Asymmetric synthesis of α-bromohydrins by carrot root as biocatalyst and conversion to enantiopure β-hydroxytriazoles and styrene oxides using click chemistry and SN2 ring-closure

Article abstract of DOI:10.1007/s13738-018-1535-4

In this study we have combined the bioreduction of α-bromoketones using carrot root as biocatalyst and click chemistry for the preparation of enantiopure β-hydroxytriazoles in excellent enantiomeric excesses and yields. Moreover, we have utilized chiral α-halohydrins for the synthesis of enantiopure styrene oxides in very good yields and enantiomeric excesses. Structural assignments of the products were based on their ¹H and ¹³C NMR data and their optical rotations. The enantiomeric excess of the chiral products was obtained by HPLC analysis.

Full text of DOI:10.1007/s13738-018-1535-4

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1535-4
ORIGINAL PAPER
Asymmetric synthesis of α-bromohydrins by carrot root as biocatalyst
and conversion to enantiopure β-hydroxytriazoles and styrene oxides
using click chemistry and S 2 ring-closure
N
Rahman Hosseinzadeh1 · Maryam Mohadjerani · Sakineh Mesgar
2
1
Received: 20 May 2018 / Accepted: 22 October 2018
©
Iranian Chemical Society 2018
Abstract
In this study we have combined the bioreduction of α-bromoketones using carrot root as biocatalyst and click chemistry for
the preparation of enantiopure β-hydroxytriazoles in excellent enantiomeric excesses and yields. Moreover, we have utilized
chiral α-halohydrins for the synthesis of enantiopure styrene oxides in very good yields and enantiomeric excesses. Structural
1
13
assignments of the products were based on their H and C NMR data and their optical rotations. The enantiomeric excess
of the chiral products was obtained by HPLC analysis.
Keywords Bioreduction · Biocatalyst · Carrot root · Chiral α-halohydrins · Chiral β-hydroxytriazoles · Chiral styrene
oxides
Introduction
Jacobsens direct epoxidation of styrenes using (salen) Mn
complexes [18, 19] and enzymatic kinetic resolution of race-
mic epoxides [20–23]. The catalytic asymmetric reduction
of α-haloketones to the corresponding halohydrins via chiral
organo catalysts [24, 25] or biocatalysts [26–32] followed by
β-Hydroxy 1,2,3-triazoles are particularly interesting, not
only due to possessing 1,2,3-triazole structural scaffold
which has proven to exhibit interesting biological proper-
ties such as antibacterial, antiviral, antiepileptic, and anti-
allergic activities [1–5] but also as β-adrenergic receptor
blocker analogues [6] and as HIV-1 protease inhibitors [7,
base catalyzed S 2 ring-closure can be an effective approach
N
to achieve the chiral epoxides.
The use of plant as a whole living cell system in organic
biotransformation, especially for asymmetric reduction
has been continuously increasing over the past decade
[33]. Compared to isolated enzymes involved in reduc-
tion (alcohol-dehydrogenases ADHs), these systems do not
require cofactors and cofactor regeneration systems since
they already have these requirements. In addition, plants are
easily obtainable from markets and easily manipulated by
organic chemists in a laboratory without special equipment.
Besides, they may be edible and be therefore more suitable
for being used in food or pharmaceuticals industry [34, 35].
Carrot (Daucus carota) roots has been shown to reduce ace-
tophenones [36, 37] and other ketones [38, 39] with excel-
lent selectivity. We have recently studied the bioreduction
of carbonyl compounds by carrot [40–42]. In continuation
of our studies on developing an efficient method for the
preparation of several chiral compounds, we set out now to
probe the bioreduction of α-bromoketones to enantiopure
α-bromohydrins using carrot root as biocatalyst. The desired
8
]. Recently, a few procedures have been reported for the
synthesis of chiral β-hydroxytriazoles by the reaction of
sodium azide with chiral epoxides [9, 10] or α-haloketones
[
11, 12] followed by click reaction with terminal alkynes.
Enantiomerically pure styrene oxides are important chiral
building blocks for pharmaceutically important compounds
such as the antidepressant Sertraline, the adrenergic blockers
Nifenalol and Salmeterol, antiviral agents, and some kinase
inhibitors [13–15]. Among the approaches developed for
the preparation of chiral styrene oxides, we can mention
sharpless asymmetric dihyroxylation of styrenes [16, 17],
*
Rahman Hosseinzadeh
r.hosseinzadeh@umz.ac.ir
1
2
Department of Organic Chemistry, Faculty of Chemistry,
University of Mazandaran, Babolsar, Iran
Department of Molecular and Cell Biology, Faculty of Basic
Science, University of Mazandaran, Babolsar, Iran
Vol.:(0
1
123456789)
3

Journal of the Iranian Chemical Society
products were utilized in the synthesis of chiral styrene
(R)-2-Bromo-1-(4′-bromophenyl) ethanol (2a)
oxides and chiral β-hydroxytriazoles.
1
H NMR (400 MHz, CDCl ): δ=7.86 (dt, J=8.8, 2.0 Hz,
3
2
H, Ar H), 7.66 (dt, J= 8.8, 2.0 Hz, 2H, Ar H), 4.70 (dd,
J = 8.0, 2.8 Hz, 1H, CH), 3.88 (dd, J = 14.0, 8.0 Hz, 1H,
CH ), 3.82 (dd, J = 14.0, 2.8 Hz, 1H, CH ), 2.58 (br s,
Materials and methods
2
2
1
3
1
H, OH). C NMR (100 MHz, CDCl ): δ = 139.27 (C ),
3 q
All reagents and chemicals were purchased from commer-
cial sources and were used without further purification. The
starting phenacyl bromides were prepared from the corre-
sponding acetophenones by bromination method [43]. Fresh
carrot roots were purchased from a local market. The exter-
nal layer of roots was removed and the rest was carefully
cut into small thin pieces (approximately 5 mm × 5 mm
132.50 (Ar C), 128.45 (Ar C), 122.37 (C ), 80.66 (CH),
q
2
5
36.38 (CH ). [α] = −34.9 (c 1.00 in CHCl ) [lit. −42.7°,
2
D
3
c 0.5102 in CHCl ] [45], mp: 73 °C [46], retention times
3
(min): 12.95 (S), 16.78 (R).
(R)-2-Bromo-1-(3′-chlorophenyl) ethanol (3a)
1
×
2 mm). All melting points were measured on a Thermo
H NMR (400 MHz, CDCl ): δ=7.14 (d, J=8.4 Hz, 1H, Ar
3
1
13
scientific model 9100. The H and C NMR spectra were
H), 7.13–7.09 (m, 2H, Ar H), 6.99–6.97 (m, 1H, Ar H), 4.62
(dd, J=3.6, 3.2 Hz, 1H, CH), 3.78 (dd, J=14.1, 3.6 Hz, 1H,
CH ), 3.63 (dd, J=14.1, 3.2 Hz, 1H, CH ), 2.49 (br s, 1H,
registered in CDCl with a Bruker Avance ІІІ 400 MHz
3
spectrometer using TMS as internal standard. Optical rota-
tions were measured with a Kruess, P3001 polarimeter. The
enantiomeric excess of the chiral products was obtained
by HPLC with chiral column Chiralpak AS-H (25 cm ×
2
2
1
3
OH). C NMR (100 MHz, CDCl ): δ=140.47 (C ), 134.53
3
q
(Ar C), 129.60 (Ar C), 128.02 (Ar C), 127.50 (Ar C), 126.45
2
5
(C ), 82.80 (CH), 35.21 (CH ). [α]
= −37.4° (c 0.50 in
CHCl ) [lit. −22.10°, c 0.9671 in CHCl ] [45], colorless oil,
q
2
D
4
.6 mm) and mobile phase, n-hexane/isopropanol (80:20)
3
3
with flow rate 0.5 mL/min at a wavelength of 241 nm.
retention times (min): 10.19 (S), 11.54 (R).
(R)-2-Bromo-1-(4′-chlorophenyl) ethanol (4a)
General method for the asymmetric bioreduction
of α‑bromoketones 1–6 using Daucus carota
1
H NMR (400 MHz, CDCl ): δ=7.85 (dt, J=8.8, 2.4 Hz,
3
2
H, Ar H), 7.66 (dt, J= 8.8, 2.4 Hz, 2H, Ar H), 4.51 (dd,
α-Bromoketones (1.0 mmol) were added to a suspension
of freshly cut D. carota roots (17 g) in 100 mL of distilled
water and the reaction mixtures were incubated in an orbital
shaker (150 rpm) at 30 °C. The progress of the reaction was
monitored by TLC or by GC. After completion of the reac-
tion, the suspensions were filtered off and the carrot root
was washed successively with water. Filtrates were extracted
J = 3.2, 2.4 Hz, 1H, CH), 3.67 (dd, J = 12.4, 3.2 Hz, 1H,
CH ), 3.63 (dd, J=12.4, 2.4 Hz, 1H, CH ), 2.38 (br s, 1H,
2
2
1
3
OH). C NMR (100 MHz, CDCl ): δ=137.56 (C ), 134.70
3
q
(C ), 129.31 (Ar C), 127.87 (Ar C), 84.22 (CH), 35.08
q
2
5
(CH ). [α] = − 45.8° (c 2.1 in CHCl ); [lit. − 59.5° (c
2
D
3
0.9966 in CHCl )] [45], colorless oil, retention times (min):
3
11.56 (S), 12.30 (R).
with ethyl acetate (3×30 mL), dried on anhydrous MgSO
4
and concentrated under reduced pressure. The crude prod-
ucts were purified by column chromatography on silica gel
using ethyl acetate/n-hexane gradient to give the desired
products in high purity.
(R)-2-Bromo-1-(4′-methoxyphenyl) ethanol (5a)
1
H NMR (400 MHz, CDCl ): δ=7.83 (dt, J=9.0, 3.2 Hz,
3
2H, Ar H), 7.64 (dt, J= 9.0, 2.9 Hz, 2H, Ar H), 4.49 (dd,
J = 4.0, 3.6 Hz, 1H, CH), 3.81 (s, 3H, CH ), 3.65 (dd,
3
J=14.8, 3.6 Hz, 1H, CH ), 3.60 (dd, J=14.8, 4.0 Hz, 1H,
2
1
3
(R)-2-Bromo-1-phenylethanol (1a)
CH ), 2.36 (br s, 1H, OH). C NMR (100 MHz, CDCl ):
2
3
δ=159.31 (C ), 133.60 (C ), 129.90 (Ar C), 114.02 (Ar C),
q
q
1
25
H NMR (400 MHz, CDCl ): δ=8.00 (dt, J=8.2, 2.0 Hz,
79.90 (CH), 55.84 (CH ), 35.75 (CH ). [α]
= −41.9 (c
3
3
2
D
2
H, Ar H), 7.63 (tt, J =7.2, 2.0 Hz, 1H, Ar H), 7.56–7.48
0.5 in CHCl ) [lit. +36.7° (c 0.450 in CHCl ), for S isomer]
3
3
(
m, 2H, Ar H), 4.73 (dd, J=9.6, 3.6 Hz, 1H, CH), 3.88 (dd,
[47], colorless oil, retention times (min): 12.15 (S), 13.90
(R).
J=13.6, 9.6 Hz, 1H, CH ), 3.77 (dd, J=13.6, 3.6 Hz, 1H,
2
1
3
CH ), 2.60 (br s, 1H, OH). C NMR (100 MHz, CDCl ):
2
3
δ=140.10 (C ), 134.02 (Ar C), 128.96 (Ar C), 128.90 (Ar
(R)-2-Bromo-1-naphtylethanol (6a)
q
2
5
C), 81.71 (CH), 36.62 (CH ). [α]
= − 38.2° (c 1.00 in
2
D
1
CHCl ) [lit. + 39.80°, c 1.2 in CHCl for S isomer] [44],
H NMR (400 MHz, CDCl ): δ = 7.89–7.79 (m, 4H, Ar
3
3
3
colorless oil, retention times (min): 11.60 (S), 13.21 (R).
H), 7.56–7.49 (m, 3H, Ar H), 4.52 (dd, J=3.6, 3.4 Hz, 1H,
1
3

Journal of the Iranian Chemical Society
2
5
CH), 3.69 (dd, J=13.9, 3.6 Hz, 1H, CH ), 3.64 (dd, J=13.9,
[α]
= − 37.1° (c 1.00 in CHCl ), mp: 210–212 °C,
3
2
D
13
3
.4 Hz, 1H, CH ), 2.39 (br s, 1H, OH). C NMR: (100 MHz,
retention times (min): 28.3 (S), 30.5 (R).
2
CDCl ): δ=144.02 (C ), 134.62 (C ), 134.61 (C ), 128.74
3
q
q
q
(
Ar C), 128.51 (Ar C), 128.40 (Ar C), 127.50 (Ar C), 127.21
2
5
(
Ar C), 126.89 (Ar C), 126.66 (Ar C), 81.41, 35.12. [α]
(R)-1-(3′-Chlorophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)
ethanol (3c)
D
=
−42.6° (c 0.50 in CHCl ), colorless oil, retention times
3
(
min): 10.66 (S), 12.47 (R).
1
H NMR (400 MHz, CDCl ): δ=7.89–7.86 (m, 2H, Ar H),
3
7
.82 (s, 1H, Ar H), 7.80–7.72 (m, 2H, Ar H), 7.70–7.61
General method for the preparation of enantiopure
β‑hydroxytriazoles from α‑bromohydrins
(
m, 1H, Ar H), 7.51–7.48 (m, 1H, Ar H), 7.40–7.36 (m,
2
3
4
H, Ar H), 7.31–7.27 (m, 1H, Ar H), 5.41 (dd, J = 9.6,
.6 Hz, 1H, CH), 4.77 (dd, J = 12.0, 9.6 Hz, 1H, CH ),
2
In the second step, (32 mg, 0.5 mmol) sodium azide was
.71 (dd, J = 12.0, 3.6 Hz, 1H, CH ), 3.65 (br s, 1H, OH).
2
added to (0.5 mmol) chiral α-bromohydrins and water
1
3
C NMR (100 MHz, CDCl ): δ = 146.59 (C ), 140.78
3
q
(
10 mL) in 50 °C. The progress of the reaction was con-
(
(
C ), 135.51 (C ), 130.67 (C ), 130.14 (Ar C), 129.37
q q q
trolled by TLC. After completion of the reaction, termi-
nal acetylene (0.5 mmol), copper sulfate (0.13 mmol) and
sodium ascorbate (0.4 mmol) were added. The resulting
mixture was stirred at room temperature until complete
conversion of starting material, as indicated by TLC. After
extraction with ethyl acetate (3×30 mL), the organic phases
Ar C), 129.00 (Ar C), 128.45 (Ar C), 127.77 (Ar C),
1
6
1
27.23 (Ar C), 126.89 (Ar C), 122.63 (Ar C), 70.84 (CH),
2
5
2.93 (CH ). [α]
= − 40.8° (c 1.00 in CHCl ), mp:
3
2
D
20–123 °C, retention times (min): 27.0 (S), 29.1 (R).
were separated and dried over anhydrous MgSO , and the
4
(
R)-1-(4′-Chlorophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)
ethanol (4c)
solvent was removed under vacuum. The crude products
were purified by column chromatography on silica gel using
ethyl acetate/n-hexane gradient to give the desired product
in high purity.
1
H NMR (400 MHz, CDCl ): δ=8.12–8.10 (m, 2H, Ar H),
3
8
.05 (s, 1H, Ar H), 8.03–7.95 (m, 2H, Ar H), 7.94–7.61
(
m, 1H, Ar H), 7.53–7.50 (m, 2H, Ar H), 7.45–7.40 (m,
H, Ar H), 5.43 (dd, J = 8.0, 3.2 Hz, 1H, CH), 4.81 (dd,
(R)-1-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl) ethanol (1c)
2
J = 13.6, 8.0 Hz, 1H, CH ), 4.74 (dd, J = 13.6, 3.2 Hz, 1H,
2
1
H NMR (400 MHz, CDCl ): δ=8.05–8.03 (m, 2H, Ar H),
13
3
CH ), 3.69 (br s, 1H, OH). C NMR (100 MHz, CDCl ):
2
3
7
1
.97 (s, 1H, Ar H), 7.90–7.88 (m, 2H, Ar H), 7.72–7.68 (m,
H, Ar H), 7.59–7.55 (m, 2H, Ar H), 7.47–7.43 (m, 2H, Ar
δ = 149.30 (C ), 135.74 (C ), 133.73 (Ar C), 130.26 (C ),
q
q
q
1
29.58 (C ), 128.99 (Ar C), 128.62 (Ar C), 128.00 (Ar C),
q
H), 7.38–7.34 (m, 1H, Ar H), 5.36 (dd, J=8.8, 2.4 Hz, 1H,
1
27.97 (Ar C), 121.28 (Ar C), 69.00 (CH), 63.30 (CH ).
2
CH), 4.74 (dd, J=11.6, 8.8 Hz, 1H, CH ), 4.68 (dd, J=11.6,
25
2
[α]
= − 48.2° (c 1.00 in CHCl ) [lit. +48.93° (c 1.00
D
3
13
2
.4 Hz, 1H, CH ), 3.62 (br s, 1H, OH). C NMR (100 MHz,
2
in acetone), for S isomer] [7], mp: 218 °C, retention times
CDCl ): δ=148.22 (C ), 136.65 (C ), 135.95 (Ar C), 130.01
3
q
q
(min): 30.4 (S), 33.8 (R).
(
(
(
C ), 129.76 (Ar C), 128.84 (Ar C), 128.22 (Ar C), 128.20
q
Ar C), 125.83 (Ar C), 121.50 (Ar C), 74.23 (CH), 65.10
25
CH ). [α] = −38.6° (c 1.50 in CHCl ), mp: 114–116 °C,
2
D
3
(R)-1-(4′-Methoxyphenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)
ethanol (5c)
retention times (min): 24.4 (S), 28.7 (R).
1
(
R)-1-(4′-Bromophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)
H NMR (400 MHz, CDCl ): δ=7.74–7.72 (m, 2H, Ar H),
3
ethanol (2c)
7.67 (s, 1H, Ar H), 7.65–7.57 (m, 2H, Ar H), 7.56–7.33
(
m, 1H, Ar H), 7.25–7.22 (m, 2H, Ar H), 7.17–7.13 (m,
1
H NMR (400 MHz, CDCl ): δ=8.07–8.05 (m, 2H, Ar H),
2H, Ar H), 5.25 (dd, J = 9.2, 2.8 Hz, 1H, CH), 4.63 (dd,
3
7
.99 (s, 1H, Ar H), 7.91–7.89 (m, 2H, Ar H), 7.74–7.70
J = 11.6, 9.2 Hz, 1H, CH ), 4.57 (dd, J = 11.6, 2.8 Hz, 1H,
2
1
3
(
m, 1H, Ar H), 7.60–7.57 (m, 2H, Ar H), 7.49–7.36 (m,
H, Ar H), 5.38 (dd, J = 8.4, 4.0 Hz, 1H, CH), 4.76 (dd,
J = 12.4, 8.4 Hz, 1H, CH ), 4.70 (dd, J = 12.4, 4.0 Hz, 1H,
CH ), 4.50 (s, 3H, CH ), 3.54 (br s, 1H, OH). C NMR
2
3
2
(100 MHz, CDCl ): δ = 147.90 (C ), 141.52 (C ), 136.33
3 q q
(Ar C), 133.63 (C ), 129.43 (C ), 128.79 (Ar C), 128.42
2
q
q
1
3
CH ), 3.64 (br s, 1H, OH). C NMR (100 MHz, CDCl );
(Ar C), 127.77 (Ar C), 125.92 (Ar C), 121.18 (Ar C),
2
3
2
5
δ = 148.20 (C ), 136.63 (C ), 134.93 (Ar C), 129.73 (Ar
68.90 (CH), 63.20 (CH ), 57.78 (CH ). [α]
= − 42.5°
q
q
2
3
D
C), 129.19 (C ), 128.20 (Ar C), 128.17 (Ar C), 128.03 (Ar
(c 1.00 in CHCl ), mp: 149–152 °C, retention times (min):
q
3
C), 126.22 (Ar C), 121.48 (C ), 68.69 (CH), 62.99 (CH ).
