CN102464703A - Method for obtaining high purity echinocandin D - Google Patents
Method for obtaining high purity echinocandin D Download PDFInfo
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- CN102464703A CN102464703A CN2010105338764A CN201010533876A CN102464703A CN 102464703 A CN102464703 A CN 102464703A CN 2010105338764 A CN2010105338764 A CN 2010105338764A CN 201010533876 A CN201010533876 A CN 201010533876A CN 102464703 A CN102464703 A CN 102464703A
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Abstract
The invention discloses a method for obtaining high purity echinocandin D. The method comprises the steps of: (1) mixing a solution containing an echinocandin D crude product with a methanol aqueous solution 1 so as to obtain a solution 1; (2) loading the solution 1 to a reversed-phase chromatography column; and (3) conducting elution with a methanol aqueous solution 2, thus obtaining the high purity echinocandin D.
Description
Technical field
The present invention relates to the purification process of compound, relate in particular to a kind of method that obtains high purity echinocandin D.
Background technology
The echinocandin compounds is that a type of the discovery seventies in 20th century has cyclic hexapeptide core and the natural ring-type lipopeptide compound of fatty acid side chain structure.Be divided into different compounds according to different substituting group and fatty acid side chains on ring six peptides.The echinocandin compounds belongs to one type of new class of antifungal, and as glucan synthase inhibitors, noncompetitive ground suppresses the synthesizing of β-(1,3)-D-VISOSE of fungal cell wall and brings into play germicidal action.Can produce a lot of similar components (USP 4024245) during the fermentation.Wherein echinocandin D has and the similar bacteriostatic activity of ECB; Therefore have exploitation and be worth (USP 4024245,495878,495652); Yet the low 20-200 of the rate ratio ECB of echinocandin D times during the fermentation, later separation is extracted difficulty, and cost is higher.
The structure of ECB and echinocandin D
| Compound | R1 | R2 | R3 |
| ECB | OH | OH | OH |
| Echinocandin D | H | H | H |
The report of the relevant separation and purification of echinocandin D seldom only comes from that (4024245) have play-by-play, its process using chloroform extraction, ether sedimentation, silica gel column chromatography method separation and purification echinocandin D in the related patent U.S. Patent No. that gift comes company.Contain impurity such as pigment (color is for yellow or faint yellow) among the echinocandin D that obtains by this method, about the about 70%-90% of purity, yield lower (40-60%), and use acetonitrile, chloroform toxic reagent in a large number, cost is high, is difficult to large-scale application.
Therefore, this area presses for the method that a kind of new acquisition high purity echinocandin D is provided.
Summary of the invention
The present invention aims to provide the preparation method of a kind of high purity echinocandin D.
In the present invention, the preparation method of a kind of high purity echinocandin D is provided, described method comprises step:
The solution and the methanol aqueous solution 1 that (1) will contain echinocandin D bullion mix, and obtain solution 1;
(2) with on the solution 1 appearance to the reversed phase chromatography post; With
(3) carry out wash-out with methanol aqueous solution 2, obtain high purity echinocandin D.
In another preference, in the said TV that contains the solution of echinocandin D bullion, wherein the content of echinocandin D bullion is 10-90w/L%; Preferably, the content of echinocandin D bullion is 70-90w/L%; More preferably, the content of echinocandin D bullion is 80-90w/L%.
In another preference, in the TV of said methanol aqueous solution 1, wherein the content of methyl alcohol is 30-65L/L%; Preferably, be 50-60L/L%.
In another preference, said reversed phase chromatography post is selected from NM-PS 100, MCI or C18.
In another preference, in the TV of said methanol aqueous solution 2, wherein the content of methyl alcohol is 60-90L/L%; Preferably, be 82-87L/L%.
In another preference, the content of methyl alcohol is than the high 20-30L/L% of content of methyl alcohol in the methanol aqueous solution 1 in the methanol aqueous solution 2.
