- Enzyme-catalysed regio- and enantioselective preparative scale synthesis of (S)-2-hydroxy alkanones
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α-Hydroxy alkanones were synthesised with high enantiomeric purity by stereoselective enzyme-catalysed diketone reduction. Both diketone reduction and cofactor regeneration were accomplished with purified carbonyl reductase from Candida parapsilosis (CPCR2). The reaction products were isolated by column chromatography and analysed by chiral GC measurements, 1H-NMR spectroscopy and determination of optical rotations. Preparative-scale biotransformations yielded 350-600 mg of pure aliphatic α-hydroxy ketones including the difficult to obtain (S)-2-hydroxypentane-3-one. For all the products good enantiomeric excesses in the range of 89-93% were achieved.
- Loderer,Ansorge-Schumacher
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- Assessing the stereoselectivity of: Serratia marcescens CECT 977 2,3-butanediol dehydrogenase
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α-Hydroxy ketones and vicinal diols constitute well-known building blocks in organic synthesis. Here we describe one enzyme that enables the enantioselective synthesis of both building blocks starting from diketones. The enzyme 2,3-butanediol dehydrogenase (BudC) from S. marcescens CECT 977 belongs to the NADH-dependent metal-independent short-chain dehydrogenases/reductases family (SDR) and catalyses the selective asymmetric reductions of prochiral α-diketones to the corresponding α-hydroxy ketones and diols. BudC is highly active towards structurally diverse diketones in combination with nicotinamide cofactor regeneration systems. Aliphatic diketones, cyclic diketones and alkyl phenyl diketones are well accepted, whereas their derivatives possessing two bulky groups are not converted. In the reverse reaction vicinal diols are preferred over other substrates with hydroxy/keto groups in non-vicinal positions.
- Médici, Rosario,Stammes, Hanna,Kwakernaak, Stender,Otten, Linda G.,Hanefeld, Ulf
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p. 1831 - 1837
(2017/07/15)
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- Promiscuous substrate binding explains the enzymatic stereoand regiocontrolled synthesis of enantiopure hydroxy ketones and diols
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Regio- and stereoselective reductions of several diketones to afford enantiopure hydroxy ketones or diols were accomplished using isolated alcohol dehydrogenases (ADHs). Results could be rationalised taking into account different (promiscuous) substrate-binding modes in the active site of the enzyme. Furthermore, interesting natural cyclic diketones were also reduced with high regio- and stereoselectivity. Some of the 1,2 and 1,3-diketones used in this study were reduced by employing a low excess of the hydrogen donor (2-propanol) due to the quasi-irreversibility of these ADH-catalysed processes. Thus, using lower quantities of co-substrate, scale-up could be easily achieved.
- Kurina-Sanz, Marcela,Bisogno, Fabricio R.,Lavandera, Ivan,Orden, Alejandro A.,Gotor, Vicente
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experimental part
p. 1842 - 1848
(2011/02/25)
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- Deracemization of (±)-2,3-disubstituted oxiranes via biocatalytic hydrolysis using bacterial epoxide hydrolases: Kinetics of an enantioconvergent process
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Asymmetric biocatalytic hydrolysis of (±)-2,3-disubstituted oxiranes leading to the formation of vicinal diols in up to 97% ee at 100% conversion was accomplished by using the epoxide hydrolase activity of various bacterial strains. The mechanism of this deracemization was elucidated by 18OH2-labelling experiments using a partially purified epoxide hydrolase from Nocardia EH1. The reaction was shown to proceed in an enantioconvergent fashion by attack of OH- at the (S)-configured oxirane carbon atom with concomitant inversion of configuration. A mathematical model developed for the description of the kinetics was verified by the determination of the four relative rate constants governing the regio- and enantio-selectivity of the process.
- Kroutil, Wolfgang,Mischitz, Martin,Faber, Kurt
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p. 3629 - 3636
(2007/10/03)
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- 107. Silicon-Directed Regio- and Enantioselective Synthesis of α-Hydroxy-ketones
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α-Silylated ketones (S)-2 (ee >/= 98percent), easily available through silylation or silylation/alkylation from ketones 1 using the (-)-(S)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP)-/(+)-(R)-1-amino-2-(methoxymethyl)pyrrolidine (RAMP)-hydrazone method, are oxidized to give α-hydroxy-ketones (R)-5 of high enantiomeric purity (ee >/= 98percent) and in good overall yields (51-70percent).The key step of the procedure is the silicon-directed diastereoselective oxidation of the corresponding silyl enol ethers of (S)-2, with m-chloroperbenzoic acid or 3-phenyl-2-(phenylsulfonyl)oxaziridine, followed by flash chromatography and desilylation.
- Lohray, Braj B.,Enders, Dieter
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p. 980 - 984
(2007/10/02)
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