CN103880866A - Navelbine tartrate derivative and preparation method thereof - Google Patents
Navelbine tartrate derivative and preparation method thereof Download PDFInfo
- Publication number
- CN103880866A CN103880866A CN201210559799.9A CN201210559799A CN103880866A CN 103880866 A CN103880866 A CN 103880866A CN 201210559799 A CN201210559799 A CN 201210559799A CN 103880866 A CN103880866 A CN 103880866A
- Authority
- CN
- China
- Prior art keywords
- vinorelbine tartrate
- phase
- volume ratio
- preparation
- high performance
- 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
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention relates to a navelbine tartrate derivative and a preparation method thereof, and belongs to the field of chemical pharmacy. Navelbine tartrate is taken as the initiator, then the navelbine tartrate is subjected to a series of separation and purification treatments, finally a novel compound is obtained, and the novel compound is identified as 6'-N-methyl-17-bromonavelbine tartrate. The preparation method of high performance liquid chromatography (HPLC) of the novel compound has the advantages of simple conditions, convenient operation, and rapid and accurate identification result. The novel compound 6'-N-methyl-17-bromonavelbine tartrate is provided as a reference for synthesis mechanism of navelbine tartrate.
Description
Technical field
The present invention relates to chemical pharmacy field, especially relate to a kind of vinorelbine tartrate derivative and preparation method thereof.
Background technology
High performance liquid chromatography (High Performance Liquid Chromatography/HPLC) claims again " high pressure liquid chromatography ", " high-speed liquid chromatography ", " high separation liquid chromatography ", " column chromatography in modern age " etc.High performance liquid chromatography is a chromatographic important branch, taking liquid as moving phase, adopt high pressure transfusion system, to there is the single solvent of opposed polarity or the moving phase such as mixed solvent, damping fluid of different ratios pumps into the chromatographic column that stationary phase is housed, in post each composition separated after, enter detector and detect, thereby realize the analysis to sample.The method has become important separate analytical technique in the ambits such as chemistry, medical science, industry, agronomy, commodity inspection and method inspection.
Tlc (TLC), is that suitable stationary phase is coated on sheet glass, plastics or aluminium substrate, becomes an even thin layer.Until point sample, launch after, according to Rf value (Rf) and suitable contrast by the same method the Rf value of the color atlas of gained (Rf) compare, in order to carry out the method for discriminating, determination of foreign matter or assay of medicine.Tlc is a kind of very important experimental technique of sharp separation and a small amount of material of qualitative analysis, also for following the tracks of reaction process.
Vinorelbine tartrate is semi-synthetic by vinealeucoblastine(VLB), on vincaleucoblastine ring, carry out chemically modified, nonatomic ring is become to octatomic ring, caused this product to there is stronger lipotropy, the higher confining force of organizing, make its scope of application, toxicity different from vinealeucoblastine(VLB), the vincristine(VCR) etc. of clinical application.Vinorelbine tartrate antitumour activity is high, and antitumor spectra is wide, and through external clinical study, single medicine or drug combination treatment nonsmall-cell lung cancer, mammary cancer, ovarian cancer, malignant lymphoma etc., shown outstanding curative effect.It is similar to the effect of mitotic division microtubule and vincaleucoblastine, vincristine(VCR), but to the effect of neural axis microtubule compared with vincristine(VCR) and vincaleucoblastine a little less than, thereby its antitumor action is strong, and to change relevant neurotoxicity lower with axon microtubule.Described vinorelbine tartrate structural formula is:
Summary of the invention
The present invention proposes the auspicious shore of a kind of tartrate derivative and preparation method thereof, the present invention adopts high performance liquid chromatography preparation method to obtain and identifies new compound 6'-N-methyl-17-bromo vinorelbine tartrate, this preparation method condition is simple, easy to operate, and result certification accurately and fast.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
A preparation method for vinorelbine tartrate derivative, is characterized in that, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, and carry out gradient elution with eluent;
B, detect with thin-layer chromatography, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared at 16min and obtains 6'-N-methyl-17-bromo vinorelbine tartrate by high performance liquid chromatography.
