CN105457613A - Preparation method of bonded area selectively modified polysaccharide derivative chiral stationary phase - Google Patents
Preparation method of bonded area selectively modified polysaccharide derivative chiral stationary phase Download PDFInfo
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- CN105457613A CN105457613A CN201510124869.1A CN201510124869A CN105457613A CN 105457613 A CN105457613 A CN 105457613A CN 201510124869 A CN201510124869 A CN 201510124869A CN 105457613 A CN105457613 A CN 105457613A
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Abstract
The invention relates to a preparation method of a bonded area selectively modified polysaccharide derivative chiral stationary phase. The method comprises the following steps: coating silica gel with a cellulose or starch derivative with a 2,3-subtituted and 6-unsubstituted glucose unit, suspending the obtained silica gel in a dry organic solvent, sequentially adding a catalyst and a silanization reagent (containing an epoxy group and a trialkyloxy silicon group) to make the epoxy group in the silanization reagent react with a 6-hydroxy group in the glucose unit, to introduce the trialkyloxy silicon group to the 6-position and carry out an intermolecular condensation polymerization reaction, deriving the 6-hydroxy group, washing the obtained material to remove a non-bonded derivative to prepare the bonded area selectively modified polysaccharide derivative chiral stationary phase. The method allowing the polysaccharide derivative to be bonded to the 6-position of the glucose unit has the advantages of no influences on the structure of the derivative, mild reactions, and realization of preparation of corresponding bonded area selectively modified polysaccharide derivative chiral stationary phases by selecting different derivatization reagents as needed.
Description
Technical field
The present invention relates to a kind of preparation method of bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase.Specifically by glucose unit 2-, 3-position is replaced by corresponding substituting group and the unsubstituted cellulose in 6-position or starch derivatives are coated on silica gel, then the silica gel being coated with derivative is suspended in dry organic solvent, add catalyst and bifunctional reagent's (containing epoxide group and silica-based group of tri-alkoxy) successively, epoxide group in bifunctional reagent and glucose unit 6-position hydroxyl are reacted, introduce the silica-based group of tri-alkoxy in 6-position and polycondensation reaction occurs, finally derive 6-position hydroxyl with corresponding reagent and prepare bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase.
Background technology
Current polysaccharide derivatives chiral stationary phase is most widely used in liquid chromatogram resolution chipal compounds.Usually this analog derivative evenly replaces, and namely glucose unit 2,3,6-position has identical substituting group.Research finds regioselectivity modified polysaccharide analog derivative (glucose unit 2,3-position has different substituting groups or 2-from 6-position, 3-, 6-position is different substituting groups) demonstrate specific chiral recognition, some chipal compounds obtain and are better separated [document 1.Kaida, Y. than on corresponding even substituted polysaccharide derivative; Okamoto, Y.Bull.Chem.Soc.Jpn., 1993,66,2225. document 2.Chassaing, C.; Thienpont, A.;
g.J.Chromatogr.A, 1996,738,157. document 3.Felix, G.J.Chromatogr.A, 2001,906,171. document 4.Kondo, S.; Yamamoto, C.; Kamigaito, M.; Okamoto, Y.Chem.Lett., 2008,37,558.].Current regioselectivity modified polysaccharide analog derivative chiral stationary phase is mostly coating-type chiral stationary phase; Derivative is coated in silica gel isochromatic spectrum matrix and obtains by this type of Stationary liquid.For coating-type chiral stationary phase, because of between derivative and matrix without any chemical bond, therefore its mobile phase range of choice is limited, and those can dissolve or the organic solvent of swelling polysaccharide derivates can not be used as Mobile Phase Additives.In order to improve the solvent tolerance of coating-type regioselectivity modified polysaccharide analog derivative chiral stationary phase, [document 5.Shen, the J. such as Shen; Ikai, T.; Shen, X.; Okamoto, Y.Chem.Lett., 2010,39,442.] prepare bonding type regioselectivity Modified Starch derivative chiral stationary phase.
