A HNMR map wherein,1H NMR(500MHz,DMSO-d6):6.82(1H,dd,J＝13.8Hz, 6.8Hz,H23),5.21(1H,d,J＝7.1Hz,H2),5.11(1H,d,J＝4.5Hz,13-OH), 5.10(1H,d,J＝2.4Hz,10-OH),4.91(1H,s,1-OH),4.90(1H,d,J＝3.8Hz, 7-OH),4.66(1H,d,J＝2.2Hz,H5),4.60(1H,m,H13),4.14(1H,d,J＝8.2Hz, H20),4.12(1H,s,H10),4.06(1H,m,H7),3.99(1H,d,J＝8.1Hz,H20),3.70(1H,d,J＝7.1Hz,H3),2.27(1H,m,H6),2.09(3H,s,H27),2.05(2H, m,H14),1.87(3H,s,H18),1.80(3H,s,H24),1.78(3H,s,H25),1.64(1H, m,H6),1.49(3H,s,H19),0.93(3H,s,H16/H17),0.90(3H,s,H16/H17).。
as shown in FIG. 5, this example 10-deacetyl-2-debenzoyl-2-tigloxycanthin III13A CNMR map, wherein,13C NMR(125MHz,DMSO-d6):210.3,169.3,166.6, 141.4,137.3,134.4,128.5,83.7,79.9,76.8,75.4,74.2,74.1,70.8, 66.0,56.9,46.5,42.3,36.5,26.7,22.1,20.1,14.6,14.1,11.7,9.6.。
example 2
Step S1: 10.0g of 10-DAB is weighed into a 250ml reaction bottle, 100ml of dichloromethane and 70ml of pyridine are added, stirred and dissolved at room temperature (21 ℃) to be clear, 12g of chloroformic acid-2, 2, 2-trichloroethyl ester is added dropwise, and the reaction lasts for 1.5h at room temperature. After the reaction is finished, adding 3mol/L hydrochloric acid into the reaction liquid to neutralize the reaction liquid to acidity, then adding 100ml dichloromethane for extraction, extracting an organic phase by using a saturated sodium bicarbonate solution, and concentrating the organic phase to obtain a product I17.3g.
Step S2: the product I (17.3g) is dissolved in 340ml of methanol, 9ml of a methanolic solution (40%) of benzyltrimethylammonium hydroxide are added dropwise at room temperature (9 ℃), 150ml of a saturated ammonium chloride solution are added immediately after the addition to quench the reaction, the reaction is extracted with dichloromethane, the organic phase is collected and concentrated to give 14.7g of product II.
Step S3: the product II (14.7g) was dissolved in 290ml of toluene, 0.15g of 4-dimethylaminopyridine and 1.5g of tiglic acid were added, 7.3ml of N, N-diisopropylcarbodiimide were added dropwise, and the reaction was carried out in an oil bath at 80 ℃ for 24 hours. After the reaction, the reaction mixture was filtered, the filtrate was washed with dilute hydrochloric acid, sodium bicarbonate solution and water, and the organic phase was concentrated to give 22.9g of product III (oil).
Step S4: dissolving the product III (22.9g) in 140ml of methanol and 110ml of acetic acid, adding 68g of zinc powder, reacting at room temperature (23 ℃) for 0.5h, carrying out suction filtration on the reaction solution, diluting the filtrate with 500ml of dichloromethane, adding a sodium bicarbonate solution to neutralize until no bubbles exist, washing the organic phase with water for 2 times, and then concentrating. The concentrate was purified by column chromatography eluting with dichloromethane/methanol (50: 1, V/V) as the mobile phase, the product fractions were collected, concentrated and dried to give 4.8g of 10-deacetyl-2-debenzoyl-2-tigrolactoyl baccatin III with a purity of 96.9% (HPLC) and a total molar yield of 50%.