Preferably, it further comprises step c: 6'-N-methyl-17-bromo vinorelbine tartrate that in described step b, high performance liquid chromatography prepares is carried out to mass spectrum and proton nmr spectra detection.
Preferably, in described step a, normal phase silicagel column granularity is 200～300 orders, and in described step a, eluent is chloroform-methanol system, and the volume ratio of described chloroform-methanol system is 100:1-1:1.
Preferably, in described step b, high performance liquid chromatography preparation method's mobile phase A is acetonitrile mutually, and B is diethylamine-purified water mutually, and described B mutually middle diethylamine-purified water volume ratio is 14:986, and described A phase and described B phase volume ratio are A:B=50:50.
A method of purification for vinorelbine tartrate derivative, is characterized in that, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, and carry out gradient elution with eluent;
B, detect with thin-layer chromatography, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared at 16min and obtains 6'-N-methyl-17-bromo vinorelbine tartrate by high performance liquid chromatography.
Preferably, it further comprises step c: 6'-N-methyl-17-bromo vinorelbine tartrate that in described step b, high performance liquid chromatography prepares is carried out to mass spectrum and proton nmr spectra detection.
Preferably, in described step a, normal phase silicagel column granularity is 200～300 orders, and in described step a, eluent is chloroform-methanol system, and the volume ratio of described chloroform-methanol system is 100:1-1:1.
Preferably, in described step b, high performance liquid chromatography preparation method's mobile phase A is acetonitrile mutually, and B is diethylamine-purified water mutually, and described B mutually middle diethylamine-purified water volume ratio is 14:986, and described A phase and described B phase volume ratio are A:B=50:50.
A kind of vinorelbine tartrate derivative, is characterized in that, the structural formula of described 6'-N-methyl-17-bromo vinorelbine tartrate is:
Described 6'-N-methyl-17-bromo vinorelbine tartrate provides reference for the mechanism of vinorelbine tartrate synthesis technique.
Preferably, described 6'-N-methyl-17-bromo vinorelbine tartrate is detected and is drawn its structural formula by mass spectrum and proton nmr spectra.
The invention has the beneficial effects as follows: the present invention, taking vinorelbine tartrate as initiator, obtains and identify new compound 6'-N-methyl-17-bromo vinorelbine tartrate by a series of separation and purification means, and the present invention has following beneficial effect:
1, analyzed vinorelbine tartrate related derivatives by 6'-N-methyl-17-bromo vinorelbine tartrate and produced possible condition, for the quality control such as technology controlling and process and sample retention provides foundation.
2, set up vinorelbine tartrate related derivatives high performance liquid chromatography preparation method, for the qualification of vinorelbine tartrate derivative provides strong reference.
3, according to the structure of 6'-N-methyl-17-bromo vinorelbine tartrate, for the mechanism of vinorelbine tartrate synthesis technique provides reference.
Brief description of the drawings
Fig. 1 is the embodiment of the present invention 3 unresolvable tartaric acid vinorelbine high performance liquid phase spectrograms;
Fig. 2 is 16min vinorelbine tartrate derivative high performance liquid phase collection of illustrative plates in the embodiment of the present invention 3;
Fig. 3 is 16min vinorelbine tartrate derivative in the embodiment of the present invention 3
1h-NMR collection of illustrative plates;
Fig. 4 is 16min vinorelbine tartrate derivative ESI-MS collection of illustrative plates in the embodiment of the present invention 3;
Embodiment
Example of the present invention is can not limit the present invention to explanation of the present invention, and any change and adjustment in implication and the scope suitable with the present invention, all should think within the scope of the invention.
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1
A preparation method for vinorelbine tartrate derivative, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, and carry out gradient elution with eluent;
B, detect by tlc, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared to obtain to 16min vinorelbine tartrate derivative by high performance liquid chromatography;
In the present embodiment, described vinorelbine tartrate is the vinorelbine tartrate crude product after synthesizing.Described vinorelbine tartrate is concentrated, and what select is that Rotary Evaporators concentrates, and described Rotary Evaporators model is EYELA-N-1000, treats that the solvent in described vinorelbine tartrate has concentrated, and obtains paste.
