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Chiral chromatographic fixed phase stuffing of vancomycin phenylisocyanate and its prepn

A technology of phenyl isocyanate and vancomycin, applied in the field of analytical chemistry, can solve the problems such as few separation reports, the separation effect does not reach the baseline separation and the like

Inactive Publication Date: 2006-05-17
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are few reports on the separation of the enantiomers of lamivudine in the literature, and it is only found that cyclodextrin derivatives are used as chiral additives or chiral stationary phases and bio-enzyme catalyzed methods for separation [Manus M.Rogan, ChristopherDrake , David M. Goodall, Kevin D. Altria. Enantioselective Enzymatic Biotransformation of 2`-Deoxy-3`-thiacytidine (BCH 189) Monitored by Capillary Electrophoresis. Anal. Biochem., 1993, 208: 343-347; Jonathan A.V. Coates, Nicholas Cammack, Helen J. Jenkinson, Ian M. Mutton, Bridget A. Pearson, Richard Storer, Janet M. Cameron, Charles R. Penn. The Separated Enantiomers of 2`-Deoxy-3`-Thiacytidine (BCH 189) Both Inhibit Human Immunodeficiency Virus Replication In Vitro. Antimicrob. Agents Chemiother. 1992, 36: 202-205; Jonathan A.V. Coates, Nicholas Cammack, Helen J. Jenkinson, Amanda J. Jowett, Michael I. Jowett, Bridget A. Pearson, Charles R. Penn, Philippa L. Rouse, K.Claire Viner, Janet M.Cameron.(-)-2`-Deoxy-3`-Thiacytidine Is a Potent, Highly Selective Inhibitor of Human Immunodeficincy Virus Type 1 and Type 2 Replication In Vitro.Antimicrob.Agents Chemiother.1992 , 36:733-739], but the separation effect has not reached the baseline separation, and when lamivudine is exported as an intermediate, the other enantiomer needs to be controlled below 0.3%, and the US Pharmacopoeia recommends the use of cyclodextrin chiral chromatography Columns are split, but cannot be baseline separated due to , the error is large for the detection of components with low content

Method used

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  • Chiral chromatographic fixed phase stuffing of vancomycin phenylisocyanate and its prepn
  • Chiral chromatographic fixed phase stuffing of vancomycin phenylisocyanate and its prepn

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1) Silanization of carrier silica gel

[0032] Weigh 10 grams of Kromasil spherical silica gel carrier (particle size 5 μm, pore size 10 nm) with 3 mol L -1 After hydrochloric acid was refluxed for 4 hours, it was washed with water to neutrality, dried in vacuum, and 10ml of 3-aminopropyltriethoxysilane was added with anhydrous toluene as a solvent, then refluxed for 8 hours, cooled to room temperature, filtered, washed with toluene and methanol, Vacuum drying to obtain 3-aminopropyl silica gel;

[0033] 2) Synthesis of bonded chiral stationary phase

[0034] Take 3 grams of the above dried 3-aminopropyl silica gel, add it to anhydrous toluene, add 2ml of 1,6-diisocyanate n-hexane dropwise under ice bath and nitrogen protection, heat the mixture to 65°C for 2 hours, and cool to Remove the solvent and 1,6-diisocyanate n-hexane after room temperature, add 100ml of anhydrous pyridine solution containing 1g of vancomycin, stir and react at 65°C for 10 hours under nitrogen...

Embodiment 2

[0036] 1) Silanization of carrier silica gel

[0037] Weigh 10 grams of Lichrosorb amorphous silica gel carrier (particle size 5 μm, pore size 10 nm) with 5 mol L -1 Hydrochloric acid was refluxed for 6 hours, washed with water until neutral, dried in vacuum, using anhydrous toluene as solvent, added 3-aminopropyltriethoxysilane, refluxed for 10 hours, cooled to room temperature, filtered, washed with toluene and methanol, and dried in vacuum Get 3-aminopropyl silica gel;

[0038] 2) Synthesis of bonded chiral stationary phase

[0039] Take 3 grams of the above-mentioned dry 3-aminopropyl silica gel, add it to anhydrous toluene, add 3ml of 1,6-diisocyanate n-hexane dropwise under ice bath and nitrogen protection, heat the mixture to 70°C for 3 hours, and cool to Remove the solvent and 1,6-diisocyanate n-hexane after room temperature, add 100ml of anhydrous pyridine solution containing 2g of vancomycin, stir and react at 70°C for 10 hours under nitrogen protection, filter, wa...

Embodiment 3

[0041] 1) Silanization of carrier silica gel

[0042] Weigh 10 grams of Lichrospher spherical silica gel carrier (particle size 5 μm, pore size 10 nm) with 5 mol L -1 Hydrochloric acid was refluxed for 4 hours, washed with water until neutral, dried in vacuo, using anhydrous toluene as solvent, added 3-aminopropyltriethoxysilane, refluxed for 8 hours, cooled to room temperature, filtered, washed with toluene and methanol, and dried in vacuo Get 3-aminopropyl silica gel;

[0043] 2) Synthesis of bonded chiral stationary phase

[0044] Take 3 grams of the above dried 3-aminopropyl silica gel, add it to anhydrous toluene, add 4ml of 1,6-diisocyanate n-hexane dropwise under ice bath and nitrogen protection, heat the mixture to 75°C for 3 hours, cool to Remove the solvent and 1,6-diisocyanate n-hexane after room temperature, add 100ml of anhydrous pyridine solution containing 2g of vancomycin, stir and react at 75°C for 12 hours under nitrogen protection, filter, and use pyridine...

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Abstract

The chiral chromatographic fixed phase stuffing of vancomycin phenylisocyanate is prepared through bonding vancomycin as glycopeptide macrocyclic antiseptic chemical onto silicon gel carrier, and the subsequent derivation of phenylisocyanate to obtain chiral chromatographic fixed phase stuffing. The silicon gel carrier is first reacted with 3-aminopropyl triethoxy silane for silanation and then space arm activated; and the activated silicon gel carrier is bonded with vancomycin and finally derivated with phenylisocyanate. The chiral chromatographic fixed phase stuffing of vancomycin phenylisocyanate after assembled to column may be used in forward phase, reverse phase and polar organic phase chromatographic condition. The present invention may be used in simple polar organic phase mode to resolve the medicine antimer of zolmitriptan, lamivudine, etc.

Description

technical field [0001] The invention relates to a vancomycin phenylisocyanate chiral chromatography stationary phase filler and a preparation method thereof. The stationary phase separates zolmitriptan and lamivudine drug enantiomers under polar organic phase conditions, and belongs to the field of analytical chemistry. Background technique [0002] Two chiral compounds that are enantiomers often have large differences in biological activity, pharmacokinetics, and potential side effects of drugs. About half of the western medicines currently on the market contain chiral centers. About half of them are sold in the form of racemates. For this reason, the health management departments of the United States, the European Community, Japan, Canada and other countries have put forward extremely strict requirements for new racemates, requiring their corresponding There is a clear description of the metabolism and pharmacokinetics of the body, and it is stipulated that any drug with ...

Claims

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Application Information

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IPC IPC(8): B01J20/29B01J20/30
Inventor 张大同徐秀珠
Owner ZHEJIANG UNIV
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