Example 3
Step S1: weighing 1.0g of 10-DAB into a 100ml reaction bottle, adding 8ml of dichloromethane and 10ml of pyridine, stirring at room temperature (29 ℃) to dissolve, dropwise adding 3.8g of chloroformic acid-2, 2, 2-trichloroethyl ester, and reacting at room temperature for 2 hours. After the reaction is finished, adding 3mol/L hydrochloric acid into the reaction solution to neutralize the reaction solution to acidity, then adding 20ml dichloromethane for extraction, extracting an organic phase by using saturated sodium bicarbonate solution, and concentrating the organic phase to obtain a product I1.9 g.
Step S2: the product I (1.9g) was dissolved in 30ml of methanol, stirred in a cold bath (6 ℃ C.), 1.9ml of a methanol solution (40%) of benzyltrimethylammonium hydroxide was added dropwise, 20ml of a saturated ammonium chloride solution was added immediately after the addition to quench the reaction, the reaction was extracted with dichloromethane, the organic phase was collected and concentrated to give 1.6g of product II.
Step S3: the product II (1.6g) was dissolved in 25ml of toluene, 0.07g of 4-dimethylaminopyridine and 0.21g of tiglic acid were added, 0.9ml of N, N-diisopropylcarbodiimide was added dropwise, and the reaction was carried out in an oil bath at 70 ℃ for 40 hours. After the reaction, the reaction mixture was filtered, the filtrate was washed with dilute hydrochloric acid, sodium bicarbonate solution and water, and the organic phase was concentrated to give 2.8g of product III (oil).
Step S4: dissolving the product III (2.8g) in 55ml of methanol and 11ml of acetic acid, adding 4.2 g of zinc powder, reacting at room temperature (22 ℃) for 1.2h, carrying out suction filtration on the reaction solution, diluting the filtrate with 50ml of dichloromethane, adding a sodium bicarbonate solution to neutralize until no bubbles exist, washing the organic phase with water for 2 times, and concentrating. The concentrate was purified by column chromatography eluting with dichloromethane/methanol (50: 1, V/V) as the mobile phase, the product fractions were collected, concentrated and dried to give 0.5g of 10-deacetyl-2-debenzoyl-2-tigrolactoyl baccatin III with a purity of 99.3% (HPLC) and a total molar yield of 52.1%.
The present embodiment is only for explaining the present invention, and it is not limited to the present invention, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present invention.
Claims (10)
1. A preparation method of a baccatin III derivative is characterized by comprising the following steps: the method comprises the following steps:
s1, dissolving 10-DAB in dichloromethane and pyridine, dropwise adding 2,2, 2-trichloroethyl chloroformate under stirring to react, adding hydrochloric acid to neutralize to acidity after the reaction is finished, adding dichloromethane to extract, extracting an organic phase with a saturated sodium bicarbonate solution, and concentrating the organic phase to obtain a product I;
s2, dissolving the product I with methanol, dropwise adding a methanol solution of benzyltrimethyl ammonium hydroxide while stirring, immediately adding a saturated ammonium chloride solution after dropwise adding, quenching the reaction, extracting with dichloromethane, collecting an organic phase, and concentrating to obtain a product II;
s3, dissolving the product II in toluene, adding 4-dimethylaminopyridine and tiglic acid, dropwise adding N, N-diisopropylcarbodiimide, stirring for reaction, after the reaction is finished, carrying out suction filtration on a reaction solution, washing a filtrate with dilute hydrochloric acid, a sodium bicarbonate solution and water respectively, and then concentrating an organic phase to obtain a product III;
s4, dissolving the product III in methanol and acetic acid, adding zinc powder, stirring for reaction, after the reaction is finished, carrying out suction filtration on the reaction solution, diluting the filtrate with dichloromethane, then adding a sodium bicarbonate solution into the filtrate for neutralization till no bubbles exist, washing the organic phase with water for 2 times, concentrating, carrying out column chromatography purification on the concentrate, collecting the product section, concentrating and drying to obtain 10-deacetyl-2-debenzoyl-2-tigloxycarpin III;
the reaction route of the preparation process is as follows:
2. the process for the preparation of baccatin III derivatives according to claim 1, wherein: in step S1, the ratio of the amount of dichloromethane to the raw material 10-DAB is 5-10V/W, the ratio of the amount of pyridine to the raw material 10-DAB is 5-10V/W, and the ratio of the amount of chloroformic acid-2, 2, 2-trichloroethyl to the raw material 10-DAB is 1.2-3.8W/W.
