Highly Efficient Synthesis of Optically Pure (S)‐1‐phenyl‐1,2‐ethanediol by a Self‐Sufficient Whole Cell Biocatalyst

Abstract

Terminal vicinal diols are important chiral building blocks and intermediates in organic synthesis. Reduction of α-hydroxy ketones provides a straightforward approach to access these important compounds. In this study, it has been found that asymmetric reduction of a series of α-hydroxy aromatic ketones and 1-hydroxy-2-pentanone, catalyzed by Candida magnolia carbonyl reductase (CMCR) with glucose dehydrogenase (GDH) from Bacillus subtilis for cofactor regeneration, afforded 1-aryl-1,2-ethanediols and pentane-1,2-diol, respectively, in up to 99 % ee. In order to evaluate the efficiency of the bioreduction, lyophilized recombinant Escherichia coli whole cells coexpressing CMCR and GDH genes were used as the biocatalyst and α-hydroxy acetophenone as the model substrate, and the reaction conditions, such as pH, cosolvent, the amount of biocatalyst and the presences of a cofactor (i.e., NADP+), were optimized. Under the optimized conditions (pH 6, 16 h), the bioreduction proceeded smoothly at 1.0 m substrate concentration without the external addition of cofactor, and the product (S)-1-phenyl-1,2-ethanediol was isolated with 90 % yield and 99 % ee. This offers a practical biocatalytic method for the preparation of these important vicinal diols.

Halogenated Compounds from Directed Fermentation of Penicillium concentricum, an Endophytic Fungus of the Liverwort Trichocolea tomentella

“…To isolate epoxydon-related and unrelated new and bioactive compounds, P. concentricum was cultured on rice and on halogen salt (KCl or KBr)-supplemented rice media for 14 days. Successive normal, reversed-phase open, and flash silica gel (C 18 ) and high-performance liquid chromatography (HPLC) separation of the ethyl acetate fraction of the defatted methanol extract of P. concentricum fermented on rice medium afforded a new chlorinated xanthone, 6-chloro-3,8-dihydroxy-1-methylxanthone ( 1 ), together with 15 known compounds, identified as epoxydon ( 4 ), − norlichexanthone ( 5 ), − gentisyl alcohol ( 9 ), gentisyl quinone ( 10 ), ( R,S )-1-phenyl-1,2-ethanediol ( 11 ), dehydro­dechlorogriseofulvin ( 12 ), dechlorogriseofulvin ( 13 ), dehydrogriseofulvin ( 14 ), griseofulvin ( 15 ), ethylene glycol benzoate ( 16 ), alternariol ( 17 ), , griseoxanthone C ( 18 ), , drimiopsin H ( 19 ), griseophenone C ( 20 ), and griseophenone B ( 21 ) . Ethyl acetate extracts of the same strain fermented on KBr and KCl salt supplemented rice media afforded 2-bromo­gentisyl alcohol ( 2 ), 2-chloro­gentisyl alcohol ( 6 ), , an epimeric mixture of cis - and trans -bromohydrins ( 3a , 3b ), and trans - and cis -chlorohydrins ( 8a , 8b ), , together with the four known compounds identified as 4 , 5 , 13 , and 15 .…”

Molecular Basis for the High Activity and Enantioselectivity of the Carbonyl Reductase from Sporobolomyces salmonicolor toward α-Haloacetophenones

“…22 LBADH showed higher enzyme activity toward the acetophenones with one or two hydrogen atoms being substituted with electronwithdrawing groups such as F, Cl, and Br, although the activity enhancement is not as significant as for SSCR (Table 1). SSCR showed a nearly 10-fold activity enhancement when the αposition of the substrate was substituted by a hydroxyl group (1h), 25 while LBADH exhibited the opposite trend. The acetophenones with monohalogenation were better substrates of LBADH than those with two halogen atoms at the α position because of the steric effect.…”

Highly selective resolution of racemic 1‐phenyl‐1,2‐ethanediol by a novel strain Kurthia gibsonii SC 0312

“…; Chen et al . ) and the asymmetric resolution of racemic diol by oxidase or lipase, etc. (Turner ; Tian et al .…”

“…The main approaches preparing chiral PED by biocatalysis include the hydrolysis of epoxides by epoxide Letters in Applied Microbiology 68, 446--454 © 2019 The Society for Applied Microbiology hydrolase (Wang et al 2017;Peng et al 2018), the reduction in prochiral ketone by reductase Chen et al 2015) and the asymmetric resolution of racemic diol by oxidase or lipase, etc. (Turner 2010;Tian et al 2011).…”