29.5 (S), 34.3 (R).
q
2
1
3

Journal of the Iranian Chemical Society
(
(
R)-1-Naphtyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl) ethanol
6c)
(R)-1-Phenyl-2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl) ethanol
(9c)
1
1
H NMR (400 MHz, CDCl ): δ=8.03–8.02 (m, 2H, Ar H),
H NMR (400 MHz, CDCl ): δ=8.09–8.07 (m, 2H, Ar H),
3
3
8
.01 (s, 1H, Ar H), 7.95–7.87 (m, 2H, Ar H), 7.86–7.69
7.99 (s, 1H, Ar H), 7.92–7.74 (m, 2H, Ar H), 7.73–7.70
(
m, 1H, Ar H), 7.68–7.66 (m, 1H, Ar H), 7.57–7.53 (m,
(m, 1H, Ar H), 5.56 (dd, J=9.6, 4.0 Hz, 1H, CH), 4.78 (t,
1
H, Ar H), 7.45–7.41 (m, 2H, Ar H), 7.36–7.34 (m, 2H, Ar
J=1.6 Hz, 2H, CH), 4.44 (dd, J=14.0, 9.6 Hz, 1H, CH ),
2
H), 7.33–7.26 (m, 1H, Ar H), 5.40 (dd, J=9.6, 3.6 Hz, 1H,
4.38 (dd, J = 14.0, 4.0 Hz, 1H, CH ), 4.20 (t, J = 1.6 Hz,
2
1
3
CH), 4.77 (dd, J=12.0, 9.6 Hz, 1H, CH ), 4.70 (dd, J=12.0,
2H, CH), 4.06 (s, 5H, CH), 3.41 (br s, 1H, OH). C NMR
2
13
3
.6 Hz, 1H, CH ), 3.65 (br s, 1H, OH). C NMR (100 MHz,
(100 MHz, CDCl ): δ=147.29 (C ), 133.64 (C ), 132.16 (Ar
2
3
q
q
CDCl ): δ=146.59 (C ), 140.78 (C ), 133.51 (C ), 131.14
C), 129.47 (Ar C), 122.85 (C ), 119.01 (Ar C), 76.65 (CH),
3
q
q
q
q
(
Ar C), 130.67 (C ), 129.37 (C ), 129.00 (Ar C), 128.80 (Ar
72.32 (CH), 68.68 (CH), 67.97 (CH), 66.75 (CH), 64.22
q
q
C), 128.54 (Ar C), 127.77 (Ar C), 127.46 (Ar C), 127.23
(CH ). Anal. Calcd. for C H N OFe (373.27): C, 64.35;
2
20 19
3
(
Ar C), 126.79 (Ar C), 126.41 (Ar C), 125.66 (Ar C), 121.39
H, 5.12; N, 11.25; O, 4.28; Fe, 14.96. Found: C, 64.20; H,
2
5
25
(
Ar C), 72.43 (CH), 60.87 (CH ). [α]
= −45.3° (c 1.00
5.32; N, 11.14. [α]
= − 59.9° (c 1.00 in CHCl ), mp:
3
2
D
D
in CHCl ), mp: 230–232 °C, retention times (min): 25.5 (S),
224–226 °C, retention times (min): 11.4 (S), 14.9 (R).
3
2
9.9 (R).
General procedure for the synthesis of chiral styrene
oxides
(
R)-1-Phenyl-2-(4-(1-hydroxycyclohexyl)-1H-1,2,3-tria-
zol-1-yl) ethanol (7c)
For the preparation of chiral styrene oxides, 3 mL NaOH
(2 N) was added to α-bromohydrin (0.5 mmol) in 6 mL tet-
rahydrofuran (THF) and then was sttired at room tempera-
ture for 1 h. After completing the reaction, the product was
extracted by EtOAc and then purified using column chroma-
tography on silica gel using ethyl acetate/n-hexane gradient
to give the desired product in high purity.
1
H NMR (400 MHz, CDCl ): δ=7.94–7.92 (m, 2H, Ar H).
3
7
1
.86 (s, 1H, Ar H), 7.79–7.77 (m, 2H, Ar H), 7.61–7.57 (m,
H, Ar H), 5.24 (dd, J = 9.6, 2.4 Hz, 1H, CH), 4.40 (dd,
J=12.0, 9.6 Hz, 1H, CH ), 4.37 (dd, J=12.0, 2.4 Hz, 1H,
2
CH ), 3.55 (br s, 1H, OH), 3.79 (s, 1H, OH), 1.95–1.80 (m,
2
2
H, CH ), 1.71–1.59 (m, 4H, CH ), 1.49–1.36 (m, 3H, CH ),
2
2
2
1
3
1
.30–1.21 (m, 1H, CH ). C NMR (100 MHz, CDCl ):
2
3
δ=147.54 (C ), 136.02 (C ), 133.46 (Ar C), 130.31 (Ar C),
q
q
1
29.14 (Ar C), 126.00 (Ar C), 73.77 (C ), 64.19 (CH), 60.99
(R)-Phenyl oxiran (1d)
q
(
CH ), 36.12 (CH ), 24.24 (CH ), 22.70 (CH ). Anal. Calcd.
2 2 2 2
1
for C H N O (287.39): C, 66.86; H, 7.36; N, 14.62; O,
H NMR (400 MHz, CDCl ): δ=7.41–7.27 (m, 5H, Ar H),
1
6
21
3
2
3
2
5
1
1.13. Found: C, 66.60; H, 7.21; N, 14.73. [α] = −11.7°
3.70 (dd, J=2.8, 2.6 Hz, 1H, CH), 2.81 (dd, J=5.6, 2.8 Hz,
D
1
3
(
c 1.00 in CHCl ), mp: 227–231 °C, retention times (min):
1H, CH ), 2.53 (dd, J = 5.6, 2.6 Hz, 1H, CH ). C NMR
3
2
2
1
0.7 (S), 13.7 (R).
(100 MHz, CDCl ): δ=137.04 (C ), 130.05 (Ar C), 130.00
3
q
2
5
(
Ar C), 129.75 (Ar C), 57.10 (CH), 51.44 (CH ). [α]
=
2
D
2
0
−
27.0° (c 1.0 in CHCl ), Lit.[α] = + 25.1° (c 1.10 in
3 D
(
R)-1-Phenyl-2-(4-(2-hydroxypropane-2-yl)-1H-1,2,3-tria-
CHCl , for S enantiomer) [48], colorless oil, retention times
3
zol-1-yl) ethanol (8c)
(min): 40.8 (S), 45.2 (R).
1
H NMR (400 MHz, CDCl ): δ=8.09–8.07 (m, 2H, Ar H),
3
7
1
.99 (s, 1H, Ar H), 7.92–7.90 (m, 2H, Ar H), 7.74–7.70 (m,
(R)-4-Bromo-phenyl oxiran (2d)
H, Ar H), 5.26 (dd, J = 8.0, 2.4 Hz, 1H, CH), 4.62 (dd,
1
J=11.2, 8.0 Hz, 1H, CH ), 4.57 (dd, J=11.2, 2.4 Hz, 1H,
H NMR (400 MHz, CDCl ); δ=δ(ppm): 7.68–7.63 (m, 2H,
2
3
CH ), 4.20 (s, 1H, OH), 3.49 (br s, 1H, OH), 1.90 (s, 6H,
Ar H), 7.41–7.38 (m, 2H, Ar H), 3.71 (dd, J=4.0, 2.4 Hz,
2
13
CH ). C NMR (100 MHz, CDCl ): δ=146.96 (C ), 136.13
1H, CH), 2.81 (dd, J = 7.6, 4.0 Hz, 1H, CH ), 2.52 (dd,
3
3
q
2
1
3
(
(
C ), 134.73 (Ar C), 129.09 (Ar C), 128.28 (Ar C), 126.88
J = 7.6, 2.4 Hz, 1H, CH ). C NMR (100 MHz, CDCl ):
q
2
3
Ar C), 74.23 (C ), 65.10 (CH), 51.17 (CH ), 30.45 (CH ).
δ=136.70 (C ), 131.66 (Ar C), 127.23 (Ar C), 122.88 (C ),
q
2
3
q
q
25
Anal. Calcd. for C H N O (247.31): C, 63.13; H, 6.92; N,
56.60 (CH), 50.12 (CH ). [α] = −13.7° (c 1.5 in CHCl );
2 D 3
1
3
17
3
2
2
5
20
1
7.00; O, 12.94. Found: C, 63.02; H, 7.00; N, 17.13. [α]
Lit.[α] = + 13.6° (c = 1.46 in CHCl for S enantiomer)
D 3
D
=
− 22.6° (c 0.50 in CHCl ), mp: 192–194 °C, retention
[49], colorless oil, retention times (min): 35.03 (S), 40.72
(R).
3
times (min): 16.6 (S), 19.3 (R).
1
3

Journal of the Iranian Chemical Society
(
R)-3-Chloro-phenyl oxiran (3d)
O
O
O
O
Br
Br
Br
Br
1
H NMR (400 MHz, CDCl ); δ=7.59–7.50 (m, 1H, Ar H),
3
Br
7
.46–7.41 (m, 2H, Ar H), 7.38–7.33 (m, 1H, Ar H), 3.62
Cl
(
(
dd, J = 3.2, 2.8 Hz, 1H, CH), 2.72 (dd, J = 5.6, 3.2 Hz,
(1)
(2)
3)
1
3
1
H, CH ), 2.43 (dd, J = 5.6, 2.8 Hz, 1H, CH ). C NMR
2
2
O
O
(
(
(
[
100 MHz, CDCl ): δ=139.96 (C ), 135.02 (Ar C), 129.67
Br
3
q
Br
Ar C), 129.11 (C ), 127.13 (Ar C), 126.99 (Ar C), 57.10
q
2
5
CH), 51.68 (CH ). [α]
= − 11° (c 1.8 in CHCl ), Lit.
3
Cl
H
3
CO
2
D
3
25
α] =+9° (c 1.20 in CHCl for S enantiomer) [49], color-
D
(4)
(5)
(6)
less oil, retention times (min): 44.1 (S), 48.3 (R).
Fig. 1 α-Bromoketones studied in the bioreduction
(R)-4-Chloro-phenyl oxiran (4d)
1
H NMR (400 MHz, CDCl ): δ = 7.49–7.45 (m, 2H, Ar
Table 1 Bioreduction of α-bromoketones to chiral α-bromohydrins
with Daucus carota
3
H), 7.23–7.20 (m, 2H, Ar H), 3.60 (dd, J=3.2, 2.8 Hz, 1H,
CH), 2.71 (dd, J=6.4, 2.8 Hz, 1H, CH ), 2.42 (dd, J=6.4,
2
OH
1
3
O
3
.2 Hz, 1H, CH ). C NMR (100 MHz, CDCl ): δ=136.56
2
3
Br
Br
(
(
[
C ), 133.42 (C ), 130.01 (Ar C), 128.46 (Ar C), 57.01
Daucus Carota
q
q
2
5
CH), 50.94 (CH ). [α] = −21.1° (c 1.2 in CHCl ); Lit.
2
D
3
H O, r.t
2
2
0
R
R
α] =+19.3° (c=1.16 in CHCl , for S enantiomer) [49],
D
3
colorless oil, retention times (min): 42.5 (S), 46.2 (R).
1
a-6a
1
-6
(R)-4-Methoxy-phenyl oxiran (5d)
Entry
Product
Time (h)
Isolated yield ee (%)b
1
H NMR (400 MHz, CDCl ): δ = 7.49–7.44 (m, 2H, Ar
(%)a
3
H), 7.22–7.20 (m, 2H, Ar H), 3.90 (s, 3H, CH3), 3.60 (dd,
1
2
3
4
5
6
1a
2a
3a
4a
5a
6a
48
30
40
32
35
40
65
90
75
90
50
70
82 (R)
95 (R)
85 (R)
87 (R)
91 (R)
80 (R)
J=4.4, 3.6 Hz, 1H, CH), 2.70 (dd, J=6.8, 4.4 Hz, 1H, CH ),
2
1
3
2
.42 (dd, J=6.8, 3.6 Hz, 1H, CH ). C NMR (100 MHz,
2
CDCl ): δ=157.96 (C ), 130.00 (C ), 127.50 (Ar C), 113.72
3
q
q
2
5
(
Ar C), 57.25 (CH ), 56.67 (CH), 51.01 (CH ). [α]
=
3
2
D
−
31.4° (c 1.00 in CHCl ), colorless oil, retention times
3
(
min): 39.0 (S), 41.9 (R).
Reaction condition: α-bromoketones (1.0 mmol), D. carota roots
(
R)-Naphtyl oxiran (6d)
(17 g), distilled water (100 mL), at 30 °C
a
Isolated yield after column chromatography
Determined by HPLC
1
b
H NMR (400 MHz, CDCl ): δ = 7.92 (d, J = 9.6 Hz, 1H,
3
Ar H), 7.89–7.78 (m, 3H, Ar H), 7.77–7.58 (m, 3H, Ar H),
4
1
.07 (dd, J=3.2, 2.8 Hz, 1H, CH), 2.73 (dd, J=5.6, 3.2 Hz,
13
H, CH ), 2.44 (dd, J= 5.6, 2.8 Hz, 1H, CH ). C NMR:
biocatalyst for the asymmetric reduction of phenacyl bro-
mide derivatives to optically active alcohols due to its opera-
tional simplicity, the easy isolation of the reaction products,
the inexpensive and readily available biomaterial, the mild
conditions and the high yield and enantioselectivity.
2
2
(
(
(
(
100 MHz, CDCl ): δ = 139.73 (C ), 133.35 (C ), 130.05
3 q q
C ), 128.59 (Ar C), 127.41 (Ar C), 126.89 (Ar C), 125.26
q
Ar C), 124.57 (Ar C), 122.89 (Ar C), 122.00 (Ar C), 58.21
2
5
CH), 51.33 (CH ). [α]
= − 23.9° (c 1.00 in CHCl ),
3
2
D
colorless oil, retention times (min): 35.7 (S), 37.2 (R).
The results of the stereoselective reduction of phenacyl
bromides 1–6 with D. carota are summarized in Table 1. The
corresponding chiral halohydrins (1a–6a) with R configura-
tion were formed in high yields with excellent enantiomeric
excess. The enantiomeric excess of these alcohols was deter-
mined by chiral HPLC analysis. The observed stereochem-
istry could be explained on the basis of Prelog’s rule [50]
and the absolute configuration was simply determined by
measuring their specific rotations. All of the chiral alcohols
Results and discussion
In the first step of our present strategy, we have investigated
the bioreduction of α-bromoketones (1–6, shown in Fig. 1)
bearing aromatic (phenyl or 2-naphthyl) groups with bromo,
chloro or methoxy substituents. We chose D. carota as the
1
3

Journal of the Iranian Chemical Society
have been prepared previously as single enantiomers and the
absolute configurations were assigned by comparison of the
optical rotation data measured with values reported in the
literature [13, 39, 44, 47].
cyclic intermediate 2 which finally transformed to 1,2,3-tria-
zole and regenerates the copper catalyst for further reactions
(Scheme 2).
The results for S 2 reaction and its sequential cycloaddi-
N
The asymmetric bioreduction of phenacyl bromides was
accomplished by a suspension of freshly sliced D. carota
roots in water at 30 °C for 30–48 h. As shown in Table 1,
the phenacyl bromide (1) was converted to its corresponding
alcohol in 65% yield with 82% ee. To examine the scope and
limitations of the protocol, substituted phenacyl bromides
possessing electron-donating and electron-withdrawing
groups were reduced under the reaction conditions. The best
results were achieved with phenacyl bromides with electron-
withdrawing groups Cl and Br in para-position of phenyl
ring (Table 1, entries 2 and 4). Even though para-methoxy
phenacyl bromide gave moderate yield of the corresponding
halohydrin but with high ee (Table 1, entry 5). In addition,
the bioreduction of ketones with meta-choloro phenyl and
tion with alkynes are summarized in Table 2.
As shown in Table 2, the present protocol was very effec-
tive for the synthesis of β-hydroxy 1,2,3-triazoles. Reaction
of phenyl acetylene with 2-azido-1-arylethanoles gave excel-
lent yields of the corresponding chiral triazoles in high enan-
tiomeric excess for most cases (Table 2, entries 1–6). A simi-
lar trend was also observed for propargyl alcohols (Table 2,
entries 7 and 8) and ferrocene acetylene (Table 2, entry 9).
Homochiral styrene oxides are key intermediates for the
synthesis of chiral ligands, natural products and chiral drugs
in enantiopure form. (R)-2-bromo-1-arylethanols prepared
from the reduction of the phenacyl bromides by carrot root
were applied for the synthesis of chiral styrene oxides. The
S 2 ring-closure of 2-bromo-1-arylethanols by treatment
N
2
-naphthyl groups were also proceeded smoothly and gave
good yields of the desired products (Table 1, entries 3 and
).
with 2N NaOH in THF for 1 h afforded the corresponding
epoxides in high yields and excellent enantiomeric excess.
The reaction is an intramolecular variation of the Wil-
liamson ether synthesis. The alkoxide anion, formed revers-
ibly by the reaction of bromohydrin with NaOH, displaces
bromide ion from the neighboring carbon to afford the
desired epoxide (Scheme 3).
6
As mentioned in “Introduction” section, chiral
α-halohydrins are important intermediates for the synthe-
sis of enantiopure β-Hydroxy 1,2,3-triazoles and also chiral
epoxides. The preparation of β-hydroxy 1,2,3-triazoles was
achieved in a straightforward procedure simply by S 2 reac-
The results are summarized in Table 3. The best results
were achieved when (R)-2-bromo-1-(4′-bromophenyl) etha-
nol (2a) and (R)-2-bromo-1-(4′-chlorophenyl) ethanol (4a)
were transformed to the corresponding epoxides under basic
conditions (Table 3, entries 2 and 4).
N
tion of 2-bromo-1-arylethanols with sodium azide in water
followed by click reaction with terminal alkynes in the pres-
ence of copper catalyst (Scheme 1).
Azido compounds are often unstable to heat and light;
therefore, in situ formation of these compounds is advanta-
geous to handle them safely. The S 2 reaction was com-
N
pleted at 50 °C in less than 30 min as monitored by TLC
and 2-azidio-1-arylethanols were formed almost quantita-
tively. The in situ-generated azido alcohols were then reacted
with different terminal alkynes using copper sulfate and
sodium ascorbate to give the corresponding β-hydroxy-1,4-
disubstituted-1,2,3-triazoles in high yields. The copper-cat-
alyzed azide-alkyne cycloaddition (CuAAC) is well estab-
lished and its mechanism was reported [51–53]. Based on
the results reported in the literature, it can be assumed that
the copper (I) initially forms an acetylide with the terminal
alkyne which reacts with azido compounds. Then intramo-
lecular cyclization of resulting intermediates 1 produces the
Conclusion
In summary, a useful procedure for the synthesis of chiral
β-hydroxy 1,2,3-triazoles and chiral styrene oxides from
α- bromoketones has been reported. The procedure con-
sists of the use of cheap and readily available reagents,
water as solvent and carrot bits as biocatalysts. Intact cells
from cut portions of D. carota root mediated efficiently the
asymmetric reduction of α-bromoketones. The resulting
optically active alcohols are the potential chiral building
blocks for the synthesis of biologically important mole-
cules. The preparation of optical active β-hydroxytriazoles
Scheme 1 The conversion
OH
OH
CuSO4
of 2-bromo-1-arylethanols to
N
OH
N
N
β-Hydroxy 1,2,3-triazoles
Br
Water, 50 C
N3
sodium ascorbate
NaN3
R2
R1
o
R2
R
R
1
c-9c
1
a-6a
1b-6b
1
3

Journal of the Iranian Chemical Society
R1
Scheme 2 Proposed mechanism
of the formation of β-hydroxy-
CuLn-1
OH
1
,2,3-triazole
N
N
R1
R2
N
CuLn-2 OH
N
3
N
N
R2
2
R1
OH
N
N
R2
N
R1
CuL
n-2 OH
+
N
-
N
R2
[LnCu]+
N
1
R1
H
R1
CuLn-1
OH
OH
N
+
-
NaN3 Br
N
N
R2
R2
Table 2 The synthesis of
ee (%)c
Entry
R1
Phenyl
p-Bromophenyl
m-Chlorophenyl
p-Chlorophenyl
p-Methoxyphenyl
2-Naphtyl
Phenyl
R2
Products
Time (min)
Isolated
β-hydroxy 1,2,3-triazoles from
b
yield (%)
2
-bromo-1-arylethanols and
terminal alkynes through click
1
2
3
4
5
6
7
8
9
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
CH(OH)(CH2)5
(CH ) CHOH
Ferrocenyl
1c
2c
3c
4c
5c
6c
7c
8c
9c
55
45
50
40
40
55
60
60
45
90
98
97
98
91
90
90
95
93
75 (R)
97 (R)
87 (R)
90 (R)
90 (R)
90 (R)
83 (R)
79 (R)
80 (R)
a
reaction
N
OH
N
N
R2
R1
Phenyl
Phenyl
3
2
Reaction condition: chiral α-bromohydrins (0.5 mmol), sodium azide (0.5 mmol), water (10 mL), in 50 °C
in second step, terminal acetylene (0.5 mmol), copper sulfate (32 mg) and sodium ascorbate (80 mg)
a
Yield of isolated product
Determined by HPLC
b
and chiral styrene oxides are two examples and further
OH-
H O
2
studies are in progress to obtain other important chiral
compounds.
H
O-
O
O
Br
Br
R
R
R
Scheme 3 Proposed mechanism for the synthesis of chiral styrene
oxide
1
3

Journal of the Iranian Chemical Society
Table 3 The conversion of 2-bromo-1-arylethanols to styrene oxides
10. G. Kumaraswamy, K. Ankamma, A. Pitchaiah, J. Org. Chem.
7
2, 9822 (2007)
1
1
1. J.H. Schrittwieser, F. Coccia, S. Kara, B. Grischek, W. Kroutil,
N. D’Alessandro, F. Hollmann, Green Chem. 15, 3318 (2013)
2. W. Szymanski, C.P. Postema, C. Tarabiono, F. Berthiol, L.
Campbell-Verduyn, S. de Wildeman, D.B. Janssen, Adv. Synth.
Catal. 352, 2111 (2010)
OH
O
Br
NaOH (2N)
THF, r.t, 1h
R
R
13. M. Fallah-Mehrjardi, A.R. Kiasat, K. Niknam, J. Iran. Chem.
Soc. 15, 2033 (2018)
1
a-6a
1
d-6d
1
1
4. C. Barbieri, L. Bossi, P. D’Arrigo, G.P. Fantoni, S. Servi, J. Mol.
Catal. B Enzym. 11, 415 (2001)
5. S. Pedragosa-Moreau, C. Morisseau, J. Baratti, J. Zylber, A.
Archelas, R. Furstoss, Tetrahedron 53, 9707 (1997)
Entry
Product
R
Isolated yield ee (%)b
1
1
6. T. Katsuki, K.B. Sharpless, J. Am. Chem. Soc. 102, 5974 (1980)
7. S.A. Weissman, K. Rossen, P.J. Reider, Org. Lett. 3, 2513
a
(
%)
(
2001)
1
2
3
4
5
6
1d
2d
3d
4d
5d
6d
H
95
98
90
98
95
92
83 (R)
97 (R)
86 (R)
99 (R)
93 (R)
85 (R)
1
8. M. Palucki, G.J. McCormick, E.N. Jacobsen, Tetrahedron lett
p-Br
m-Cl
p-Cl
3
6, 5457 (1995)
19. M. Palucki, P.J. Pospisil, W. Zhang, E.N. Jacobsen, J. Am.
Chem. Soc. 116, 9333 (1994)
2
2
0. B.D. Brandes, E.N. Jacobsen, Tetrahedron Asymmetry 8, 3927
p-OCH
3
(
1997)
c
–
1. M. Tokunaga, J.F. Larrow, F. Kakiuchi, E.N. Jacobsen, Science
2
77, 936 (1997)
Reaction condition: chiral α-bromohydrins (0.5 mmol), NaOH (2 N,
2
2
2. I.M. Pastor, M. Yus, Curr. Org. Chem. 9, 1 (2005)
3. A. Magnus, S.K. Bertilsson, P.G. Andersson, Chem. Soc. Rev.
31, 223 (2002)
3
mL), THF (6 mL), at room temperature
a
Yield of isolated product
Determined by HPLC
b
c
24. F. Yu, J.N. Zhou, X.C. Zhang, Y.Z. Sui, F.F. Wu, L.J. Xie, J.
Wu, Chem. Eur. J. 17, 14234 (2011)
2
-Bromo-1-naphtylethanol was used
2
5. S. Eagon, N. Ball-Jones, D. Haddenham, J. Saavedra, C.
DeLieto, M. Buckman, B. Singaram, Tetrahedron Lett. 51, 6418
(
2010)
Acknowledgements Financial support of this work from the Research
2
2
2
6. F. Martínez, C. Del Campo, J.V. Sinisterra, E.F. Llama, Tetra-
hedron Asymmetry 11, 4651 (2000)
Council of University of Mazandaran is gratefully acknowledged.
7. Y. Yasohara, N. Kizaki, J. Hasegawa, M. Wada, M. Kataoka, S.
Shimizu, Tetrahedron Asymmetry 12, 1713 (2001)
8. E. Sahin, Biocatal. Biotransformation 35, 363 (2017)
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
29. E. Sahin, Chirality 30, 189 (2018)
interest.
30. E. Sahin, E. Dertli, Chem. Biodivers. 14, e1700121 (2017)
3
3
3
1. D. Yilmaz, E. Sahin, E. Dertli, Chem. Biodivers. 14, e1700269
(
2017)
2. N.A. Salvi, S. Chattopadhyay, Tetrahedron Asymmetry 27, 188
References
(
2016)
3. X. Chang, Y.A.N.G. Zhonghua, Z.E.N.G. Rong, Y.A.N.G. Gai,
1
.
W.Q. Fan, A.R. Katritzky, In Comprehensive Heterocyclic
Chemistry II, ed. by A.R. Katritzky, C.W. Rees, E.F.V. Scriven
Y.A.N. Jiabao, Chin. J. Chem. Eng. 18, 1029 (2010)
34. N. Blanchard, P. van de Weghe, Org. Biomol. Chem. 4, 2348
(2006)
(
Elsevier Science, Oxford, 1996), pp. 1–126
2
.
S. Velazquez, R. Alvarez, C. Perez, F. Gago, E. De Clercq, J.
35. K. Ishihara, H. Hamada, T. Hirata, N. Nakajima, J. Mol. Catal.
B Enzym. 23, 145 (2003)
Balzarini, M.J. Camarasa, Antivir. Chem. Chemother. 9, 481
(
1998)
36. J.S. Yadav, S. Nanda, P.T. Reddy, A.B. Rao, J. Org. Chem. 67,
3900 (2002)
3
4
5
6
7
8
9
.
.
.
.
.
.
.
J. Capilla, M. Ortoneda, F.J. Pastor, J. Guarro, Antimicrob.
Agents Chemother. 45, 2635 (2001)
37. W.K. Mączka, A. Mironowicz, Tetrahedron Asymmetry 13,
2299 (2002)
K. Colanceska-Ragenovic, V. Dimova, V. Kakurinov, D.G. Mol-
nar, A. Buzarovska, Molecules 6, 815 (2001)
38. F. Baldassarre, G. Bertoni, C. Chiappe, F. Marioni, J. Mol.
Catal. B Enzym. 11, 55 (2000)
A. Jarrahpour, M. Aye, J.A. Rad, S. Yousefinejad, V. Sinou, C.
Latour, E. Turos, J. Iran. Chem. Soc. 15, 1311 (2018)
H. Ankati, Y. Yang, D. Zhu, E.R. Biehl, L. Hua, J. Org. Chem.
39. J.S. Yadav, P.T. Reddy, S. Nanda, A.B. Rao, Tetrahedron Asym-
metry 12, 3381 (2002)
7
3, 6433 (2008)
40. M. Mohadjerani, R. Hosseinzadeh, S. Mesgar, Clin. Biochem.
44, S87 (2011)
M.J. Giffin, H. Heaslet, A. Brik, Y.C. Lin, G. Cauvi, C.H. Wong,
B.E. Torbett, J. Med. Chem. 51, 6263 (2008)
41. S. Mesgar, Enantioselective reduction of nonsymmetric ketones
using biocatalysts such as carrot root. M.Sc. Thesis, University
of Mazandaran (2012)
A. Brik, J. Alexandratos, Y.C. Lin, J.H. Elder, A.J. Olson, A.
Wlodawer, C.H. Wong, Chem. Biol. Chem. 6, 1167 (2005)
L.S. Campbell-Verduyn, W. Szymański, C.P. Postema, R.A.
Dierckx, P.H. Elsinga, D.B. Janssen, B.L. Feringa, Chem. Com-
mun. 46, 898 (2010)
42. F. Darvishi, Bioreduction of organic compounds such as alde-
hydes by Dacus carota root as biocatalyst. M.Sc. Thesis, Uni-
versity of Mazandaran (2014)
1
3

Journal of the Iranian Chemical Society
4
4
4
4
4
4
3. A.I. Vogel, Practical organic chemistry, 3rd edn., (Longmans
Group Limited, New York, 1978), p. 815
49. S. Pedragosa-Moreau, C. Morisseau, J. Zylber, A. Archelas, J.
Baratti, R. Furstoss, J. Org. Chem. 61, 7402 (1996)
50. V. Prelog, Pure Appl. Chem. 9, 119 (1964)
4. D. Basavaiah, K.V. Rao, B.S. Reddy, Tetrahedron Asymmetry
1
7, 1041 (2006)
51. D. Kumar, V.B. Reddy, R.S. Varma, Tetrahedron Lett. 50, 2065
(2009)
5. H. Lin, Y.Z. Chen, X.Y. Xu, S.W. Xia, L.X. Wang, J. Mol. Catal.
B Enzym. 57, 1–5 (2009)
52. H. Sharghi, M.H. Beyzavi, A. Safavi, M.M. Doroodmand, R.
Khalifeh, Adv. Synth. Catal. 351, 2391 (2009)
6. D. Basavaiah, G.J. Reddy, V. Chandrashekar, Tetrahedron
Asymmetry 15, 47 (2004)
53. F. Himo, T. Lovell, R. Hilgraf, V.V. Rostovtsev, L. Noodleman,
K.B. Sharpless, V.V. Fokin, J. Am. Chem. Soc. 127, 210 (2005)
7. K. Kaur, S.S. Chimni, H.S. Saini, B.S. Chadha, Biocatal. Agric.
Biotechnol. 4, 49 (2015)
8. F. Wang, H. Liu, L. Cun, J. Zhu, J. Deng, Y. Jiang, J. Org.
Chem. 70, 9424 (2005)
1
3