In another preference, described step (3) is to carry out wash-out with methanol aqueous solution 2, and the elutriant evaporate to dryness of the echinocandin D that obtains is dissolved in methyl alcohol, adds less water its supersaturation post crystallization is separated out, and obtains high purity echinocandin D.
In view of the above, the invention provides the method for a kind of new acquisition high purity echinocandin D.
Description of drawings
Fig. 1 is the HPLC collection of illustrative plates of the echinocandin D that obtains of the embodiment of the invention 1 purifying.
Embodiment
The contriver is through deep research, found the method for a kind of brand-new purifying echinocandin D, this method not only technology simple, need not expensive plant and instrument; Be easy to large-scale application; And purity reaches more than 95%, and yield is high, can satisfy the needs of correlative study.Accomplished the present invention on this basis.
Particularly, the method for purifying echinocandin D provided by the invention may further comprise the steps:
The first step, the solution and the methanol aqueous solution 1 that will contain echinocandin D bullion mix, and obtain solution 1;
Second the step, with on the solution 1 appearance to the reversed phase chromatography post; With
The 3rd step, carry out wash-out with methanol aqueous solution 2, obtain high purity echinocandin D.
In the first step, the said solution that contains echinocandin D bullion, in its TV, wherein the content of echinocandin D bullion is 10-90w/L%; Preferably be 70-90w/L%; More preferably be 80-90w/L%.
In the first step, said methanol aqueous solution 1, in its TV, wherein the content of methyl alcohol is 30-65L/L%, preferred 50-60L/L%.
In second step, the filler of said reversed phase chromatography post is selected from polymkeric substance (PS, Vinylstyrene, polyacrylic ester etc.) and is the filler of matrix, more preferably is the filler of matrix for PS.The 100g reverse phase filler is separated smaller or equal to 0.5g echinocandin D.
In the 3rd step, said methanol aqueous solution 2, in its TV, wherein the content of methyl alcohol is 60-90, preferred 82-87L/L%.
In purification process of the present invention, the content of methyl alcohol is than the high 20-30L/L% of content of methyl alcohol in the methanol aqueous solution in the first step 1 in the methanol aqueous solution 2 in the 3rd step.
In purification process of the present invention, the 3rd step was: carry out wash-out with methanol aqueous solution 2, the elutriant evaporate to dryness of the echinocandin D that obtains is dissolved in methyl alcohol, the adding less water is separated out its supersaturation post crystallization, obtains high purity echinocandin D.
As used herein; " purity of echinocandin D " or " the HPLC purity of echinocandin D " can be exchanged use; All be meant under performance liquid chromatography provided by the invention (HPLC) testing conditions the per-cent of the peak area of the echinocandin D that records and the peak area sum at all peaks.
As used herein, " bullion of echinocandin D " is meant under performance liquid chromatography provided by the invention (HPLC) testing conditions, the mixture of the content of echinocandin D＜90% (w/w or w/l).Can use the existing method in this area to obtain the bullion of echinocandin D, such as but not limited to, fermented liquid or fermented liquid are through extracting the product that obtains, or other have the product of corresponding content.
As used herein; " solution that contains echinocandin D bullion " is meant the solution that contains target echinocandin D and one or more non-target compounds; The buffered soln of dissolving crude product in water or pH≤7 that can be echinocandin D obtains; Also can be the reaction solution of the echinocandin D that obtains of any process, through with the mixing solutions that contains organic solvent of the buffered soln mixing gained of water or pH≤7.Can use the reaction solution of the echinocandin D that method obtained of this area existing preparation echinocandin D, such as but not limited to, with microbial fermentation and/or, the reaction solution that obtains through the multistep chemical reaction.Such as: Journal of the American Chemical Society, 1986,108 (19), pages:6041-6045 reaches and should print 1987,109 (23), pages:7151 and Tetrahedron, 1993, Volume 49 (28), pages:6195-6222.
Report its compound method.The reaction solution of above echinocandin D only is that the reaction solution of echinocandin D of the present invention should be not limited for example.
