Insight into microwave irradiation and enzyme catalysis in enantioselective resolution of RS‐( ± )‐methyl mandelate
Background: Mandelic acid enantiomers are important chiral analogs used for the resolution of racemic alcohols and amines. R-(−)-mandelic acid is a precursor for the production of semi-synthetic penicillins and cephalosporins and also for the synthesis of various pharmaceuticals. Production of optic...
| Main Authors: | , , |
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| Format: | Article in Journal/Newspaper |
| Language: | unknown |
| Published: |
John Wiley & Sons, Inc
2008
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| Subjects: | |
| Online Access: | http://repository.ias.ac.in/111653/ http://onlinelibrary.wiley.com/doi/10.1002/jctb.1975/abstract |
| Summary: | Background: Mandelic acid enantiomers are important chiral analogs used for the resolution of racemic alcohols and amines. R-(−)-mandelic acid is a precursor for the production of semi-synthetic penicillins and cephalosporins and also for the synthesis of various pharmaceuticals. Production of optically pure mandelic acid enantiomers is commercially significant. This work deals with the resolution of RS-( ± )-methyl mandelate to produce optically pure R-(−)-mandelic acid in non-aqueous media via lipase-catalyzed hydrolysis under microwave irradiation. Results: Among three commercial lipases, Novozym 435 (Candida antartica B immobilized on macroporous polyacrylate resin) was found to be the most effective in the selective hydrolysis of R-(−)-methyl mandelate to R-(−)-mandelic acid from the racemic mixture of RS-( ± )-methyl mandelate, with an optical purity (ee p ) of 84.2% after 4 h at 50 °C. The effects of various parameters were studied to arrive at the optimum parameters and kinetics. The optimum catalyst loading was found to be 5 mg cm -3 at a concentration of 0.25 mmol cm -3 each of methyl mandelate and water. Based on the initial rate studies and concentration profiles, a complete rate equation is proposed, which includes the irreversible inactivation caused by RS-( ± )-methyl mandelate, and it follows the ternary complex mechanism with dead end inhibition by RS-( ± )-methyl mandelate. Conclusion: Novozym 435 is the most active lipase for resolution of R-(−)-mandelic acid from RS- ( ± )-methyl mandelate in tert-butanol. Various equilibrium constants were evaluated and simulations were performed giving excellent agreement between the two. |
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