Extreme halophilic alcohol dehydrogenase mediated highly efficient syntheses of enantiopure aromatic alcohols

Abstract

Enzymatic synthesis of enantiopure aromatic secondary alcohols (including substituted, hetero-aromatic and bicyclic structures) was carried out using halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii (HvADH2). This enzyme showed an unprecedented substrate scope and absolute enatioselectivity. The cofactor NADPH was used catalytically and regenerated in situ by the biocatalyst, in the presence of 5% ethanol. The efficiency of HvADH2 for the conversion of aromatic ketones was markedly influenced by the steric and electronic factors as well as the solubility of ketones in the reaction medium. Furthermore, carbonyl stretching band frequencies ν (C[double bond, length as m-dash]O) have been measured for different ketones to understand the effect of electron withdrawing or donating properties of the ketone substituents on the reaction rate catalyzed by HvADH2. Good correlation was observed between ν (C[double bond, length as m-dash]O) of methyl aryl-ketones and the reaction rate catalyzed by HvADH2. The enzyme catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that HvADH2 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.

Whole cell application of Lactobacillus paracasei BD101 to produce enantiomerically pure (S)‐cyclohexyl(phenyl)methanol

“…1 H and 13 C nuclear magnetic resonance (NMR) spectra were recorded on Bruker 400 MHz spectrometer in CDCl 3 . The growth mediums for bacterial growth were purchased from Merck.…”

“…1 The interaction of chiral compounds with chiral environments may result in biologically different enantiomers that may have deteriorative effects. 1 The interaction of chiral compounds with chiral environments may result in biologically different enantiomers that may have deteriorative effects.…”

“…Chemical catalysts might produce toxic waste and a large range of by-products, whereas biocatalysts are biodegradable products and provide a clean and environmentally friendly process to carry out these reactions under mild reaction conditions with high selectivity for the substrate. 1 Recently, we performed asymmetric reduction of acetophenones and piperonyl methyl ketone by high enantioselectivity and conversion using Lactobacillus paracasei BD101 as biocatalyst. 17 Whole cell biocatalysts compared with the pure enzyme are advantageous as they are usually cheap and more stable.…”

Synthesis of enantiopure (S)‐6‐chlorochroman‐4‐ol using whole‐cell Lactobacillus paracasei biotransformation

“…The production of enantiomerically pure chroman‐4‐amines are substantial since they can be used as core staging in drug estimation programs . It has been reported in the literature that bioreduction of fused cyclic ketones such as chroman‐4‐one using pure enzyme is difficult . On the other hand, bioreduction of 6‐fluorochroman‐4‐one, using whole‐cell Rhizopus arrhizus was carried out and furnished enantiomerically pure form in high yield .…”

“…19 It has been reported in the literature that bioreduction of fused cyclic ketones such as chroman-4-one using pure enzyme is difficult. 20,21 On the other hand, bioreduction of 6-fluorochroman-4-one, using whole-cell Rhizopus arrhizus was carried out and furnished enantiomerically pure form in high yield. 19 In the literature, the synthesis of (S)-6-chlorochroman-4-ol 2 was achieved by 50% yield and 80.4% enantiomeric excess (ee) in the presence of lipase enzyme 22 and other biocatalysis.…”