As used herein, " reversed phase chromatography " is meant in adsorption chromatography, if on upholder, be coated with the strong alkanes of the hydrophobicity of last layer high carbon atom; Elutriant is with the strong solvent of polarity; The strong material of polarity in the then separated sample is not adsorbed, and washes at first, and obtains separating effect preferably.This chromatography and common adsorption chromatography are opposite, so be called reversed phase chromatography.At present reversed phase chromatography is commonly used has the silica filler that has different bonding phases; Like C18, C12, C8, C4, C2, CN etc.; With polymkeric substance (PS, Vinylstyrene, polyacrylic ester etc.) is the filler of matrix; Mineral filler such as graphitized carbon etc., the present invention preferably uses the filler of polymkeric substance (PS, Vinylstyrene, polyacrylic ester etc.) as matrix.This area polymkeric substance (PS, Vinylstyrene, polyacrylic ester etc.) commonly used is that the reverse phase filler of the filler of matrix includes but not limited to; PolymerC18 (YMC company); LichrospherWP300RP, the CG series of AMBERCHROM and XT series, the MCI GEL series of Mitsubishi Chemical; The resin base reverse phase filler of Hisep is received little scientific and technological polymer packing etc.
As used herein, " going up appearance " is meant that the solution with the bullion that contains echinocandin D contacts with the reversed phase chromatography post, makes the bullion of echinocandin D be adsorbed onto the process on the reversed phase chromatography post.Described contact comprises the reversed phase chromatography fixed phase stuffing directly dropped in the solution, then whip attachment; Also have the reversed phase chromatography fixed phase stuffing is packed in the chromatographic apparatus, make solution stream cross chromatography column.
Molecule " wash-out " from the reversed phase chromatography post is got off, refer to use the strong elutriant of the polarity material that polarity is strong to remove down from the reversed phase chromatography post earlier through changing.
As used herein, " elutriant " is used for target echinocandin D is eluted from solid phase.The polarity of elutriant can make target echinocandin D to elute from the reversed phase chromatography post with the different order of other material.
" purifying " echinocandin D from the compsn that contains target echinocandin D and one or more non-target compounds, refer to through from compsn (wholly or in part) remove the purity that at least a non-target compound improves echinocandin D in the compsn.
The above-mentioned characteristic that the present invention mentions, or the characteristic that embodiment mentions can arbitrary combination.All characteristics that this case specification sheets is disclosed can with any composition forms and usefulness, each characteristic that is disclosed in the specification sheets can anyly provide the alternative characteristics of identical, impartial or similar purpose to replace.Therefore removing has special instruction, the characteristic that is disclosed to be merely the general example of equalization or similar features.
Major advantage of the present invention is:
1, technology simple, need not expensive plant and instrument, operation, maintenance cost are low, are easy to popularize, and have very high commercial value.
2, the purity of the echinocandin D that obtains of purification process provided by the invention can reach the level more than 95%, and yield high (more than 98%) can satisfy the requirement of carrying out correlative study.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in the restriction scope of the present invention.The experimental technique of unreceipted actual conditions in the following example is usually according to the normal condition or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise all percentage ratio, ratio, ratio or umber by weight.
Unit in the percent weight in volume among the present invention is well-known to those skilled in the art, for example is meant the weight of solute in 100 milliliters solution.
Only if definition separately, the same meaning that employed all specialties and scientific words and one skilled in the art are familiar with in the literary composition.In addition, any with the institute similar content of putting down in writing or the equalization method and material all can be applicable in the inventive method.The usefulness that preferable implementation method described in the literary composition and material only present a demonstration.
The detection method of echinocandin D is a HPLC among the present invention, and concrete detection method is following:
Chromatographic column: ODS-C18 (250mm * 4.6mm, i.d 5 μ m).
Moving phase: methyl alcohol: acetonitrile: water (7: 2: 1).
Sample size: 20 μ L.
Flow velocity: 1.0mL/min.
Column temperature: 30 ℃.
Ultraviolet detection wavelength: 221nm.