In the present embodiment, the granularity of normal phase silicagel column is chosen as < 100 orders, 100～200 orders, 200～300 orders or 300～400 orders; When the granularity of described normal phase silicagel column is < 100 order, it is not suitable for normal pressure post, therefore cannot apply in the present embodiment; When the granularity of described normal phase silicagel column is 100～200 order, the separating effect of silica gel is very bad, has assorted spot to occur, the effect that therefore cannot reach in this enforcement; When the granularity of described normal phase silicagel column is 300～400 order, flow velocity can be very slow, affects experiment process; Therefore in the present embodiment, the granularity of preferred described normal phase silicagel column is 200～300 orders.
Conventional eluent can be selected sherwood oil-acetone, petroleum ether-ethyl acetate or chloroform-methanol, owing to selecting described sherwood oil-acetone and petroleum ether-ethyl acetate as eluent, experiment effect is very undesirable, therefore preferably chloroform-methanol system of eluent described in the present embodiment, the volume ratio of described chloroform and methyl alcohol is 100:1-1:1.
In described step b, high performance liquid chromatography preparation method's mobile phase A phase and B phase determines, inspection method to vinealeucoblastine(VLB) in the Pharmacopoeia of the People's Republic of China that can publish with reference to Chinese Pharmacopoeia Commission in 2010, determine that A is acetonitrile mutually, B is diethylamine-purified water mutually, and simultaneously determine described B mutually in diethylamine-purified water volume ratio be 14:986.
Described A phase is 30:70 with the volume ratio of described B phase in the present embodiment.
High performance liquid chromatography (HPLC) preparation condition used in the present embodiment is:
Column length and model: SinoChrom ODS AP, 10 μ m; Column temperature: 30 DEG C, high performance liquid chromatography preparation method's mobile phase A is acetonitrile mutually, and B is diethylamine-purified water (volume ratio 14:986), wherein volume ratio A:B=30:70 mutually; Flow velocity: 3ml/min, detects wavelength: 267nm.
Detect preparing gained 16min vinorelbine tartrate derivative by high performance liquid chromatography, find all peaks stack and overlapping, cannot effectively detect described 16min vinorelbine tartrate derivative.
Embodiment 2
A preparation method for vinorelbine tartrate derivative, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, described normal phase silicagel column granularity is 200～300 orders, and carries out gradient elution by chloroform-methanol system, and described chloroform-methanol system volume ratio is 100:1-1:1;
B, detect by tlc, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared by high performance liquid chromatography, mobile phase A is acetonitrile mutually, B is diethylamine-purified water mutually, described B mutually middle diethylamine-purified water volume ratio is 14:986, and the volume ratio of described A phase and B phase is 40:60, preparation 16min vinorelbine tartrate derivative;
Detect preparing the auspicious derivative in gained 16min tartrate Changchun by high performance liquid chromatography, find all peaks stack and overlapping, cannot effectively detect described 16min vinorelbine tartrate derivative.
Embodiment 3
A preparation method for vinorelbine tartrate derivative, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, described normal phase silicagel column granularity is 200～300 orders, and carries out gradient elution by chloroform-methanol system, and described chloroform-methanol system volume ratio is 100:1-1:1;
B, detect by tlc, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared by high performance liquid chromatography, mobile phase A is acetonitrile mutually, B is diethylamine-purified water mutually, described B mutually middle diethylamine-purified water volume ratio is 14:986, and the volume ratio of described A phase and B phase is 50:50, preparation 16min vinorelbine tartrate derivative;
C, the derivative that in described step b, high performance liquid chromatography prepares is carried out to mass spectrum and proton nmr spectra detect, described detected result is analyzed and structural confirmation; Through confirming, described 16min vinorelbine tartrate derivative is new compound, called after 6'-N-methyl-17-bromo vinorelbine tartrate.
