ŞAHIN
893
enantiomeric excess (ee) and a 99% yield.5 Lu and co-
workers demonstrated cobalt‐catalyzed asymmetric
hydrogenation of 1‐(benzofuran‐2‐yl)ethanone with 93%
ee using the chiral iminophenyl oxazolinylphenyl
amines ligands.6 The drawbacks of this method are the
expensive chiral reagent and environmental pollution.
The enantioselectivity of the product is related to
the complexity of the ligands. Some transition metals
need additional enantiomeric ligands to achieve high
enantioselectivity, and the cost of transition metals limits
the use of industrialization processes.7 Therefore, the
search for alternative biocatalytic processes for prepara-
tion of enantiomerically pure (S)‐1‐(benzofuran‐2‐yl) eth-
anol attracts more attention. An alternative way is the
enantioselective reduction of prochiral compounds using
enzymes or enzyme‐containing cells.8 In comparison with
the general chemical approach for chiral secondary alco-
hols synthesis, the biocatalytic method is more preferable
because of its high‐substrate specificity, mild reaction
conditions, and environmental sustainability. Biocatalysts
took advantage of high chemo‐, regio‐, unsurpassed selec-
tivity and observed the green principles.9 Furthermore,
the use of microbial whole cells with metabolic activity
as catalysts provides several merits over isolated enzymes,
including the cofactor recycling in situ and better pro-
tecting target enzymes against inactivation, thereby sig-
nificantly cutting down the process cost.10 Whole‐cell
biocatalysts, rather than purified enzymes, may be more
suitable for the large‐scale production, because microbial
whole cells used in production as catalysts contain multi-
ple active enzymes and better protects desired enzymes
against inactivation. Therefore, whole‐cell biocatalysts
provide an attractive alternative to selectively producing
corresponding single enantiomers. In addition, the ad-
vantage of the in situ recycle of cofactors reduces the pro-
cess cost, making it an increasingly attractive method for
biocatalysts.10-12 Asymmetric bioreduction of 2‐
acetylbenzo[b]furan with yeast biocatalyst gave (S)‐corre-
sponding alcohol with a moderate ee (55%) and in a mod-
erate yield (60%).13 Paizs and coworkers obtained (S)‐1‐
(benzofuran‐2‐yl)ethanol by 98.6% ee and 49% yield with
kinetic resolution of racemic benzofuran alcohol using
lipase biocatalysts.14 Although this yield is good for
kinetic resolution, it is low for asymmetric reduction.
The Rhizopus arrhizus mediated bioreduction of
1‐(benzofuran‐2‐yl)ethanone furnished 99.3% (S)‐1‐
(benzofuran‐2‐yl)ethanol, with 91.7% ee.15 In the litera-
ture, it has been reported that 1‐(benzofuran‐2‐yl)
ethanone is reduced to (R)‐benzofuran alcohol by 95%
ee and 47% yield with Daucus carota as biocatalyst.16 In
the present study, isolated Lactobacillus paracasei
BD87E617 was employed as a whole‐cell biocatalyst in
the asymmetric bioreduction of 1‐(benzofuran‐2‐yl)
ethanone to (S)‐1‐(benzofuran‐2‐yl)ethanol in an aqueous
medium (Figure 1).
Herein, we report the asymmetric bioreduction of
1‐(benzofuran‐2‐yl)ethanone 1 to the (S)‐1‐(benzofuran‐
2‐yl)ethanol 2 by L paracasei BD87E6 with 99.9% ee and
92% yields. Also, this is the first report on asymmetric
bioreduction of 1‐(benzofuran‐2‐yl)ethanone 1 using bio-
catalyst in the enantiopure form, excellent yield. Gram
scale bioreduction of 1‐(benzofuran‐2‐yl)ethanone 1 was
performed to the (S)‐1‐(benzofuran‐2‐yl) ethanol 2 in
enantiomerically pure form and excellent yield using L.
paracasei BD87E6 as a biocatalyst. The effects of some
key reaction parameters in terms of temperature, pH,
incubation period and agitation speed on the ee, conver-
sion, and yield were also optimized individually for the
reduction reaction.
2 | MATERIALS AND METHODS
2.1 | General
The substrate, bacterial growth medium (MRS), and sol-
vents were received from Fluka and Aldrich (purity of
>99%). The progress of reaction was checked by TLC,
using ethyl acetate: hexane (10:90, v/v) as the mobile
phase. Purification of (S)‐1‐(benzofuran‐2‐yl)ethanol was
performed by column chromatography filled with silica
gel (0.063‐0.2 mm), and the product was eluted with a
mixture of hexane: ethyl acetate (85:15, v/v). HPLC anal-
yses for substrate and product were performed on an
Agilent 1260 system combined with UV and chiral detec-
tor. Reference sample of racemic alcohol 2 was prepared
by reducing the ketone 1 with NaBH4 in methanol at
room temperature (RT). Optical rotation was determined
with a Bellingham + Stanley, ADP220, 589‐nm spectro-
polarimeter. The NMR spectra of the product were
detected by a Bruker spectrometer (Ascend TM; Bruker
Ltd., Germany). (S)‐1‐(benzofuran‐2‐yl)ethanol18: light
yellow liquid, isolated yield 92%, 1H NMR (400 MHz,
CDCl3) δ = 7.55‐7.52 (m, 1H), 7.48‐7.44 (m, 1H), 7.29‐
7.19 (m, 1H), 7.24‐7.20 (m, 1H), 6.61 (s, 1H), 5.02 (q, J
= 6.5, Hz, 1H), 2.19 (bs, 1H (OH)), 1.64 (d, J = 6.5, Hz,
3H); 13C NMR (100 MHz, CDCl3) δ = 160.2, 154.7,
25
128.1, 124.2, 122.8, 121.1, 111.2, 101.8, 64.2, 21.4; [α]D
FIGURE 1 Asymmetric production of
(S)‐1‐(benzofuran‐2‐yl)ethanol