Stereospecific enzymatic hydrolysis of racemic epoxide: a process for making chiral epoxide |
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| Institution: | 1. Enzyme Technology, Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, NJ 08903, USA;2. Process Technology, Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, NJ 08903, USA;1. Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, United States;2. Department of Biology, Eberly College of Arts and Sciences, West Virginia University, Morgantown, WV 26506, United States;3. Department of Integrative Medical Sciences, College of Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, United States;1. Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM) Università degli Studi di Messina, Viale Annunziata, I-98168 Messina, Italy;2. Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Viale Europa Località Germaneto, I-88100 Catanzaro, Italy;1. Departments of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA;2. Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA;3. Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA;4. Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA |
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| Abstract: | Among various microbial cultures evaluated, Rhodotorula glutinis SC 16293 and Aspergillus niger SC 16311 catalyzed the stereospecific hydrolysis of the racemic epoxide, RS-1-{2′,3′-dihydrobenzob]furan-4′-yl}-1,2-oxirane, 1 to the corresponding R-diol, R-1-{2′,3′-dihydrobenzob]furan-4′-yl}-ethane-1,2-diol, 3. The S-epoxide, S-1-{2′,3′-dihydrobenzob]furan-4′-yl}-1,2-oxirane, 2 remained unreacted in the reaction mixture. A reaction yield of 45–50% (theoretical maximum yield is 50%) and an enantiomeric excess (ee) of >95% were obtained for unreacted S-epoxide 2 using each culture. Addition of 10% methyl tert-butyl ether to an aqueous reaction mixture during hydrolysis by R. glutinis improved the ee of the unreacted S-epoxide 2 to >99% (yield 48%) and that of the R-diol 3 to 79%. Unlike R. glutinis, hydrolysis of racemic epoxide 1 in the presence of 10% methyl tert-butyl ether by A. niger showed an adverse effect and gave S-epoxide 2 in 54% yield and 49% ee. |
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