Detect preparing the auspicious derivative in gained 16min tartrate Changchun by high performance liquid chromatography, Fig. 1 is the embodiment of the present invention 3 unresolvable tartaric acid vinorelbine high performance liquid phase spectrograms; Fig. 2 is 16min vinorelbine tartrate derivative high performance liquid phase collection of illustrative plates in the embodiment of the present invention 3; As depicted in figs. 1 and 2.In Fig. 1 and Fig. 2, just indicate main peak spectrum; Table 1 is corresponding peak, each peak result table in Fig. 1, as shown in table 1, and table 2 is corresponding peak, each peak result table in Fig. 2, as shown in table 2.
Corresponding peak, each peak result table in table 1 Fig. 1
| Sequence number | Retention time (minute) | Area (microvolt second) | % area |
| 1 | 1.570 | 4881 | 0.01 |
| 2 | 1.698 | 13723 | 0.04 |
| 3 | 2.034 | 22007 | 0.06 |
| 4 | 2.220 | 70390 | 0.20 |
| 5 | 3.728 | 5852 | 0.02 |
| 6 | 4.071 | 8889 | 0.03 |
| 7 | 11.639 | 16964 | 0.05 |
| 8 | 14.596 | 23889 | 0.07 |
| 9 | 15.830 | 39992 | 0.12 |
| 10 | 18.466 | 614149 | 1.79 |
| 11 | 22.221 | 33201949 | 96.57 |
| 12 | 25.084 | 160705 | 0.46 |
| 13 | 34.133 | 198092 | 0.58 |
| Sum | 34381282 | 100 |
Corresponding peak, each peak result table in table 2 Fig. 2
| Sequence number | Retention time (minute) | Area (microvolt second) | % area |
| 1 | 3.261 | 343452 | 3.67 |
| 2 | 9.732 | 535166 | 5.72 |
| 3 | 12.100 | 216468 | 2.32 |
| 4 | 17.128 | 8254790 | 88.29 |
| Sum | 9349876 | 100 |
Proton nmr spectra (
1h-NMR), hydrogen atom has magnetic, and as electromagnetic wave irradiation hydrogen nuclei, it can pass through resonance absorption electromagnetic wave energy, and transition occurs.Can be recorded to relevant signal by nuclear magnetic resonance analyser, be in the frequency difference of hydrogen atom in varying environment electromagnetic wave absorption when producing resonance, the position occurring on collection of illustrative plates is also different, utilize chemical shift, the information such as peak area and integrated value and coupling constant, and then infer its position on carbon skeleton.
The quantity at peak is exactly the quantity of the chemical environment of hydrogen, and the relative height at peak is exactly the quantity of the hydrogen atom in certain chemical environment of correspondence.The automatic integrator that uses nuclear magnetic resonance analyser to carry can carry out automatic integration to the area at each peak, and the numerical value obtaining shows with staged integrated curve height.
Mass spectrometry (Mass Spectrometry, MS) is molion and the fragmention quality of working sample in high vacuum system, to determine the method for sample relative molecular mass and molecular structure.Compound molecule is subject to stream of electrons impact after, positively charged molion and the fragmention of formation, according to the ratio m/z(mass-to-charge ratio of its quality m and electric charge z) size is arranged in order and the collection of illustrative plates that goes on record, is called mass spectrum.In qualification organic four large important means (NMR, MS, IR, UV), mass spectrometry is that the unique method that can determine molecular formula (is measured precision and reached 10
-4), ESI-MS is that the ionizer of mass spectrum the inside is ESI.
Prepared 16min vinorelbine tartrate derivative is done to proton nmr spectra and mass spectrometric detection, the detecting instrument of described proton nmr spectra is: superconduction pulse fourier transform nmr spectrometer, BrukerAVANCE AV 400, testing conditions is: solvent is CDCl3, and detected temperatures is 30 DEG C; The detecting instrument of described mass spectrometric detection is: LCQ Deca XP liquid-matter is used in conjunction instrument, and testing conditions is: mass spectrum parameter is ESI, and sheath gas velocity is 15(arb), capillary temperature is 250 DEG C, and capillary voltage is 18V, and spray voltage is+3kV.
