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Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids
Published on: June 28, 2019
Preparative resolution of etodolac enantiomers by preferential crystallization method
Phan Thanh Dung1, Tran Quoc Trung, Kyeong Ho Kim
1College of Pharmacy, Kangwon National University, Chuncheon, Korea.
Archives of Pharmacal Research
|November 10, 2009
Summary
This study developed a novel method for separating etodolac enantiomers using preferential crystallization, achieving high purity for both S-(+)-etodolac and R-(-)-etodolac. The efficient process yields pure enantiomers crucial for pharmaceutical applications.
Area of Science:
- Chemical Engineering
- Organic Chemistry
- Pharmaceutical Science
Background:
- Chiral compounds, such as etodolac enantiomers, are vital in various industries, particularly pharmaceuticals.
- Efficient separation of enantiomers is crucial for developing stereospecific drugs with improved efficacy and reduced side effects.
- Classical resolution methods often require optimization for industrial-scale enantiomer separation.
Purpose of the Study:
- To establish an effective method for separating etodolac enantiomers.
- To utilize preferential crystallization of etodolac derivatives for enantiomeric separation.
- To achieve high enantiomeric purity and yield for both S-(+)-etodolac and R-(-)-etodolac.
Main Methods:
- Preparation of etodolac enantiomers via classical resolution using diastereoisomeric salts with (-)-brucine and (-)-cinchonidine.
- Formation of conglomerate derivatives of etodolac to enable preferential crystallization.
- Determination of enantiomeric purity using High-Performance Liquid Chromatography (HPLC) with a Chiralcel OD-H column.
- Fractionation of pure diastereomeric salts into enantiomers through liquid-liquid extraction.
Main Results:
- Successful separation of S-(+)-etodolac and R-(-)-etodolac enantiomers was achieved.
- Enantiomeric purity exceeding 99.9% was obtained for both separated enantiomers.
- The overall yield for the recovered etodolac enantiomers surpassed 20%.
Conclusions:
- The developed method, combining classical resolution with preferential crystallization, is highly effective for producing pure etodolac enantiomers.
- This technique offers a viable route for industrial-scale production of enantiomerically pure etodolac.
- The high purity and yield demonstrate the robustness and efficiency of the separation process.
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