The filler of the reversed phase chromatography post that uses in the embodiment of the invention has:
The NM-PS100 filler
Available from Nano Technology Co., Ltd.
Particle diameter: 50-100 μ m
Specific surface area: 900m
2/ g
The MCI-GEL filler
Available from Mitsubishi Chemical
Particle diameter: 75-150 μ m
Specific surface area: 520m
2/ g
The C18 filler
Available from Daiso company
Particle diameter: 40-60 μ m
Specific surface area: 200m
2/ g
Embodiment 1
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting HPLC purity is 95.5%; Yield 98%, white.See accompanying drawing 1 for details.
Embodiment 2 (methanol concentration that appearance is used on the sample is to the influence of purifying)
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 70% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 92%; Yield 98%, faint yellow.
Embodiment 3 (methanol concentration that appearance is used on the sample is to the influence of purifying)
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 50% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 95%; Yield 98%, white.
Embodiment 4 (methanol concentration that appearance is used on the sample is to the influence of purifying)
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 30% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D has on a small quantity on post and separates out; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 95%; Yield 95%, white.
Embodiment 5 (filler is to the influence of purifying)
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 60% methanol aqueous solution MCI of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 90%; Yield 98%, yellow.
Embodiment 6 (filler is to the influence of purifying)
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 60% methanol aqueous solution C18 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 92%; Yield 97%, faint yellow.
Embodiment 7 (the elutriant methanol concentration is to the influence of purifying)
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 50% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 90% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 89%; Yield 98%, yellow.
Embodiment 8 (the elutriant methanol concentration is to the influence of purifying)
(4 * 20cm) reversed-phase columns will contain 80% echinocandin D sample 0.5g and be dissolved in 50% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 80% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 95%; Yield 89%, white.
Embodiment 9
(4 * 20cm) reversed-phase columns will contain 90% echinocandin D sample 0.5g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 96.5%; Yield 98%, white.
(4 * 20cm) reversed-phase columns will contain 70% echinocandin D sample 0.5g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 95.2%; Yield 98%, white.
Embodiment 11
(4 * 20cm) reversed-phase columns will contain 40% echinocandin D sample 0.5g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 95%; Yield 98%, white.
Embodiment 12
(4 * 20cm) reversed-phase columns will contain 10% echinocandin D sample 0.5g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 94.5%; Yield 96%, white.
Embodiment 13
The NM-PS100 of dress 100g (4 * 20cm) reversed-phase columns, the fermentation broth extract 0.5g (process for extracting among the referenced patent US4024245) that will contain 2% echinocandin D is dissolved in 60% methanol aqueous solution, crosses post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 92.5%; Yield 95%, faint yellow.
Embodiment 14
The NM-PS100 of dress 100g (4 * 20cm) reversed-phase columns, the fermentation broth extract 0.5g (process for extracting among the referenced patent US4024245) that will contain 3.5% echinocandin D is dissolved in 60% methanol aqueous solution, crosses post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 93%; Yield 95%, faint yellow.
The NM-PS100 of dress 100g (4 * 20cm) reversed-phase columns, the fermentation broth extract 0.5g (process for extracting among the referenced patent US4024245) that will contain 5% echinocandin D is dissolved in 60% methanol aqueous solution, crosses post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 93%; Yield 95%, faint yellow.
Embodiment 16
(4 * 20cm) reversed-phase columns are dissolved in the echinocandin D extract 0.5g behind the silica gel column chromatography (silica gel column chromatography method among the referenced patent US4024245, the content of echinocandin D are 70%) in 60% methanol aqueous solution NM-PS100 of dress 100g; Cross post, echinocandin D is attracted on the post fully, uses 85% methanol aqueous solution wash-out pillar; Distribute and collect the higher part of elutriant moderate purity; Detecting purity is 95.2%, yield 98%, white.
Embodiment 17
(4 * 20cm) reversed-phase columns are dissolved in the echinocandin D extract 0.5g behind the silica gel column chromatography (silica gel column chromatography method among the referenced patent US4024245, the content of echinocandin D are 80%) in 60% methanol aqueous solution NM-PS100 of dress 100g; Cross post, echinocandin D is attracted on the post fully, uses 85% methanol aqueous solution wash-out pillar; Distribute and collect the higher part of elutriant moderate purity; Detecting purity is 95.5%, yield 98%, white.
Embodiment 18
(4 * 20cm) reversed-phase columns are dissolved in the echinocandin D extract 0.5g behind the silica gel column chromatography (silica gel column chromatography method among the referenced patent US4024245, the content of echinocandin D are 90%) in 60% methanol aqueous solution NM-PS100 of dress 100g; Cross post, echinocandin D is attracted on the post fully, uses 85% methanol aqueous solution wash-out pillar; Distribute and collect the higher part of elutriant moderate purity; Detecting purity is 96.5%, yield 98%, white.
Embodiment 19
(4 * 20cm) reversed-phase columns are dissolved in the echinocandin D extract 0.5g behind the silica gel column chromatography (silica gel column chromatography method among the referenced patent US4024245, the content of echinocandin D are 40%) in 60% methanol aqueous solution NM-PS100 of dress 100g; Cross post, echinocandin D is attracted on the post fully, uses 85% methanol aqueous solution wash-out pillar; Distribute and collect the higher part of elutriant moderate purity; Detecting purity is 95%, yield 98%, white.
Embodiment 20
(4 * 20cm) reversed-phase columns are dissolved in the echinocandin D extract 0.5g behind the silica gel column chromatography (silica gel column chromatography method among the referenced patent US4024245, the content of echinocandin D are 10%) in 60% methanol aqueous solution NM-PS100 of dress 100g; Cross post, echinocandin D is attracted on the post fully, uses 85% methanol aqueous solution wash-out pillar; Distribute and collect the higher part of elutriant moderate purity; Detecting purity is 94%, yield 98%, white.
Embodiment 21
(4 * 20cm) reversed-phase columns will contain 90% echinocandin D sample 0.6g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 95%; Yield 98%, white.
Embodiment 22
(4 * 20cm) reversed-phase columns will contain 90% echinocandin D sample 0.4g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 96.5%; Yield 98%, white.
Embodiment 23
(4 * 20cm) reversed-phase columns will contain 90% echinocandin D sample 0.3g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 96.8%; Yield 98%, white.
Embodiment 24
(4 * 20cm) reversed-phase columns will contain 90% echinocandin D sample 0.7g and be dissolved in 60% methanol aqueous solution NM-PS100 of dress 100g, cross post; Echinocandin D is attracted on the post fully; Use 85% methanol aqueous solution wash-out pillar, distribute and collect the higher part of elutriant moderate purity, detecting purity is 94%; Yield 98%, white.
Embodiment 25 (crystallization)
The NM-PS100 post is separated the 96.5% echinocandin D elutriant evaporate to dryness that obtains be dissolved in methyl alcohol, add less water its supersaturation post crystallization is separated out, detecting purity is 97%.White.
Embodiment 26
Be dissolved in methyl alcohol with separating the 90% echinocandin D elutriant evaporate to dryness that obtains, add less water its supersaturation post crystallization is separated out, detecting purity is 93%.Faint yellow.
The above is merely preferred embodiment of the present invention; Be not in order to limit essence technology contents scope of the present invention; Essence technology contents of the present invention is broadly to be defined in the claim scope of application, and if any technological entity or method that other people accomplish are defined identical with the claim scope of application; Also or a kind of change of equivalence, all will be regarded as and be covered by among this claim scope.
Claims (9)
1. the preparation method of a high purity echinocandin D is characterized in that, described method comprises step:
The solution and the methanol aqueous solution 1 that (1) will contain echinocandin D bullion mix, and obtain solution 1;
(2) with on the solution 1 appearance to the reversed phase chromatography post; With
(3) carry out wash-out with methanol aqueous solution 2, obtain high purity echinocandin D.
2. preparation method as claimed in claim 1 is characterized in that, in the said TV that contains the solution of echinocandin D bullion, wherein the content of echinocandin D bullion is 10-90w/L%.
3. preparation method as claimed in claim 2 is characterized in that, the content of echinocandin D bullion is 70-90w/L%.
4. preparation method as claimed in claim 3 is characterized in that, the content of echinocandin D bullion is 80-90w/L%.
5. preparation method as claimed in claim 1 is characterized in that, in the TV of said methanol aqueous solution 1, wherein the content of methyl alcohol is 30-65L/L%, preferred 50-60L/L%.
6. preparation method as claimed in claim 1 is characterized in that, said reversed phase chromatography post is selected from NM-PS100, MCI or C18.
7. preparation method as claimed in claim 1 is characterized in that, in the TV of said methanol aqueous solution 2, wherein the content of methyl alcohol is 60-90L/L%, preferred 82-87L/L%.
8. preparation method as claimed in claim 1 is characterized in that, the content of methyl alcohol is than the high 20-30L/L% of content of methyl alcohol in the methanol aqueous solution 1 in the methanol aqueous solution 2.
9. like the arbitrary described preparation method of claim 1-8; It is characterized in that described step (3) is to carry out wash-out with methanol aqueous solution 2, the elutriant evaporate to dryness of the echinocandin D that obtains is dissolved in methyl alcohol; Add less water its supersaturation post crystallization is separated out, obtain high purity echinocandin D.
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| CN201010533876.4A CN102464703B (en) | 2010-11-05 | 2010-11-05 | Method for obtaining high purity echinocandin D |
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| CN201010533876.4A CN102464703B (en) | 2010-11-05 | 2010-11-05 | Method for obtaining high purity echinocandin D |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104447961A (en) * | 2013-09-13 | 2015-03-25 | 浙江震元制药有限公司 | Method for extracting echinocandin B mother nucleus |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4024245A (en) * | 1975-10-02 | 1977-05-17 | Eli Lilly And Company | Antibiotic A-30912 and process for production thereof |
| GB2065136A (en) * | 1979-12-13 | 1981-06-24 | Lilly Co Eli | Derivatives of cyclic peptide nuclei |
-
2010
- 2010-11-05 CN CN201010533876.4A patent/CN102464703B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4024245A (en) * | 1975-10-02 | 1977-05-17 | Eli Lilly And Company | Antibiotic A-30912 and process for production thereof |
| GB2065136A (en) * | 1979-12-13 | 1981-06-24 | Lilly Co Eli | Derivatives of cyclic peptide nuclei |
Non-Patent Citations (4)
| Title |
|---|
| 《J. Am. Chem. Soc.》 19871231 David A. Evans, et al., Synthesis of the Cyclic Hexapeptide Echinocandin D. New Approaches to the Asymmetric Synthesis of beta-Hydroxy alpha-Amino Acids 第7151-7157页 第109卷, 第23期 * |
| DAVID A. EVANS, ET AL.,: "Synthesis of the Cyclic Hexapeptide Echinocandin D. New Approaches to the Asymmetric Synthesis of β-Hydroxy α-Amino Acids", 《J. AM. CHEM. SOC.》 * |
| DAVID J. ROUSH, ET AL.,: "Preparative high-performance liquid chromatography of echinocandins", 《JOURNAL OF CHROMATOGRAPHY A》 * |
| NATSUKO KUROKAWA, ET AL.,: "Synthetic Studies on Antifungal Cyclic Peptides, Echinocandins. Stereoselective Total Synthesis of Echinocandin D via a Novel Peptide Coupling", 《TETRAHEDRON》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104447961A (en) * | 2013-09-13 | 2015-03-25 | 浙江震元制药有限公司 | Method for extracting echinocandin B mother nucleus |
| CN104447961B (en) * | 2013-09-13 | 2018-05-15 | 浙江震元制药有限公司 | The extracting method of echinocandin B parent nucleus |
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| Publication number | Publication date |
|---|---|
| CN102464703B (en) | 2014-07-09 |
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