Fig. 3 is 16min vinorelbine tartrate derivative in the embodiment of the present invention
1h-NMR collection of illustrative plates; Fig. 4 is 16min vinorelbine tartrate derivative ESI-MS collection of illustrative plates in the embodiment of the present invention; As shown in Figure 4, in ESI-MS, occur [M] peak 871.2 and [M+2] peak 873.2, and intensity is bordering on 1:1, proves this compound tool halogens Br.Use gopher, for example, after science finder checks, this compound is new compound, called after 6'-N-methyl-17-bromo vinorelbine tartrate.
Table 3 is vinorelbine tartrate derivative 16min
1h-NMR attribution data table, as shown in table 3.
Table 3 vinorelbine tartrate derivative 16min
1h-NMR attribution data table
Embodiment 4
A preparation method for vinorelbine tartrate derivative, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, described normal phase silicagel column granularity is 200～300 orders, and carries out gradient elution by chloroform-methanol system, and described chloroform-methanol system volume ratio is 100:1-1:1;
B, detect by tlc, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared by high performance liquid chromatography, mobile phase A is acetonitrile mutually, B is diethylamine-purified water mutually, described B mutually middle diethylamine-purified water volume ratio is 14:986, and the volume ratio of described A phase and B phase is 60:40, preparation 16min vinorelbine tartrate derivative.
Detect preparing the auspicious derivative in gained 16min tartrate Changchun by high performance liquid chromatography, find all peaks stack and overlapping, cannot effectively detect described 16min vinorelbine tartrate derivative.
Embodiment 5
A preparation method for vinorelbine tartrate derivative, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, described normal phase silicagel column granularity is 200～300 orders, and carries out gradient elution by chloroform-methanol system, and described chloroform-methanol system volume ratio is 100:1-1:1;
B, detect by tlc, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared by high performance liquid chromatography, mobile phase A is acetonitrile mutually, B is diethylamine-purified water mutually, described B mutually middle diethylamine-purified water volume ratio is 14:986, and the volume ratio of described A phase and B phase is 30:70, preparation 16min vinorelbine tartrate derivative.
Detect preparing the auspicious derivative in gained 16min tartrate Changchun by high performance liquid chromatography, find all peaks stack and overlapping, cannot effectively detect described 16min vinorelbine tartrate derivative.
Comprehensive described embodiment 1-5 is known, the optimum volume ratio of described A phase and described B phase is 50:50, each peak of preparing the 16min vinorelbine tartrate derivative of gained obviously shows, and makes a kind of new compound, 6'-N-methyl-17-bromo vinorelbine tartrate.
The present invention, taking vinorelbine tartrate as initiator, obtains and identifies new compound 6'-N-methyl-17-bromo vinorelbine tartrate by a series of separation and purification means, and the present invention has following beneficial effect:
1, analyzed vinorelbine tartrate related derivatives by 6'-N-methyl-17-bromo vinorelbine tartrate and produced possible condition, for the quality control such as technology controlling and process and sample retention provides foundation.
2, set up vinorelbine tartrate related derivatives high performance liquid chromatography preparation method, for the qualification of vinorelbine tartrate derivative provides strong reference.
3, according to the structure of 6'-N-methyl-17-bromo vinorelbine tartrate, for the mechanism of vinorelbine tartrate synthesis technique provides reference.
The foregoing is only preferred embodiment of the present invention, in order to limit the present invention, within the spirit and principles in the present invention not all, any amendment of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (10)
1. a preparation method for vinorelbine tartrate derivative, is characterized in that, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, and carry out gradient elution with eluent;
B, detect with thin-layer chromatography, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared at 16min and obtains 6'-N-methyl-17-bromo vinorelbine tartrate by high performance liquid chromatography.
2. the preparation method of vinorelbine tartrate derivative according to claim 1, it is characterized in that, it further comprises step c: 6'-N-methyl-17-bromo vinorelbine tartrate that in described step b, high performance liquid chromatography prepares is carried out to mass spectrum and proton nmr spectra detection.
3. the preparation method of vinorelbine tartrate derivative according to claim 1, it is characterized in that: in described step a, normal phase silicagel column granularity is 200～300 orders, in described step a, eluent is chloroform-methanol system, and the volume ratio of described chloroform-methanol system is 100:1-1:1.