Summary of the invention
The object of the invention is to develop a kind of new method preparing bonding type regioselectivity modified polysaccharide analog derivative, prepare bonding type regioselectivity modified polysaccharide analog derivative chiral material by the intermolecular polycondensation reaction between the silica-based group of tri-alkoxy introduced in glucose unit 6-position.
For achieving the above object, the technical solution used in the present invention is:
The preparation of bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase: by glucose unit 2-, 3-position is replaced by corresponding substituting group and the unsubstituted cellulose in 6-position or starch derivatives are coated on silica gel, then the silica gel being coated with derivative is suspended in dry organic solvent, add catalyst and bifunctional reagent's (containing epoxide group and silica-based group of tri-alkoxy) successively, epoxide group in bifunctional reagent and glucose unit 6-position hydroxyl are reacted and introduces the intermolecular polycondensation reaction of the concurrent life of the silica-based group of tri-alkoxy in 6-position, finally derive 6-position hydroxyl with corresponding reagent, and washing removes the derivative of non-bonding, prepare bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase.
Its detailed process is as follows:
1) by 0.10-0.40g glucose unit 2-, 3-position is replaced by corresponding substituting group and the unsubstituted cellulose in 6-position or starch derivatives are dissolved in the neat solvent of 5-20ml oxolane, acetone, chloroform, pyridine, DMA etc. or the mixed liquor of above-mentioned solvent;
2) said derivative solution is coated on 1.0g silica gel;
3) by step 2) resulting materials dry 2-8 hour at 60-100 DEG C in baking oven;
4) by step 3) resulting materials introduce be equipped with in the airtight container of nitrogen protection device, and add the organic solvent of 3-10ml drying, magnetic agitation makes silica gel fully suspend, then at 10-40 DEG C, catalyst and bifunctional reagent is added successively, and 2-12 hour is reacted at 50-100 DEG C, add the pyridine of 3-10ml drying, 0.1-1.0ml isocyanates or chlorobenzoyl chloride after reaction terminates and in 70-100 DEG C of reaction 12-24 hour, obtain bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase;
5) fully rinse above-mentioned material with oxolane and/or pyridine and/or DMA and/or dimethyl sulfoxide (DMSO), remove the polysaccharide derivates of non-bonding.
The preparation process of bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase of the present invention is schematically as follows:
Wherein, for bonding type regioselectivity modified cellulose derivative chiral stationary phase, substituent R
1=R
2≠ R
3; For bonding type regioselectivity Modified Starch derivative chiral stationary phase, substituent R
1=R
2≠ R
3or R
1≠ R
2≠ R
3, the structure of substituent R 1, R2, R3 is as follows:
Described step 4) in organic solvent be dry toluene or benzene; Catalyst is boron trifluoride complex, as boron trifluoride etherate or boron trifluoride tetrahydrofuran complex compound; Bifunctional reagent is 3-glycidol ether propyl trimethoxy silicane or 3-glycidol ether propyl-triethoxysilicane; The addition sequence of catalyst, bifunctional reagent is for first then add catalyst adds bifunctional reagent; The temperature that catalyst and bifunctional reagent add fashionable reaction solution is 10-40 DEG C; After catalyst, bifunctional reagent finish, at 50-100 DEG C of reaction 2-12 hour; The addition of bifunctional reagent is the 30%-100% (mol ratio) of glucose unit amount, and the addition of catalyst is the 5%-50% (mol ratio) of silicon difunctional dosage.
The bifunctional reagent added in reaction system is the bifunctional reagent containing epoxide group and the silica-based group of tri-alkoxy, its objective is that epoxide group and polysaccharide derivates 6-position hydroxyl react under the effect of catalyst boron trifluoride, introduce the silica-based group of tri-alkoxy in glucose unit 6-position; Tri-alkoxy is silica-based there is intermolecular polycondensation reaction in acid condition, is bonded on silica gel by regioselectivity modified polysaccharide analog derivative.
The present invention has developed a kind of new method preparing bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase.The method has the following advantages: 1, the bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase of preparation has good solvent tolerance, and the non-serviceable organic solvent of the coating-type such as oxolane, chloroform Polysaccharides Type Chiral Stationary Phases can be used to do Mobile Phase Additives; 2, only introduce binding groups in the 6-position of regioselectivity modified polysaccharide analog derivative, little on derivant structure impact, the bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase of preparation has higher chiral recognition; 3, can be used for preparing multiple bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase, reaction condition is close, has good versatility; 4, reaction condition is gentle, is easy to control, and reappearance is better.
Detailed description of the invention
Embodiment 1
1, get 0.19g2-benzoic ether-3-(3,5-dimethylphenylcarbamate)-6-hydroxyl starch, add 3ml oxolane and 3ml pyridine, vibration makes it dissolve;
2, gained solution in 1 is coated on 1.0g silica gel, by methanol wash 4 times, each 40ml; By above-mentioned material in 80 DEG C of baking ovens dry 4 hours;
3, resulting materials 0.75g in 2 is proceeded to be equipped with in two neck round-bottomed flasks of nitrogen protection device, add 5ml dry toluene, magnetic agitation makes silica gel fully suspend, then under room temperature, add boron trifluoride etherate 2 μ l, 3-glycidol ether propyl trimethoxy silicane 34 μ l successively, be warming up to 85 DEG C and at this temperature magnetic agitation react 12 hours; In above-mentioned solution, add 3ml dry pyridine, 0.7ml3,5-dichlorophenyl isocyanate and at 85 DEG C stirring reaction 12 hours;
4, resulting materials oxolane in 3 is fully washed, remove the derivative of non-bonding, obtain bonding type starch 2-benzoic ether-3-(3,5-dimethyl benzene carbamate)-6-(3,5-dichlorophenyl carbamate) chiral stationary phase.
Embodiment 2
1, get 0.20g2-benzoic ether-3-((S)-1-phenyl ethyl carbamate)-6-hydroxyl starch, add 5ml pyridine, vibration makes it dissolve;
2, gained solution in 1 is coated on 1.0g silica gel, by methanol wash 4 times, each 40ml; By above-mentioned material in 80 DEG C of baking ovens dry 4 hours;
3, resulting materials 0.75g in 2 is proceeded to be equipped with in two neck round-bottomed flasks of nitrogen protection device, add 5ml dry toluene, magnetic agitation makes silica gel fully suspend, then under room temperature, add boron trifluoride etherate 2.5 μ l, 3-glycidol ether propyl trimethoxy silicane 40 μ l successively, be warming up to 85 DEG C and at this temperature magnetic agitation react 12 hours; In above-mentioned solution, add 3ml dry pyridine, 0.6ml5-chloro-2-methyl phenyl isocyanate and at 85 DEG C stirring reaction 12 hours;
4) resulting materials oxolane in 3 is fully washed, remove the derivative of non-bonding, obtain bonding type starch 2-benzoic ether-3-((S)-1-phenyl ethyl carbamate)-6-(5-chloro-2-methyl carbanilate) chiral stationary phase.
Embodiment 3
1, get 0.21g2-benzoic ether-3-(3,5-dichlorophenyl carbamate)-6-hydroxyl starch, add 5ml pyridine, vibration makes it dissolve;
2, gained solution in 1 is coated on 1.0g silica gel, by methanol wash 4 times, each 40ml; By above-mentioned material in 80 DEG C of baking ovens dry 4 hours;
3, resulting materials 0.75g in 2 is proceeded to be equipped with in two neck round-bottomed flasks of nitrogen protection device, add 5ml dry toluene, magnetic agitation makes silica gel fully suspend, then add successively under room temperature, boron trifluoride etherate 3 μ l, 3-glycidol ether propyl trimethoxy silicane 48 μ l, be warming up to 85 DEG C and at this temperature magnetic agitation react 12 hours; In above-mentioned solution, add 3ml dry pyridine, 1.0ml3,5-dimethylphenyl isocyanate and at 85 DEG C stirring reaction 12 hours;
4, resulting materials oxolane in 3 is fully washed, remove the derivative of non-bonding, obtain bonding type starch 2-benzoic ether-3-(3,5-dichlorophenyl formic acid esters)-6-(3,5-dimethylphenylcarbamate) chiral stationary phase.
Embodiment 4
1, get 0.20g2,3-bis-(3,5-dimethylphenylcarbamate)-6-hydroxylated cellulose, adds 5ml pyridine, and vibration makes it dissolve;
2, gained solution in 1 is coated on 1.0g silica gel, by methanol wash 4 times, each 40ml; By above-mentioned material in 80 DEG C of baking ovens dry 4 hours;
3, resulting materials 0.75g in 2 is proceeded to be equipped with in two neck round-bottomed flasks of nitrogen protection device, add 5ml dry toluene, magnetic agitation makes silica gel fully suspend, then under room temperature, add boron trifluoride etherate 3.5 μ l, 3-glycidol ether propyl trimethoxy silicane 56 μ l successively, be warming up to 85 DEG C and at this temperature magnetic agitation react 12 hours; In above-mentioned solution, add 3ml dry pyridine, 1.0ml3,5-dichlorophenyl isocyanate and at 85 DEG C stirring reaction 12 hours;
4, resulting materials oxolane in 3 is fully washed, remove the derivative of non-bonding, obtain bonding type cellulose 2,3-bis-(3,5-dimethylphenylcarbamate)-6-(3,5-dichlorophenyl carbamate) chiral stationary phase.
Embodiment 5
1, get 0.21g2,3-bis-(3,5-dichlorophenyl carbamate)-6-hydroxylated cellulose, adds 5ml pyridine, and vibration makes it dissolve;
2, gained solution in 1 is coated on 1.0g silica gel, by methanol wash 4 times, each 40ml; By above-mentioned material in 80 DEG C of baking ovens dry 4 hours;
3, resulting materials 0.75g in 2 is proceeded to be equipped with in two neck round-bottomed flasks of nitrogen protection device, add 5ml dry toluene, magnetic agitation makes silica gel fully suspend, then under room temperature, add boron trifluoride etherate 3.5 μ l, 3-glycidol ether propyl trimethoxy silicane 56 μ l successively, be warming up to 85 DEG C and at this temperature magnetic agitation react 12 hours; In above-mentioned solution, add 3ml dry pyridine, 1.0ml3,5-dimethylphenyl isocyanate and at 85 DEG C stirring reaction 12 hours;
4, resulting materials oxolane in 3 is fully washed, remove the derivative of non-bonding, obtain bonding type cellulose 2,3-bis-(3,5-dichlorophenyl carbamate)-6-(3,5-dimethylphenylcarbamate) chiral stationary phase.
Above-described embodiment is only preferred embodiment of the present invention, not limits the scope of the invention according to this, therefore: all equivalence changes done according to structure of the present invention, shape, principle, all should be covered by within protection scope of the present invention.
Claims (7)
1. the preparation of bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase, is characterized in that:
By glucose unit 2-, 3-position is replaced by corresponding substituting group and the unsubstituted cellulose in 6-position or starch derivatives are coated on silica gel, then the silica gel being coated with derivative is suspended in dry organic solvent, add catalyst and bifunctional reagent's (containing epoxide group and silica-based group of tri-alkoxy) successively, epoxide group in bifunctional reagent and glucose unit 6-position hydroxyl are reacted and introduces the intermolecular polycondensation reaction of the concurrent life of the silica-based group of tri-alkoxy in 6-position, finally derive 6-position hydroxyl with corresponding reagent and prepare bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase.
2. preparation according to claim 1, its process is as follows:
1) by 0.10-0.40g glucose unit 2-, 3-position is replaced by corresponding substituting group and the unsubstituted cellulose in 6-position or starch derivatives are dissolved in the neat solvent of 5-20ml oxolane, acetone, chloroform, pyridine, DMA etc. or the mixed liquor of above-mentioned solvent;
2) said derivative solution is coated on 1.0g silica gel;
3) by step 2) resulting materials dry 2-8 hour at 60-100 DEG C in baking oven;
4) by step 3) resulting materials introduce be equipped with in the airtight container of nitrogen protection device, and add the organic solvent of 3-10ml drying, magnetic agitation makes silica gel fully suspend, then at 10-40 DEG C, catalyst and bifunctional reagent is added successively, and 2-12 hour is reacted at 50-100 DEG C, add the pyridine of 3-10ml drying and 0.1-1.0ml isocyanates or chlorobenzoyl chloride after reaction terminates and in 70-100 DEG C of reaction 12-24 hour, obtain bonding type regioselectivity modified polysaccharide analog derivative chiral stationary phase;
5) fully wash above-mentioned material with oxolane and/or pyridine and/or DMA and/or dimethyl sulfoxide (DMSO), remove the polysaccharide derivates of non-bonding.
3. preparation according to claim 2, is characterized in that: polysaccharide is cellulose, starch.
4. preparation according to claim 2, is characterized in that: during coating, the mass ratio of derivative and silica gel is 10%-40%.
5. preparation according to claim 2, it is characterized in that: step 4) organic solvent that adopts is dry toluene or benzene, bifunctional reagent is the similar compound of 3-glycidol ether propyl trimethoxy silicane, 3-glycidol ether propyl-triethoxysilicane or structure, and catalyst is the boron trifluoride complex such as boron trifluoride etherate, boron trifluoride tetrahydrofuran complex compound.
6. preparation according to claim 2, is characterized in that: the order that catalyst and bifunctional reagent add, for first to add catalyst, then adds bifunctional reagent; The temperature adding reaction system when catalyst and bifunctional reagent is 10-40 DEG C; After catalyst and bifunctional reagent finish, at 50-100 DEG C of reaction 2-12 hour.
7. preparation according to claim 2, it is characterized in that: the consumption of bifunctional reagent is the 10%-40% (mol ratio of polysaccharide, take glucose unit as benchmark), the consumption of catalyst is the 5%-50% (mol ratio) that bifunctional reagent measures.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109529794A (en) * | 2018-12-27 | 2019-03-29 | 中国人民解放军第四军医大学 | Optical pure mandel derivative-Cellulose chiral stationaryphase, preparation method and application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101259406A (en) * | 2007-12-17 | 2008-09-10 | 南京工业大学 | Preparation of bonding- affinity composite type polysaccharides chiral stationary phase |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101259406A (en) * | 2007-12-17 | 2008-09-10 | 南京工业大学 | Preparation of bonding- affinity composite type polysaccharides chiral stationary phase |
Non-Patent Citations (2)
| Title |
|---|
| SHOUWAN TANG ET AL.: "Immobilization of cellulose phenylcarbamate onto silica gel via intermolecular polycondensation of triethoxysilyl groups introduced with (3-glycidoxypropyl)triethoxysilane", 《J. SEP. SCI.》 * |
| TOMOYUKI IKAI ET AL.: "Immobilization of polysaccharide derivatives onto silica gel Facile synthesis of chiral packing materials by means of intermolecular polycondensation of triethoxysilyl groups", 《JOURNAL OF CHROMATOGRAPHY A》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109529794A (en) * | 2018-12-27 | 2019-03-29 | 中国人民解放军第四军医大学 | Optical pure mandel derivative-Cellulose chiral stationaryphase, preparation method and application |
| CN109529794B (en) * | 2018-12-27 | 2021-12-17 | 中国人民解放军第四军医大学 | Optical pure mandelic acid derivative-cellulose chiral stationary phase, preparation method and application |
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