CN1962664A - 2,4-modified 1-dehydroxy baccatin VI derivative and its preparation method - Google Patents
2,4-modified 1-dehydroxy baccatin VI derivative and its preparation method Download PDFInfo
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Abstract
The invention discloses a new synthesizing method of 2, 4-position-1-dehydroxy palmatine VI derivant in the drug technical domain, which is characterized by the following: decorating C2 benzoyl and C4 acetyl of 4, 9, 10-trideacetyl-4-(3-carbonyl) butyric-2-debenzoyl-2-substituted aromatic formyl-9, 10-O-isopropylidene-1-dehydroxy palmatine VI; synthesizing new derivant.
Description
Technical field
The present invention relates to novel 2; the 1-dehydroxy baccatin VI derivative 4 of 4 modifications; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI and 4,9,10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI and preparation method thereof belongs to the organic synthesis technical field of pharmaceuticals.
Background technology
Taxol (Paclitaxel, trade(brand)name Taxol) is a kind of new antitumor drug of separation and Extraction from Taxus (Taxus) plant, gone on the market by the new drug of U.S. FDA official approval the end of the year 1992 for treatment ovarian cancer and mammary cancer with unique antitumour activity.Its novel structure, mechanism of action uniqueness, active strong, action spectrum is wide, through clinical proof taxol is the specific medicament of more than 10 kind of cancers such as treatment mammary cancer, uterus carcinoma, carcinoma of the pancreas and colorectal carcinoma, lung cancer, liver cancer, incidence cancer, soft tissue cancer, gastrointestinal cancer, cervical cancer, cns tumor, melanoma and leukemia cell etc. to the people have cytotoxicity, are one of best antitumor drugs of generally acknowledging in the world in recent years.But all the time, the development of taxol is subjected to the puzzlement of two subject matters: the one, and the very little and reason such as restriction collection etc. of its natural content can not satisfy the needs of clinical and fundamental research far away.The 2nd, problems such as taxol soluble is extremely low, resistance, toxic side effect also are the very big obstacles of its clinical application.So cause the section that multi-disciplinary investigator is relevant to taxol
The concern of and technical problem, wherein the research of the new resources of taxol and analogue thereof receives much attention, and has promoted the relevant progress of research of taxanes family greatly.With higher Taxan two terpene components (Taxoids) of content is that semi-synthetic taxol of precursor and derivative thereof are to solve shortage of resources and improve one of main path of over-all properties.The 1-dehydroxy baccatin VI is the content height in beautiful Ramulus et folium taxi cuspidatae, and has kept the ring skeleton and the necessary functional group of Taxan diterpene, so select for use it to carry out structural modification as semi-synthetic precursor or to it, has certain social meaning and economic implications.
Studies show that 2-benzoyl and 4-ethanoyl are the important group of keeping its physiologically active on the taxol parent.2 benzoyls and the formed recessed steric configuration to the hole of C13 side chain are even more important to the taxol antitumour activity.The part substituting group can increase its physiologically active effectively.Therefore, some research groups are devoted to the structural modification to 2 benzoyls and 4 ethanoyl on the taxol parent.People such as Chen adopt the BMS method
[2,3]Carry out the C2 structural modification, Kingston
[4,5]Methods such as employing phase-transfer catalyst are sloughed 2 benzoyl.
In the present invention; we have designed a synthetic route that selectivity is strong, simple to operate; realize the structural modification of 1-dehydroxy baccatin VI derivative C2 benzoyl and C4 ethanoyl; synthesizing new derivative 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI and 4; 9; 10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI.
Summary of the invention
The purpose of this invention is to provide novel 2; the 1-dehydroxy baccatin VI derivative of 4 modifications is 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI and 4; 9,10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI and preparation method thereof.
A kind of novel 1-dehydroxy baccatin VI derivative of the present invention is 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9, and 10-O-isopropylidene-1-dehydroxy baccatin VI is characterized in that having following structural formula:
A kind of novel 1-dehydroxy baccatin VI derivative of the present invention is 4; 9; 10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9, and 10-O-isopropylidene-1-dehydroxy baccatin VI is characterized in that having following molecular formula and structural formula:
Above-mentioned 1-dehydroxy baccatin VI derivative is 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI or 4; 9; 10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9, and the preparation method of 10-O-isopropylidene-1-dehydroxy baccatin VI is characterized in that having following processing step:
A. add a certain amount of 1-dehydroxy baccatin VI 1 and hydrazine hydrate in reaction vessel, and add etoh solvent, stirring at room makes to react completely; With hydrochloric acid neutralization, ethyl acetate extraction, anhydrous sodium sulfate drying is used in organic layer washing three times, removes solvent under reduced pressure.Crude product gets colourless transparent crystal 4,7,9,10,13-five deacetylates-1-dehydroxy baccatin VI 2 with ethyl acetate and normal hexane mixed solvent recrystallization;
B. a certain amount of compound 2 is dissolved in the mixed solvent, add catalyzer (choosing any one kind of them in camphorsulfonic acid, polynite K10, the tosic acid pyridine), stirring at room, add a certain amount of 2 again, the 2-Propanal dimethyl acetal, add the saturated sodium bicarbonate solution neutralization after reacting completely, use anhydrous magnesium sulfate drying after the organic layer washed several times with water, underpressure distillation removes and desolvates, and crude product gets white solid 4,7 with column chromatography purification, 9,10,13-five deacetylates-9,10-O-isopropylidene-1-dehydroxy baccatin VI 3;
C. under nitrogen protection, compound 3 is dissolved in the tetrahydrofuran (THF), add lithium aluminum hydride or 2-(2-methoxyl group-oxyethyl group) sodium aluminum hydride under the room temperature, add the saturated ammonium chloride solution neutralization after reacting completely, suction filtration is removed white gelatinous precipitate, filtrate is also washed repeatedly with ethyl acetate extraction, remove solvent behind the anhydrous magnesium sulfate drying under reduced pressure, head product gets white solid 4 with re-crystallizing in ethyl acetate, 7,9,10,13-five deacetylates-2-removes benzoyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 4;
D. a certain amount of compound 4 is dissolved in the tetrahydrofuran (THF), adds a certain amount of dimethylamino pyridine or 4-pyrroles's pyridine, add a certain amount of diacetyl oxide again, stirring at room makes to react completely; Add an amount of water and use ethyl acetate extraction, organic layer washed several times with water, anhydrous magnesium sulfate drying, remove solvent under reduced pressure, head product gets white solid 4,7 through column chromatography for separation, 9,10-four deacetylates-2-removes benzoyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 5;
E. compound 5 is dissolved in the toluene, add dimethylamino pyridine or 4-pyrroles's pyridine under the room temperature and replace aromatic acid, stir, add the dicyclohexyl carbimide again, add an amount of ethanol after reacting completely, remove under reduced pressure behind the solvent with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times; The organic layer washing is also used anhydrous magnesium sulfate drying, removes solvent under reduced pressure, and head product gets white solid 4,7,9 through column chromatography purification, and 10-four deacetylates-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 6;
F. compound 6 is dissolved in the toluene, adding dimethylamino pyridine or 4-pyrroles's pyridine and diacetyl oxide under specified temp stirs, add the dicyclohexyl carbimide again, continue to be stirred to and react completely, remove solvent under reduced pressure after adding an amount of methyl alcohol, with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times; Organic layer washing is also used anhydrous magnesium sulfate drying, removes solvent under reduced pressure, head product with silica gel column chromatography separate white solid 4,9,10-three deacetylates-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 7;
G. compound 7 is dissolved in the toluene, adding dimethylamino pyridine or 4-pyrroles's pyridine and diacetyl oxide or propionic anhydride at a certain temperature stirs, add the dicyclohexyl carbimide again, continue to be stirred to and react completely, remove solvent under reduced pressure after adding an amount of methyl alcohol, with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times; The organic layer washing is also used anhydrous magnesium sulfate drying; remove solvent under reduced pressure; head product with silica gel column chromatography separate white solid 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 8 or 4,9; 10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 9.
Building-up process of the present invention is as follows:
The characteristics of building-up reactions of the present invention are: the selectivity deacetylation of (1) 1-dehydroxy baccatin VI; (2) 9,10 of compound 2 hydroxyl selective protections; (3) 13 of compound 3 hydroxyl highly selective acylation reactions; (4) 2 of compound 5 hydroxyl selectively acylating reactions; (5) 7 of compound 4 hydroxyl selective protections; (6) on 4 hydroxyls of compound 5, introduce 3-carbonyl butyryl radicals or 2-methyl-3-carbonyl pentanoyl.
The advantage of the inventive method is raw material 1-dehydroxy baccatin VI content height in beautiful Ramulus et folium taxi cuspidatae, and is easily separated; Easy and simple to handle; Selectivity is good and productive rate is high.
Embodiment
After now specific embodiments of the invention being described in.
Embodiment 1
4,9,10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-removes benzoyl bromide between benzoyl-2--9, the concrete synthesis step of 10-O-isopropylidene-1-dehydroxy baccatin VI 8:
A.1-(279.2mg 0.4mmol) is dissolved in 16 mL, 95% ethanol dehydroxy baccatin VI 1, adds the 16mL hydrazine hydrate, and stirring at room makes to react completely.With the neutralization of 0.2N hydrochloric acid, ethyl acetate extraction, anhydrous sodium sulfate drying is used in organic layer washing three times, removes solvent under reduced pressure.Crude product gets colourless transparent crystal 4,7,9,10 with ethyl acetate and normal hexane mixed solvent recrystallization, and 13-five deacetylates-1-dehydroxy baccatin VI 2, productive rate are 92%.B. compound 2 (107.4mg; 0.22mmol) be dissolved in 9mL methylene dichloride and the 0.4mL methyl alcohol; the dissolving back adds 2 fully; (0.33mL's 2-Propanal dimethyl acetal 2.64mmol), stirs; add the 10.8mg camphorsulfonic acid again; add the saturated sodium bicarbonate solution neutralization after reacting completely, use anhydrous magnesium sulfate drying after the organic layer washed several times with water, underpressure distillation removes and desolvates; the crude product re-crystallizing in ethyl acetate; get white solid 4,7,9; 10; 13-five deacetylates-9,10-O-isopropylidene-1-dehydroxy baccatin VI 3 112.7mg, productive rate is 97%.
C. under nitrogen protection; with compound 3 (369.6mg; 0.7mmol) be dissolved in the 14 mL tetrahydrofuran (THF)s; add lithium aluminum hydride (0.106mg under the room temperature; 2.8mmol), TLC follows the tracks of reaction, reacts completely to add the saturated ammonium chloride solution neutralization; suction filtration is removed white gelatinous precipitate; filtrate is also washed repeatedly with ethyl acetate extraction, removes solvent behind the anhydrous magnesium sulfate drying under reduced pressure, and head product gets white solid 4 with re-crystallizing in ethyl acetate; 7; 9,10,13-five deacetylates-2-removes benzoyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI 4 276.7mg, productive rate is 93%.
D. (212.5mg 0.5mmol) is dissolved in the 10mL tetrahydrofuran (THF) compound 4, adds the dimethylamino pyridine of catalytic amount, and (0.25mL, 2.5mmol), stirring at room makes to react completely to add diacetyl oxide again.Add an amount of water and use ethyl acetate extraction; the organic layer washed several times with water; anhydrous magnesium sulfate drying; remove solvent under reduced pressure, head product gets white solid 4,7 through column chromatography for separation; 9; 10-four deacetylates-2-removes benzoyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 5 228.8mg, and productive rate is 98%.
E. (93.4mg 0.2mmol) is dissolved in the 2mL toluene compound 5, adds dimethylamino pyridine (73.3mg under the room temperature, 0.6mmol) and m-bromobenzoic acid (120.6mg, 0.6mmol) stir, add again the dicyclohexyl carbimide (123.6mg, 0.6mmol), add an amount of ethanol after reacting completely, remove under reduced pressure behind the solvent with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out suction filtration, filtrate concentrates, repeatedly for several times.The organic layer washing is also used anhydrous magnesium sulfate drying, removes solvent under reduced pressure, and head product gets white solid 4 through column chromatography purification; 7,9,10-four deacetylates-2-removes benzoyl bromide between benzoyl-2--9; 10-O-isopropylidene-1-dehydroxy baccatin VI 6 115.7mg, productive rate is 89%.