3. The process for the preparation of baccatin III derivatives according to claim 1, wherein: in step S1, 10-DAB is dissolved in dichloromethane and pyridine, and dropwise added with 2,2, 2-trichloroethyl chloroformate under stirring to react at the temperature of 20-30 ℃ for 1-2 h.
4. The process for the preparation of baccatin III derivatives according to claim 1, wherein: in step S2, the ratio of methanol to the product I is 10-20V/W; the ratio of the methanol solution of benzyl trimethyl ammonium hydroxide to the product I is 0.5-1.0V/W.
5. The process for the preparation of baccatin III derivatives according to claim 1, wherein: in step S2, the reaction temperature of the quenching reaction is 0-10 ℃.
6. The process for the preparation of baccatin III derivatives according to claim 1, wherein: in the step S3, the ratio of the toluene to the product II is 10-20V/W; the ratio of tiglic acid to the product II is 0.10-0.17W/W, the ratio of 4-dimethylaminopyridine to the product II is 0.01-0.05W/W, and the ratio of N, N-diisopropylcarbodiimide to the product II is 0.4-0.6V/W.
7. The process for the preparation of baccatin III derivatives according to claim 1, wherein: in step S3, the reaction temperature of the stirring reaction is 40-60 ℃, and the reaction time of the stirring reaction is 24-48 h.
8. The process for the preparation of baccatin III derivatives according to claim 1, wherein: in step S4, the ratio of methanol to the product III is 6-20V/W, and the ratio of acetic acid to the product III is 3-5V/W; the ratio of the zinc powder to the product III is 1.5-3W/W.
9. The process for the preparation of baccatin III derivatives according to claim 1, wherein: in step S4, the reaction temperature of the stirring reaction is 15-25 ℃, and the reaction time of the stirring reaction is 0.5-2 h.
10. A baccatin III derivative prepared by the process for preparing a baccatin III derivative according to any one of claims 1-9, wherein: the baccatin III derivative is 10-deacetyl-2-debenzoyl-2-tigrolyl baccatin III, and the structure of the baccatin III derivative is shown as a formula (1):
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010440959.2A CN111533714B (en) | 2020-05-22 | 2020-05-22 | Baccatin III derivative and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010440959.2A CN111533714B (en) | 2020-05-22 | 2020-05-22 | Baccatin III derivative and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111533714A true CN111533714A (en) | 2020-08-14 |
| CN111533714B CN111533714B (en) | 2023-04-11 |
Family
ID=71972261
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010440959.2A Active CN111533714B (en) | 2020-05-22 | 2020-05-22 | Baccatin III derivative and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111533714B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620911A (en) * | 2021-09-14 | 2021-11-09 | 无锡紫杉药业有限公司 | Paclitaxel derivative and preparation method thereof |
| CN115326970A (en) * | 2022-08-17 | 2022-11-11 | 上海卓鼎生物技术有限公司 | Detection method of 7-Troc-baccatin III-13-O-oxazoline carboxylate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006108561A1 (en) * | 2005-04-12 | 2006-10-19 | Indena S.P.A | A process for the purification of 10-deacetylbaccatine iii from 10-de acet yl-2- debenzoyl-2-pentenoylbaccatine iii |
| CN110078686A (en) * | 2019-04-28 | 2019-08-02 | 云南汉德生物技术有限公司 | The method of 10- deacetylate Bakating III synthesis Cabazitaxel |
| CN110407775A (en) * | 2019-08-22 | 2019-11-05 | 江苏红豆杉药业有限公司 | A kind of preparation method of taxanes natural products |
-
2020
- 2020-05-22 CN CN202010440959.2A patent/CN111533714B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006108561A1 (en) * | 2005-04-12 | 2006-10-19 | Indena S.P.A | A process for the purification of 10-deacetylbaccatine iii from 10-de acet yl-2- debenzoyl-2-pentenoylbaccatine iii |
| CN110078686A (en) * | 2019-04-28 | 2019-08-02 | 云南汉德生物技术有限公司 | The method of 10- deacetylate Bakating III synthesis Cabazitaxel |
| CN110407775A (en) * | 2019-08-22 | 2019-11-05 | 江苏红豆杉药业有限公司 | A kind of preparation method of taxanes natural products |
Non-Patent Citations (4)
| Title |
|---|
| BRUNO GABETTA ET AL: "10-DEACETYLBACCATIN III ANALOGUES FROM TAXUS BACCATA", 《JOURNAL OF NATURAL PRODUCTS》 * |
| BRUNO GABETTA ET AL: "Paclitaxel Analogues from Taxus × media cv.Hicksii", 《J.NAT.PROD.》 * |
| EDWARD H.KERNS ET AL: "Profiling New Taxanes Using LC/MS and LC/MS/MS Substructural Analysis Techniques", 《RAPID COMMUNICATIONS IN MASS SPECTROMETRY》 * |
| 审查员: "171926-87-7", 《STN检索报告》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620911A (en) * | 2021-09-14 | 2021-11-09 | 无锡紫杉药业有限公司 | Paclitaxel derivative and preparation method thereof |
| CN115326970A (en) * | 2022-08-17 | 2022-11-11 | 上海卓鼎生物技术有限公司 | Detection method of 7-Troc-baccatin III-13-O-oxazoline carboxylate |
| CN115326970B (en) * | 2022-08-17 | 2024-03-29 | 上海卓鼎生物技术有限公司 | Detection method of 7-Troc-baccatin III-13-O-oxazoline carboxylic ester |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111533714B (en) | 2023-04-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69834584T2 (en) | Process for the selective derivatization of taxanes | |
| CN111533714B (en) | Baccatin III derivative and preparation method thereof | |
| CN110407775B (en) | Preparation method of taxane natural product | |
| CA2310778C (en) | Intermediates and methods useful in the semisynthesis of paclitaxel and analogs | |
| KR101329902B1 (en) | A process for the purification of 10-deacetylbaccatine ⅲ from 10-deacetyl-2-debenzoyl-2-pentenoylbaccatine ⅲ | |
| DE60103560T2 (en) | PROCESS FOR PRODUCING PACLITAXEL | |
| CN113620911A (en) | Paclitaxel derivative and preparation method thereof | |
| CN103130753A (en) | Semi-synthesis method of antitumor drug taxol | |
| KR100921036B1 (en) | Method of preparing taxane derivatives and intermediates used therein | |
| CN113773282A (en) | Preparation method of 10-acetyl paclitaxel | |
| CN107141272A (en) | A kind of semi-synthetic docetaxel method and its intermediate | |
| AU2002234535A1 (en) | A process for the preparation of paclitaxel | |
| CN106632160A (en) | Methods for preparing semi-synthetic paclitaxel and intermediate thereof | |
| CN101448839B (en) | A process for the preparation of a taxane derivative | |
| CN110317183B (en) | Method for purifying natural extract product of taxus chinensis | |
| CN110746382B (en) | Cabazitaxel precursor derivative and synthesis method and application thereof | |
| KR101379694B1 (en) | Method for preparing taxane derivatives | |
| CA2672911C (en) | Semi-synthetic process for the preparation of taxane derivatives | |
| CA2538860A1 (en) | Conversion 9-dihydro-13-acetylbaccatin iii to 10-deacetylbaccatin iii | |
| CN115215830A (en) | C-8 hydroxyl substituted brazilein analogue and preparation method and application thereof | |
| CN115197176A (en) | Preparation method of 7-trichloroethoxycarbonyl docetaxel | |
| CN113354696A (en) | Preparation method of 7-xylosyl paclitaxel | |
| EP2091931A2 (en) | A process for the preparation of secotaxanes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |