Selectivity enhancement of enantio- and stereo-complementary epoxide hydrolases and chemo-enzymatic deracemization of (±)-2-methylglycidyl benzyl ether |
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| Institution: | 1. Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden;2. Department of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23 Uppsala, Sweden;1. Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy;2. KemoTech, KemoTech s.r.l., Parco Scientifico della Sardegna, Edificio 3, Loc. Piscinamanna, 09010 Pula (CA), Italy;3. Dipartimento di Chimica e Farmacia dell’Università degli Studi di Sassari, Via F. Muroni 23/A, 07100 Sassari (SS), Italy;4. C.N.R.—Istituto di Farmacologia Traslazionale, Parco Scientifico della Sardegna, Edificio 5, Loc. Piscinamanna, 09010 Pula (CA), Italy;5. C.N.R.—Istituto di Chimica del Riconoscimento Molecolare, Sezione ‘A. Quilico’, Via Mancinelli 7, 20131 Milano, Italy;6. Kosterlitz Centre for Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK;1. Núcleo de Espectroscopia e Estrutura Molecular (NEEM), Departamento de Química, Universidade Federal de Juiz de Fora, Campus Universitário s/n, Martelos, Juiz de Fora, MG, 36036-900, Brazil;2. School of Life Sciences, University of Bradford, Bradford, BD7 1DP, West Yorkshire, UK |
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| Abstract: | The kinetic resolution of (±)-2-methylglycidyl benzyl ether was achieved via enantioselective biohydrolysis using microbial and plant epoxide hydrolases. Depending on the type of enzyme, opposite enantiopreference and stereo-complementary mode of action (i.e., retention vs inversion of configuration) led to hetero- and homochiral product mixtures. Optimization of the reaction conditions for Rhodococcus sp. R312 led to significantly enhanced enantioselectivity (E >200), which enabled the deracemization of (±)-2-methylglycidyl benzyl ether via biohydrolysis (proceeding with retention of configuration) followed by inverting acid-catalyzed hydrolysis to furnish (R)-1-benzyloxy-2-methylpropane-2,3-diol in >97% ee and 78% yield from the racemate. |
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