4. the preparation method of vinorelbine tartrate derivative according to claim 1, it is characterized in that: in described step b, high performance liquid chromatography preparation method's mobile phase A is acetonitrile mutually, B is diethylamine-purified water mutually, described B mutually middle diethylamine-purified water volume ratio is 14:986, and described A phase and described B phase volume ratio are A:B=50:50.
5. a method of purification for vinorelbine tartrate derivative, is characterized in that, comprises the steps:
A, vinorelbine tartrate is concentrated, use purification on normal-phase silica gel column chromatography after concentrated, and carry out gradient elution with eluent;
B, detect with thin-layer chromatography, merging in described step a volume ratio in eluent is 20:1～10:1 flow point, described flow point is prepared at 16min and obtains 6'-N-methyl-17-bromo vinorelbine tartrate by high performance liquid chromatography.
6. the method for purification of vinorelbine tartrate derivative according to claim 5, it is characterized in that, it further comprises step c: 6'-N-methyl-17-bromo vinorelbine tartrate that in described step b, high performance liquid chromatography prepares is carried out to mass spectrum and proton nmr spectra detection.
7. the method for purification of vinorelbine tartrate derivative according to claim 5, it is characterized in that: in described step a, normal phase silicagel column granularity is 200～300 orders, in described step a, eluent is chloroform-methanol system, and the volume ratio of described chloroform-methanol system is 100:1-1:1.
8. the method for purification of vinorelbine tartrate derivative according to claim 5, it is characterized in that: in described step b, high performance liquid chromatography preparation method's mobile phase A is acetonitrile mutually, B is diethylamine-purified water mutually, described B mutually middle diethylamine-purified water volume ratio is 14:986, and described A phase and described B phase volume ratio are A:B=50:50.
9. a vinorelbine tartrate derivative, is characterized in that, the structural formula of described 6'-N-methyl-17-bromo vinorelbine tartrate is:
10. vinorelbine tartrate derivative according to claim 9, is characterized in that: described 6'-N-methyl-17-bromo vinorelbine tartrate is detected and drawn its structural formula by mass spectrum and proton nmr spectra.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210559799.9A CN103880866B (en) | 2012-12-19 | 2012-12-19 | A kind of vinorelbine tartrate derivant and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210559799.9A CN103880866B (en) | 2012-12-19 | 2012-12-19 | A kind of vinorelbine tartrate derivant and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103880866A true CN103880866A (en) | 2014-06-25 |
| CN103880866B CN103880866B (en) | 2016-09-28 |
Family
ID=50950029
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210559799.9A Active CN103880866B (en) | 2012-12-19 | 2012-12-19 | A kind of vinorelbine tartrate derivant and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103880866B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109206442A (en) * | 2017-06-29 | 2019-01-15 | 江苏汉邦科技有限公司 | A kind of preparation method of vinorelbine monomer |
| CN109988184A (en) * | 2017-12-29 | 2019-07-09 | 江苏豪森药业集团有限公司 | The purification process of vinorelbine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4307100A (en) * | 1978-08-24 | 1981-12-22 | Agence Nationale De Valorisation De La Recherche (Anvar) | Nor bis-indole compounds usable as medicaments |
| WO2005055943A2 (en) * | 2003-12-04 | 2005-06-23 | Amr Technology, Inc. | Vinorelbine derivatives |
| CN101508697A (en) * | 2009-03-27 | 2009-08-19 | 广州汉方现代中药研究开发有限公司 | Preparation method for vinorelbine |
-
2012
- 2012-12-19 CN CN201210559799.9A patent/CN103880866B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4307100A (en) * | 1978-08-24 | 1981-12-22 | Agence Nationale De Valorisation De La Recherche (Anvar) | Nor bis-indole compounds usable as medicaments |
| WO2005055943A2 (en) * | 2003-12-04 | 2005-06-23 | Amr Technology, Inc. | Vinorelbine derivatives |
| CN101508697A (en) * | 2009-03-27 | 2009-08-19 | 广州汉方现代中药研究开发有限公司 | Preparation method for vinorelbine |
Non-Patent Citations (3)
| Title |
|---|
| XIAOJI CAO，等: "Characterization of impurities in semi-synthetic vinorelbine bitartrate by HPLC-MS with mass spectrometric shift technique", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
| 李硕: "长春花属生物碱抗肿瘤药物的半合成研究", 《华中科技大学博士学位论文》 * |
| 金美春: "酒石酸长春瑞滨相关杂质研究", 《浙江大学硕士学位论文》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109206442A (en) * | 2017-06-29 | 2019-01-15 | 江苏汉邦科技有限公司 | A kind of preparation method of vinorelbine monomer |
| CN109988184A (en) * | 2017-12-29 | 2019-07-09 | 江苏豪森药业集团有限公司 | The purification process of vinorelbine |
| CN109988184B (en) * | 2017-12-29 | 2021-12-17 | 江苏豪森药业集团有限公司 | Purification method of vinorelbine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103880866B (en) | 2016-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | A strategy for comprehensive identification of sequential constituents using ultra-high-performance liquid chromatography coupled with linear ion trap–Orbitrap mass spectrometer, application study on chlorogenic acids in Flos Lonicerae Japonicae | |
| Sarker et al. | Hyphenated techniques and their applications in natural products analysis | |
| Patel et al. | Introduction to hyphenated techniques and their applications in pharmacy | |
| Jayaprakasha et al. | Simultaneous separation and identification of limonoids from citrus using liquid chromatography‐collision‐induced dissociation mass spectra | |
| Gomes et al. | Hybrid MS/NMR methods on the prioritization of natural products: applications in drug discovery | |
| Zhou et al. | Characterization of polyprenylated xanthones in Garcinia xipshuanbannaensis using liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry | |
| Nawwar et al. | High‐performance Liquid Chromatographic/Electrospray Ionization Mass Spectrometric Screening for Polyphenolic Compounds of Epilobium hirsutum—The Structure of the Unique Ellagitannin Epilobamide‐A | |
| CN110320302A (en) | The quickly method of measurement methotrexate (MTX) blood concentration | |
| Zhang et al. | A metabolomic strategy based on integrating headspace gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry to differentiate the five cultivars of Chrysanthemum flower | |
| CN103880866A (en) | Navelbine tartrate derivative and preparation method thereof | |
| Yang et al. | Analysis of E. rutaecarpa alkaloids constituents in vitro and in vivo by UPLC-Q-TOF-MS combined with diagnostic fragment | |
| Terajima et al. | Simple structural elucidation of ostreocin‐B, a new palytoxin congener isolated from the marine dinoflagellate Ostreopsis siamensis, using complementary positive and negative ion liquid chromatography/quadrupole time‐of‐flight mass spectrometry | |
| Qu et al. | Combining multidimensional chromatography-mass spectrometry and feature-based molecular networking methods for the systematic characterization of compounds in the supercritical fluid extract of Tripterygium wilfordii Hook F | |
| Zhang et al. | A simple and rapid UPLC-PDA method for quality control of Nardostachys jatamansi | |
| CN103880865A (en) | Vinorelbine tartrate derivative and preparation method thereof | |
| Wu et al. | Development of the fingerprint for the quality of Radix Linderae through ultra‐pressure liquid chromatography‐photodiode array detection/electrospray ionization mass spectrometry | |
| CN107589187B (en) | Extraction method and determination method of residual maleic hydrazide in tobacco | |
| Shan et al. | Rapid screening and identification of lycodine‐type alkaloids in Lycopodiaceae and Huperziaceae plants by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry | |
| Zhao et al. | Separation, determination and identification of the diastereoisomers of podophyllotoxin and its esters by high-performance liquid chromatography/tandem mass spectrometry | |
| CN107643342A (en) | The analysis method of hopanoid compound in a kind of petroleum geology sample | |
| CN106680401B (en) | The quantitative approach of parabens compound in a kind of measurement deposit | |
| Wada et al. | Stereochemistry of norditerpenoid alkaloids by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry | |
| CN102662011B (en) | Use of spermidine as anoxia preconditioning biomarker | |
| CN110272464B (en) | Compound, preparation method thereof and application thereof in preparing antitumor drugs | |
| CN107643357B (en) | Analysis method of sterane compound in petroleum geological sample |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |