Regioselective asymmetric bioreduction of trans‐4‐phenylbut‐3‐en‐2‐one by whole‐cell of Weissella cibaria N9 biocatalyst

Abstract

There is a considerable interest in the asymmetric production of chiral allylic alcohols, the main building blocks of many functional molecules. The asymmetric reduction of α,β-unsaturated ketones is difficult with traditional chemical protocols in a regioselective and stereoselective manner. In this study, the reductive capacity of whole cell of Leuconostoc mesenteroides N6, Weissella paramesenteroides N7, Weissella cibaria N9, and Leuconostoc pseudomesenteroides N13 was investigated as whole-cell biocatalysts in the enantioselective reduction of (E)-4-phenylbut-3-en-2-one (1). The biocatalytic reduction of 1 to (S,E)-4-phenylbut-3-en-2-ol ((S,E)-2) using the whole cell of W. cibaria N9 isolated from Turkish sourdough was developed in a regioselective fashion, occurring with excellent conversion and recovering the product in good yield. In biocatalytic reduction reactions, the conversion of the substrate and the enantiomeric excess (ee) of the product are significantly affected by optimization parameters such as temperature, agitation rate, pH, and incubation time. Effects of these parameters on ee and conversion were investigated comprehensively. In addition, to our knowledge, this is the first report on production of (S,E)-2 using whole-cell biocatalyst in excellent yield, conversion with enantiopure form and at gram scale. These findings pave the way for the use of whole cell of W. cibaria N9 for challenging higher substrate concentrations of different α,β-unsaturated ketones for regioselective reduction at industrial scale.

Gram‐scale synthesis of (S)‐1‐(thiophen‐2‐yl)ethanol in high enantiomeric purity under Enterococcus faecium BY48 biocatalysts

“…To achieve this, reaction conditions must be set up in such a manner that a reactant may be transported to catalytic sites with the maximum solubility in the reaction media, hence increasing the permeability of the cells to the reactant. The success of a biocatalytic process, in terms of yield and enantiomeric purity of the desired product, is dependent on both the accurate selection of the best performing biocatalyst and the optimization of reaction parameters 26 . First of all, to determine the biocatalyst with the best reducing capacity, six different biocatalysts were tested in the asymmetric reduction of substrate 1 (Table 1).…”

Biocatalytic asymmetric synthesis of secondary allylic alcohols using Burkholderia cepacia lipase immobilized on multiwalled carbon nanotubes

“…Chemical stereoselective methods are available for the synthesis of pure enantiomers of allylic alcohols, including reduction of prochiral ketones 8,12 and hydrogenation of enones 13 . However, these methods are not particularly practical due to the use of high temperatures and pressure and argon atmosphere; moreover, the catalytic process involves a metal ligand 5,12,13 …”

“…Their utility has been largely demonstrated in a variety of organic transformations, including the formation of carbon-carbon bonds and the addition of several functional groups into the double bond, incorporating other stereocenters through reactions of hydrogenation, epoxidation, and hydroboration, such as Simmons-Smith reaction. [1][2][3][4][5][6][7][8] Furthermore, optically active allylic alcohols can serve as building blocks in the synthesis of chiral lactones, such as 4-hydroxy-5-6-dihydropyrone, which has inhibitory activity against the HIV protease. 9,10 Beyond this, some allylic alcohols are used in the synthesis of enantiomerically pure hydroxy lactones, which exhibited high antifeedant activity against insects.…”

“…Enantiopure allylic alcohols are versatile building blocks for asymmetric synthesis and exist in a wide range of natural products. Their utility has been largely demonstrated in a variety of organic transformations, including the formation of carbon–carbon bonds and the addition of several functional groups into the double bond, incorporating other stereocenters through reactions of hydrogenation, epoxidation, and hydroboration, such as Simmons–Smith reaction 1–8 . Furthermore, optically active allylic alcohols can serve as building blocks in the synthesis of chiral lactones, such as 4‐hydroxy‐5‐6‐dihydropyrone, which has inhibitory activity against the HIV protease 9,10 .…”

“…9,10 Beyond this, some allylic alcohols are used in the synthesis of enantiomerically pure hydroxy lactones, which exhibited high antifeedant activity against insects. 11 Chemical stereoselective methods are available for the synthesis of pure enantiomers of allylic alcohols, including reduction of prochiral ketones 8,12 and hydrogenation of enones. 13 However, these methods are not particularly practical due to the use of high temperatures and pressure and argon atmosphere; moreover, the catalytic process involves a metal ligand.…”