F. (80.0mg 0.123mmol) is dissolved in the 2.5mL toluene compound 6, adds dimethylamino pyridine (45.0mg, 0.368mmol) and diacetyl oxide (0.14mL 1.4mmol) stirs, and adds dicyclohexyl carbimide (76.0mg again, 0.369mmol), continue to be stirred to and react completely, remove solvent under reduced pressure after adding an amount of methyl alcohol, with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times.Organic layer washing is also used anhydrous magnesium sulfate drying, removes solvent under reduced pressure, head product with silica gel column chromatography separate white solid 4; 9; 10-three deacetylates-2-removes benzoyl bromide between benzoyl-2--9,10-O-isopropylidene-1-dehydroxy baccatin VI 7 72.2mg, and productive rate is 85%.
G. (69.0mg 0.1mmol) is dissolved in the toluene compound 7, adds dimethylamino pyridine (183.2mg at a certain temperature, 1.5mmol) and diacetyl oxide (0.2mL 2.0mmol) stirs, and adds dicyclohexyl carbimide (309.2mg again, 1.5mmol), continue to be stirred to and react completely, remove solvent under reduced pressure after adding an amount of methyl alcohol, with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times.The organic layer washing is also used anhydrous magnesium sulfate drying; remove solvent under reduced pressure; head product with silica gel column chromatography separate white solid 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-removes benzoyl bromide between benzoyl-2--9; 10-O-isopropylidene-1-dehydroxy baccatin VI 8 51.1mg, productive rate is 66%.
Embodiment 2
4,9,10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-removes benzoyl bromide between benzoyl-2--9, the concrete synthesis step of 10-O-isopropylidene-1-dehydroxy baccatin VI 9:
Steps A-F is that the synthesis step of compound 8 is just the same in present embodiment and the foregoing description 1, and that different is step G.
G. (69.0mg 0.1mmol) is dissolved in the toluene compound 7, adds dimethylamino pyridine (183.2mg at a certain temperature, 1.5mmol) and propionic anhydride (0.26mL 2.0mmol) stirs, and adds dicyclohexyl carbimide (309.2mg again, 1.5mmol), continue to be stirred to and react completely, remove solvent under reduced pressure after adding an amount of methyl alcohol, with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times.The organic layer washing is also used anhydrous magnesium sulfate drying; remove solvent under reduced pressure; head product with silica gel column chromatography separate white solid 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-removes benzoyl bromide between benzoyl-2--9; 10-O-isopropylidene-1-dehydroxy baccatin VI 9 53.0mg, productive rate is 66%.
Claims (3)
1. one kind novel 2; the 1-dehydroxy baccatin VI derivative of 4 modifications is 4,9, and 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI is characterized in that having following molecular structural formula:
2. one kind novel 2; the 1-dehydroxy baccatin VI derivative of 4 modifications is 4; 9; 10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI is characterized in that having following molecular structural formula:
R is a substituted aryl.
