CN113004225A - Separation and purification method of epoxidized acetyl sugar - Google Patents
Separation and purification method of epoxidized acetyl sugar Download PDFInfo
- Publication number
- CN113004225A CN113004225A CN202110244483.XA CN202110244483A CN113004225A CN 113004225 A CN113004225 A CN 113004225A CN 202110244483 A CN202110244483 A CN 202110244483A CN 113004225 A CN113004225 A CN 113004225A
- Authority
- CN
- China
- Prior art keywords
- ethyl acetate
- developing solvent
- acetyl sugar
- component
- eluting
- 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.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/32—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/36—Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epoxy Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention provides a separation and purification method of epoxy acetyl sugar, which comprises the steps of firstly oxidizing full-acetylation jinggangase enamine by using a peroxide agent to obtain a crude epoxy acetyl sugar, then dissolving the crude epoxy acetyl sugar in different solvents, and eluting and separating the crude epoxy acetyl sugar by using a silica gel column to obtain each isolate; the method is beneficial to the development of voglibose consistency evaluation work through the research on the intermediate of the raw material of voglibose.
Description
Technical Field
The invention belongs to the technical field of drug synthesis, and particularly relates to a separation and purification method of an intermediate epoxidation acetyl sugar of voglibose.
Background
Voglibose was first developed by the company Takeda, japan in 1994 under the name Basen for the first time and korea in 1998, and is used for the treatment of postprandial blood glucose elevation in diabetes. The product has similar action to acarbose, is a glucosidase inhibitor, and can inhibit hydrolysis of disaccharide and delay sugar absorption. The main domestic producer is Tianjin Wutian.
When the company carries out consistency evaluation work of voglibose, the company needs to research intermediates related in the industry, the voglibose raw material is purchased outside the company, so that no intermediate of epoxidized acetyl sugar exists, the voglibose impurity spectrum is researched, so that the research on the epoxidized acetyl sugar intermediate is needed, and the content of the epoxidized acetyl sugar intermediate in a factory purchasing voglibose outside the company is low, so that the research requirement cannot be met, therefore, the invention uses a new method for purification, and successfully carries out the methodology research.
Disclosure of Invention
The invention provides a separation and purification method of epoxy acetyl sugar, which comprises the steps of firstly using full acetylation jinggangase enamine to obtain a crude epoxy acetyl sugar product under the oxidation of a peroxide agent, and then carrying out the following steps:
(1) dissolving the crude epoxy acetyl sugar in deuterated chloroform for hydrogen spectroscopy to obtain a fingerprint peak of the crude epoxy acetyl sugar;
(2) dissolving the crude epoxy acetyl sugar in a solvent, mixing the sample with silica gel, fully drying to ensure that the crude epoxy acetyl sugar is fully adsorbed on the silica gel, and eluting 5 retention volumes by using a developing solvent to obtain a component 1;
(3) increasing polarity of the developing solvent, eluting for 5 retention volumes, and eluting the first color band (yellow) to obtain a component 2;
(4) then increasing the polarity of the developing solvent, eluting for 3 retention volumes, and eluting the first color band (yellow) to obtain a component 3;
and (3) performing nuclear magnetic characterization on the components 1, 2 and 3 respectively, and comparing the nuclear magnetic characterization with fingerprint peaks, wherein a little product exists in the component 3.
(5) And (3) continuing increasing the polarity of the developing agent, eluting 5 retention volumes, eluting a second color band (yellow) to obtain a component 4, carrying out nuclear magnetic characterization on the component 4, comparing with a fingerprint peak, and obtaining a target product which is mainly in the component 4 and has the purity of 30-80%.
(6) And (3) loading the component 4 to an ODS column, and flushing the column by using a prepared 1:1 methanol aqueous solution system to obtain a target product.
The separation and purification method of the epoxidized acetyl sugar comprises the following steps:
the solvent in the step (2) is one of dichloromethane, ethyl acetate and methanol; the developing solvent is ethyl acetate: 1: 3-8 of petroleum ether;
the developing solvent in the step (3) is ethyl acetate: 1: 1-3 of petroleum ether;
the developing solvent in the step (4) is dichloromethane. One of ethyl acetate and methanol;
the developing solvent in the step (5) is one of dichloromethane, methanol and ethyl acetate.
The separation and purification method of the epoxidized acetyl sugar comprises the following steps:
the solvent in the step (2) is ethyl acetate; the developing solvent is ethyl acetate: petroleum ether is 1: 5;
the developing solvent in the step (3) is ethyl acetate: petroleum ether is 1: 2.
The developing solvent in the step (4) is ethyl acetate;
the developing solvent in the step (5) is methanol.
Drawings
The attached figure 1 is: nuclear magnetic hydrogen spectrum;
FIG. 2 is a drawing: nuclear magnetic carbon spectrum spectrogram;
FIG. 3 is a schematic diagram of: COSY spectrum;
FIG. 4 is a drawing of: HMBC spectrogram;
FIG. 5 is a schematic representation of: HSQC spectrogram;
FIG. 6 is a schematic representation of: noesy spectrum;
FIG. 7 is a schematic representation of: high resolution mass spectrometry spectrum.
Detailed Description
The following examples are intended to further illustrate the invention, but not to limit it.
Example 1
And dissolving 10mg of crude epoxy acetyl sugar in deuterated chloroform for hydrogen spectroscopy to obtain a crude fingerprint peak.
Dissolving 1g of crude epoxy acetyl sugar in dichloromethane, mixing silica gel, fully drying to ensure that the crude epoxy acetyl sugar is fully adsorbed on the silica gel, and mixing the crude epoxy acetyl sugar with ethyl acetate: eluting 5 retention volumes with petroleum ether at a ratio of 1:3 to obtain crude product 1;
increasing the polarity to ethyl acetate: petroleum ether 1:1, elute 5 retention volumes, elute the first color band (yellow) to give fraction 2;
increasing the polarity to pure dichloromethane eluted 3 retention volumes to give fraction 3.
And respectively carrying out nuclear magnetic characterization on the components 1, 2 and 3, comparing with fingerprint peaks, and continuously having no product in the three components.
Increasing the polarity until pure dichloromethane elutes 5 retention volumes, eluting the second color band (yellow) to obtain component 4, and comparing the nuclear magnetic representation of component 4 with the fingerprint peak, the purity of the target product in component 4 is about 30%.
The fraction 4 was applied to an ODS column, and the column was washed with a 50% methanol-water system to obtain 0.25g of the aimed product.
Example 2
And dissolving 10mg of crude epoxy acetyl sugar in deuterated chloroform for hydrogen spectroscopy to obtain a crude fingerprint peak.
Dissolving 1g of crude epoxy acetyl sugar in ethyl acetate, mixing the sample with silica gel, and fully drying to ensure that the crude product is fully adsorbed on the silica gel, wherein the weight ratio of ethyl acetate: eluting 5 retention volumes with petroleum ether at a ratio of 1:5 to obtain crude product 1;
increasing the polarity to ethyl acetate: petroleum ether 1:2, elute 5 retention volumes, elute the first color band (yellow) to give fraction 2;
increase polarity to elution with pure ethyl acetate 3 retention volumes to give fraction 3.
The nuclear magnetism of the components 1, 2 and 3 is respectively characterized, and compared with fingerprint peaks, the three components have fewer products.
Increasing the polarity until 5 retention volumes are eluted by pure methanol, eluting a second color band (yellow) to obtain a component 4, carrying out nuclear magnetic characterization on the component 4, comparing with fingerprint peaks, and obtaining a target product which is mainly in the component 4 and has the purity of about 80%.
The fraction 4 was applied to an ODS column, and the column was washed with a 50% methanol-water system to obtain 0.78g of the aimed product. And carrying out structure confirmation, wherein the structure confirmation spectrogram is shown in figures 1-7.
Example 3
And dissolving 10mg of crude epoxy acetyl sugar in deuterated chloroform for hydrogen spectroscopy to obtain a crude fingerprint peak.
Dissolving 1g of crude epoxy acetyl sugar in methanol, mixing silica gel, fully drying to ensure that the crude epoxy acetyl sugar is fully adsorbed on the silica gel, and mixing the crude epoxy acetyl sugar with ethyl acetate: eluting 5 retention volumes with petroleum ether at a ratio of 1:10 to obtain crude 1;
increasing the polarity to ethyl acetate: petroleum ether 1:3, elute 5 retention volumes, elute the first color band (yellow) to give fraction 2;
increase polarity to 3 retention volumes eluted with pure methanol to give fraction 3.
And the components 1, 2 and 3 are respectively subjected to nuclear magnetic characterization, and compared with fingerprint peaks, the three components have fewer target products.
Eluting 5 retention volumes with pure ethyl acetate, eluting the second color band (yellow) to obtain component 4, and comparing the nuclear magnetic characterization of component 4 with fingerprint peaks, the purity of the target product is about 50%.
The fraction 4 was applied to an ODS column, and the column was washed with a 50% methanol-water system to obtain 0.44g of the aimed product.
Claims (3)
1. The separation and purification method of epoxy acetyl sugar comprises the steps of firstly oxidizing full acetylation jinggangase enamine by using a peroxide to obtain a crude epoxy acetyl sugar product, and is characterized by comprising the following steps:
(1) dissolving the crude epoxy acetyl sugar in deuterated chloroform for hydrogen spectroscopy to obtain a fingerprint peak of the crude epoxy acetyl sugar;
(2) dissolving the crude epoxy acetyl sugar in a solvent, mixing the sample with silica gel, fully drying to ensure that the crude epoxy acetyl sugar is fully adsorbed on the silica gel, and eluting 5 retention volumes by using a developing solvent to obtain a component 1;
(3) increasing polarity of the developing solvent, eluting for 5 retention volumes, and eluting the first color band (yellow) to obtain a component 2;
(4) then increasing the polarity of the developing solvent, eluting for 3 retention volumes, and eluting the first color band (yellow) to obtain a component 3;
respectively performing nuclear magnetic characterization on the components 1, 2 and 3, and comparing the nuclear magnetic characterization with fingerprint peaks, wherein a little product exists in the component 3;
(5) continuing to increase the polarity of the developing agent, eluting 5 retention volumes, eluting a second color band (yellow) to obtain a component 4, carrying out nuclear magnetic characterization on the component 4, comparing the nuclear magnetic characterization with a fingerprint peak, and obtaining a target product which is mainly in the component 4 and has the purity of 30-80%;
(6) and (3) loading the component 4 to an ODS column, and flushing the column by using a prepared 1:1 methanol aqueous solution system to obtain a target product.
2. The method for separating and purifying an epoxidized acetyl sugar according to claim 1, wherein the method comprises the steps of:
the solvent in the step (2) is one of dichloromethane, ethyl acetate and methanol; the developing solvent is ethyl acetate: 1: 3-8 of petroleum ether;
the developing solvent in the step (3) is ethyl acetate: 1: 1-3 of petroleum ether;
the developing solvent in the step (4) is one of dichloromethane, ethyl acetate and methanol;
the developing solvent in the step (5) is one of dichloromethane, methanol and ethyl acetate.
3. The method for separating and purifying an intermediate of an epoxidized acetyl sugar according to claim 1 or 2, wherein the method comprises the steps of:
the solvent in the step (2) is ethyl acetate; the developing solvent is ethyl acetate: petroleum ether is 1: 5;
the developing solvent in the step (3) is ethyl acetate: petroleum ether is 1: 2;
the developing solvent in the step (4) is ethyl acetate;
the developing solvent in the step (5) is methanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110244483.XA CN113004225A (en) | 2021-03-05 | 2021-03-05 | Separation and purification method of epoxidized acetyl sugar |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110244483.XA CN113004225A (en) | 2021-03-05 | 2021-03-05 | Separation and purification method of epoxidized acetyl sugar |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113004225A true CN113004225A (en) | 2021-06-22 |
Family
ID=76406572
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110244483.XA Pending CN113004225A (en) | 2021-03-05 | 2021-03-05 | Separation and purification method of epoxidized acetyl sugar |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113004225A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145650A (en) * | 2013-03-15 | 2013-06-12 | 浙江医药股份有限公司新昌制药厂 | Preparation method of (I)-effective mildew enamine pentaacetate epoxide |
-
2021
- 2021-03-05 CN CN202110244483.XA patent/CN113004225A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145650A (en) * | 2013-03-15 | 2013-06-12 | 浙江医药股份有限公司新昌制药厂 | Preparation method of (I)-effective mildew enamine pentaacetate epoxide |
Non-Patent Citations (2)
| Title |
|---|
| OGAWA, S ET AL: "Synthesis of some valienamine epoxides：on the structure of the alphaamylase inhibitor NS-504", 《CARBOHYDRATE RESEARCH》 * |
| 常景岭等: "《天然生物活性物质及其制备技术》", 31 August 2007, 河南科学技术出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mandal et al. | Steroidal saponins from the fruits of Asparagus racemosus | |
| López-López et al. | New protocol for the isolation of nitrocellulose from gunpowders: Utility in their identification | |
| Chen et al. | Diosgenin-bearing, molluscicidal saponins from Allium vineale: an NMR approach for the structural assignment of oligosaccharide units | |
| Zhang et al. | Biotransformation of bufadienolides by cell suspension cultures of Saussurea involucrata | |
| CN109761994A (en) | Carbon drop class guainane type Sesquiterpene lactones compound and preparation method thereof | |
| VANDE | FROM WITHANIA SOMNIFERA | |
| Ansari et al. | Structural studies on a saponin isolated from Nigella sativa | |
| Mu et al. | Cytotoxic triterpenoid saponins from Ardisia gigantifolia | |
| Shimizu et al. | Sesquiterpene glycosides and saponins from Cynara cardunculus L. | |
| CN107955055B (en) | Method for preparing 20-alkene 25-hydroxy ginseng rare saponin and aglycone under catalysis of metal ions | |
| Zhao et al. | Triterpenoid saponins from the roots of Clematis argentilucida and their cytotoxic activity | |
| CN113004225A (en) | Separation and purification method of epoxidized acetyl sugar | |
| Zhang et al. | A new triterpenoid saponin from the roots of Ardisia crenata | |
| Wu et al. | Rapid preparative isolation of a new phenylpropanoid glycoside and four minor compounds from S parganium stoloniferum using high‐speed counter‐current chromatography as a fractionation tool | |
| Zolfaghari et al. | Vavilosides A1/A2–B1/B2, new furostane glycosides from the bulbs of Allium vavilovii with cytotoxic activity | |
| Murakami et al. | Total synthesis of agosterol A: An MDR‐modulator from a marine sponge | |
| CN106831927B (en) | A kind of synthetic method of Astragaloside IV | |
| Zhao et al. | Three new 18, 19-seco-ursane glycosides from Elsholtzia bodinieri | |
| CN110790777B (en) | Vincristine compound impurity and preparation method and application thereof | |
| Zhong-Xiang et al. | A new triterpenoid glycoside from the roots of Ilex asprella | |
| Kimura et al. | Constituents of convallaria. IV. Isolation of convallasaponin-A,-B, and-C | |
| Yu et al. | Two new steroidal saponins from the fresh leaves of Agave sisalana | |
| Mostad et al. | Separation and characterization of oleanene-type pentacyclic triterpenes from Gypsophila arrostii by liquid chromatography—mass spectrometry | |
| West et al. | Three new polyhydroxylated sterols with the 5. beta.-configuration from the sponge Dysidea etheria | |
| Ansari et al. | Isolation and characterization of a saponin from Fagonia indica |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210622 |
|
| RJ01 | Rejection of invention patent application after publication |