Abstract
(R)-p-chlorophenyl-1,2-ethanediol (pCPED) is an important intermediate for the synthesis of (R)-eliprodil that is widely applied in the treatment of ischemic stroke. To prepare (R)-pCPED with high enantiomeric excess (ee p) and yield via the enantioconvergent hydrolysis of racemic styrene oxide (rac-pCSO) at high concentration, the bi-enzymatic catalysis was designed and investigated by a pair of epoxide hydrolases, a mutant (PvEH1Z4X4-59) of Phaseolus vulgaris EH1 and a mutant (RpEHF361V) of Rhodotorula paludigena RpEH. Firstly, the maximum allowable concentration of rac-pCSO was confirmed. Subsequently, the addition mode and the weight ratio of two Escherichia coli cells were optimized. Finally, under the optimized reaction conditions—the cell weight ratio 20:1 of E. coli/pveh1z4x4-59 to E. coli/rpeh F361V, a simultaneous addition mode, and reaction temperature at 25°C—300 mM rac-pCSO in the 100 ml 4% (v/v) Tween-20/phosphate buffer system (100 mM, pH 7.0) was completely hydrolyzed within 5 h, affording (R)-pCPED with 87.8% ee p, 93.4% yield, and 8.63 g/L/h space–time yield (STY). This work would be an efficient technical strategy for the preparation of chiral vicinal diols at industrial scale.
Highlights
Value-added chiral chemicals, such as epoxides and/or their corresponding vicinal diols, are versatile chiral building blocks applied in pharmaceuticals, fine chemicals, and agrochemical industries due to the fact that they can perform various chemical reactions with nucleophiles, electrophiles, acids, and bases (Zou et al, 2018)
RpEHF361V, preferentially hydrolyzing the (R)-pCSO with a main attack at a β-carbon atom, can enantioselectively hydrolyze rac-pCSO at high concentration (800 mM), affording (R)-pCPED and retaining (S)-pCSO with over 99% ees and 43.2% yield at 55.5% c in 12 h
The regioselectivity coefficients, quantitatively representing its regioselectivities for (S)-and (R)-pCSO, were used to elucidate the eep of (R)-pCPED produced from the enantioconvergent hydrolysis of rac-pCSO (Zhang et al, 2020)
Summary
Value-added chiral chemicals, such as epoxides and/or their corresponding vicinal diols, are versatile chiral building blocks applied in pharmaceuticals, fine chemicals, and agrochemical industries due to the fact that they can perform various chemical reactions with nucleophiles, electrophiles, acids, and bases (Zou et al, 2018). Enantioconvergent Hydrolysis for (R)-pCPED (EHs, EC 3.3.2.-), which widely exist in microorganisms, plants, invertebrates, and mammals, can stereoselectively catalyze the opening of an active three-membered oxirane ring of racemic epoxides, retaining epoxide enantiomers and/or producing enantiopure vicinal diols (Woo et al, 2015). Based on the catalytic mechanisms of the given EH–epoxide pairs, the asymmetric hydrolysis of rac-epoxides can be divided into two pathways: kinetic resolution and enantioconvergent hydrolysis (Bala and Chimni, 2010). Compared with the kinetic resolution having an intrinsic limitation of 50% maximum yield of epoxide enantiomers, the enantioconvergent hydrolysis can completely convert rac-epoxides into chiral vicinal diols with up to 100% theoretical yield (Wu et al, 2015)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
