Development of biocompatible DES/NADES as co-solvents for efficient biosynthesis of chiral alcohols

Advances in deep eutectic solvents and water: applications in metal- and biocatalyzed processes, in the synthesis of APIs, and other biologically active compounds

“…120 Similarly, four DESs and 13 NADESs have been screened in the bioreduction of 4-(trifluoromethyl)acetophenone (61) to (R)-1-[4-(trifluoromethyl)phenyl]ethanol (62) promoted by the recombinant E. coli LXCAR-S154Y and Geotrichum ZJPH1810 biocatalysts (Scheme 23). 121 Compound 62 is a key intermediate in the preparation of several pharmaceuticals, including the chemokine CCR5 antagonist, which is widely used for the treatment of AIDS, the DP1 receptor antagonist, and the antifungal econazole. 121 The desired secondary alcohol was isolated in high yields (up to 92.4%) and enantioselectivity (up to View Article Online >99%), also on a preparative scale.…”

“…121 Compound 62 is a key intermediate in the preparation of several pharmaceuticals, including the chemokine CCR5 antagonist, which is widely used for the treatment of AIDS, the DP1 receptor antagonist, and the antifungal econazole. 121 The desired secondary alcohol was isolated in high yields (up to 92.4%) and enantioselectivity (up to View Article Online >99%), also on a preparative scale. The best results were obtained when betaine (B), L-proline (Pro) and L-carnitine were used as HBAs in place of ChCl, with an improved catalytic efficiency due to the preservation of cell membrane integrity by the above DES components and an effective coenzyme regeneration.…”

“…A lower yield (77%) was observed when the biotransformation was carried out in an aqueous buffer system, with the same 400 mM substrate concentration. 121 Various NADESs have also been screened in the bioreduction of 2-chloro-1-(3,4-difluorophenyl)ethanone ( 63) to (S)-2chloro-1-(3,4-difluorophenyl)ethanol (64), which is a key chiral synthon for the synthesis of P2Y12 receptor antagonist Ticagrelor (Brilinta ® ), by the recombinant E. coli BL21 (DE3), expressing a carbonyl reductase from Leifsonia xyli HS0904. 122 Mixtures of ChCl salts and amino acids [e.g., ChCl/glycine (Gly), ChCl/glutathione (GSH), ChCl/Glc, ChCl/alanine (Ala), choline acetate (ChAc)/GSH, ChAc/glutamic acid (Glu)] were found to affect strongly the pH of the medium when amounts up to 1% w/v were added to cells suspension with respect to buffer solution, in many cases with a decreased reaction yield, probably due to a change of the binding of carbonyl reductase to the substrate.…”

Effective asymmetric preparation of (R)-1-[3-(trifluoromethyl)phenyl]ethanol with recombinant E. coli whole cells in an aqueous Tween-20/natural deep eutectic solvent solution

“…Biocatalytic reactions might be inhibited by the low mass-transfer efficiency and the toxicity of hydrophobic substrates/products toward the biocatalyst (Erol and Hollmann 2021 ; Jung et al 2013 ). It was reported that NADESs can improve the mass transfer efficiency by enhancing the permeability of cell membrane, and alleviate substrate/product inhibition (Xia et al 2020 ). In this work, twenty-two types of NADESs were introduced individually into the reaction medium to further improve the conversion efficiency.…”

“…The metabolic activity retention (MAR) value of recombinant E. coli cells was assessed by the method recorded in our previous research (Xia et al 2020 ). The cells were pre-incubated for 6 h at 30 ºC and 200 rpm in a buffer solution containing surfactant or NADES, with 3'-(trifluoromethyl)acetophenone or not.…”