3. claim 1 or 2 described 1-dehydroxy baccatin VI derivatives are 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9; 10-O-isopropylidene-1-dehydroxy baccatin VI or 4; 9; 10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9, and the preparation method of 10-O-isopropylidene-1-dehydroxy baccatin VI is characterized in that having following processing step:
A. add a certain amount of 1-dehydroxy baccatin VI 1 and hydrazine hydrate in reaction vessel, and add etoh solvent, stirring at room makes to react completely; With hydrochloric acid neutralization, ethyl acetate extraction, anhydrous sodium sulfate drying is used in organic layer washing three times, removes solvent under reduced pressure; Crude product gets colourless transparent crystal 4,7,9,10,13-five deacetylates-1-dehydroxy baccatin VI 2 with ethyl acetate and normal hexane mixed solvent recrystallization;
B. a certain amount of compound 2 is dissolved in the mixed solvent, add catalyzer (choosing any one kind of them in camphorsulfonic acid, polynite K10, the tosic acid pyridine), stirring at room, add a certain amount of 2 again, the 2-Propanal dimethyl acetal, add the saturated sodium bicarbonate solution neutralization after reacting completely, use anhydrous magnesium sulfate drying after the organic layer washed several times with water, underpressure distillation removes and desolvates, and crude product gets white solid 4,7 with column chromatography purification, 9,10,13-five deacetylates-9,10-O-isopropylidene-1-dehydroxy baccatin VI 3;
C. under nitrogen protection, compound 3 is dissolved in the tetrahydrofuran (THF), add lithium aluminum hydride or 2-(2-methoxyl group-oxyethyl group) sodium aluminum hydride under the room temperature, add the saturated ammonium chloride solution neutralization after reacting completely, suction filtration is removed white gelatinous precipitate, filtrate is also washed repeatedly with ethyl acetate extraction, remove solvent behind the anhydrous magnesium sulfate drying under reduced pressure, head product gets white solid 4 with re-crystallizing in ethyl acetate, 7,9,10,13-five deacetylates-2-removes benzoyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 4;
D. a certain amount of compound 4 is dissolved in the tetrahydrofuran (THF), adds a certain amount of dimethylamino pyridine or 4-pyrroles's pyridine, add a certain amount of diacetyl oxide again, stirring at room makes to react completely; Add an amount of water and use ethyl acetate extraction, organic layer washed several times with water, anhydrous magnesium sulfate drying, remove solvent under reduced pressure, head product gets white solid 4,7 through column chromatography for separation, 9,10-four deacetylates-2-removes benzoyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 5;
E. compound 5 is dissolved in the toluene, adding dimethylamino pyridine or 4-ratio under the room temperature coughs up pyridine and replaces aromatic acid, stir, add the dicyclohexyl carbimide again, add an amount of ethanol after reacting completely, remove under reduced pressure behind the solvent with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times; The organic layer washing is also used anhydrous magnesium sulfate drying, removes solvent under reduced pressure, and head product gets white solid 4,7,9 through column chromatography purification, and 10-four deacetylates-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 6;
F. compound 6 is dissolved in the toluene, under specified temp, add dimethylamino pyridine or the 4-ratio coughs up pyridine and diacetyl oxide stirs, add the dicyclohexyl carbimide again, continue to be stirred to and react completely, remove solvent under reduced pressure after adding an amount of methyl alcohol, with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times; Organic layer washing is also used anhydrous magnesium sulfate drying, removes solvent under reduced pressure, head product with silica gel column chromatography separate white solid 4,9,10-three deacetylates-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 7;
G. compound 7 is dissolved in the toluene, adding dimethylamino pyridine or 4-ratio at a certain temperature coughs up pyridine and diacetyl oxide or propionic anhydride and stirs, add the dicyclohexyl carbimide again, continue to be stirred to and react completely, remove solvent under reduced pressure after adding an amount of methyl alcohol, with acetic acid ethyl dissolution and leave standstill, the cotton-shaped solid of adularescent is separated out, suction filtration, filtrate concentrates, repeatedly for several times; The organic layer washing is also used anhydrous magnesium sulfate drying; remove solvent under reduced pressure; head product with silica gel column chromatography separate white solid 4; 9; 10-three deacetylates-4-(3-carbonyl) butyryl radicals-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 8 or 4,9; 10-three deacetylates-4-(2-methyl-3-carbonyl) pentanoyl-2-goes benzoyl-2-to replace sweet-smelling formacyl-9,10-O-isopropylidene-1-dehydroxy baccatin VI 9.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100465170C (en) * | 2007-02-09 | 2009-03-04 | 上海大学 | Preparing method of C7, C10 substituted 1-dehydroxy baccatin VI derivative |
| CN102558105A (en) * | 2011-12-26 | 2012-07-11 | 上海大学 | 9(R)-hydrogenation-1-deoxidation taxol derivative modified by C4 and preparation method thereof |
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2006
- 2006-11-09 CN CN 200610118157 patent/CN1962664A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100465170C (en) * | 2007-02-09 | 2009-03-04 | 上海大学 | Preparing method of C7, C10 substituted 1-dehydroxy baccatin VI derivative |
| CN102558105A (en) * | 2011-12-26 | 2012-07-11 | 上海大学 | 9(R)-hydrogenation-1-deoxidation taxol derivative modified by C4 and preparation method thereof |
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