Enantioselective oxidation of secondary alcohols by Candida parapsilosis ATCC 7330

Article abstract of DOI:10.1039/c3ra46206d

Optically pure allylic alcohols and 4-phenylbutan-2-ols were prepared by oxidative kinetic resolution using whole cells of Candida parapsilosis ATCC 7330. Only the 'S' enantiomer is selectively oxidized to the corresponding keto compound (yield, 37-46%) leaving the 'R' alcohol (yield, 37-52% and ee 46 to >99%). The biocatalytic method is carried out under mild conditions at 20°C, pH 6.5 in phosphate buffer.

Full text of DOI:10.1039/c3ra46206d

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Enantioselective oxidation of secondary alcohols
by Candida parapsilosis ATCC 7330
Cite this: RSC Adv., 2014, 4, 2257
ac
Thakkellapati Sivakumari,a Radhakrishnan Preethaab and Anju Chadha
*
Received 29th October 2013
Accepted 20th November 2013
DOI: 10.1039/c3ra46206d
www.rsc.org/advances
Optically pure allylic alcohols and 4-phenylbutan-2-ols were prepared methods for cofactor regeneration.20 But, as more progress has
by oxidative kinetic resolution using whole cells of Candida para- been made for cofactor regeneration by using various strategies
psilosis ATCC 7330. Only the ‘S’ enantiomer is selectively oxidized to viz substrate coupled approach,21 enzyme coupled approach
the corresponding keto compound (yield, 37–46%) leaving the ‘R’ using oxidases,22 alcohol dehydrogenases,23 chemical regener-
alcohol (yield, 37–52% and ee 46 to >99%). The biocatalytic method is ation,23 photochemical regeneration23 and electrochemical
carried out under mild conditions at 20 ꢀC, pH 6.5 in phosphate buffer. regeneration24 there is a renewed interest in developing bio-
catalyst mediated oxidation methods.
Preparation of optically pure secondary alcohols is reported
Introduction
by deracemization,25 asymmetric reduction26 and oxidative
kinetic resolution21,27–29 using biocatalysts. Cyclic and alicyclic
racemic secondary alcohols were resolved via oxidative kinetic
resolution using Yarrowia lipolytica strains.30 Lyophilised
Rhodococcus ruber DSM 44541 cells were used for the oxidative
kinetic resolution of saturated and unsaturated 2-butanol and
2-pentanols.31 Enantioselective oxidation of methyl arylmetha-
nols by whole cells of Nocardia corallina B-276 is known.32
Oxidative kinetic resolution of substituted phenyl ethanols,
heterocyclic secondary alcohols and cyclic secondary alcohols
was reported by a galactose oxidase variant.33 Raspberry ketone
which has a wide range of industrial applications was also
obtained by oxidative kinetic resolution using R. ruber DSM
44541.27 Enantio-, and regioselective oxidation of sec-alcohols
employing alcohol dehydrogenase ADH-‘A’ in the wild type
strain as well as over-expressed in E. coli is reported.34 Similarly,
(R)- and (S)-1-phenylethanol derivatives were prepared by plant
cell biocatalysts.28
Alcohol oxidation is a fundamental step in synthetic organic
chemistry as the resulting carbonyl compounds are used as
either precursors or intermediates in the synthesis of several
bioactive compounds.1 Metal based oxidizing agents2 (Cr, Mn,
Fe and Al) and non metallic chemical oxidizing reagents such as
activated DMSO, Iodine, TEMPO3 are reported so far. In an
effort to reduce metal wastes, ligands that can be used in
catalytic amounts are also reported, for example, ligands of Ru,
Pd, and Cu.4 Chemical oxidation methods oen result in over-
oxidation and formation of side products.5 Thus, there is a
constant need to develop oxidation methods which are efficient
and environmentally benign.
Developing bio catalytic oxidation methods are an effort in
this direction. Biocatalysts are desirable due to their selectivity,
specicity and mild reaction conditions.6,7 Whole cells (bacte-
rial, fungal and plant cells)8,9 and isolated enzymes10–16 are
reported for the oxidation of alcohols. Unlike puried enzymes
which require external addition of cofactors for oxidation and
reduction reactions, whole cells do not require additional
cofactors and therefore can serve as better biocatalysts.17–19
Enzyme mediated oxidation of alcohols is less frequently
documented in literature due to lack of efficient recycling
Studies from our laboratory have established Candida para-
psilosis ATCC 7330 as an efficient biocatalyst for deracemization
of a, b-hydroxy esters,35–38 asymmetric reduction of a, b-keto
esters,39,40 imines,41 a-keto amides,42 oxoaldehydes43 and reso-
lution of N-protected amino acid esters.44 Since the mechanism
of C. parapsilosis ATCC 7330 mediated deracemization involves
oxidation followed by reduction35 it was appropriate to develop
this biocatalyst as a good oxidizing agent for alcohols. Oxidative
kinetic resolution of secondary alcohols results in the formation
of a ketone along with an optically pure alcohol.30 Biocatalytic
oxidative kinetic resolution of allylic alcohols and 4-phenyl-
butan-2-ols is not widely reported in literature and this is the
aLaboratory of Bioorganic Chemistry, Department of Biotechnology, IIT Madras,
Chennai 600 036, India. E-mail: anjuc@iitm.ac.in; Fax: +91 44 2257 4102; Tel: +91
44 2257 4106
bFood and Process Engineering, School of Bioengineering, SRM University,
Kattankulathur 603203, India
cNational Center for Catalysis Research, Indian Institute of Technology Madras,
Chennai 600 036, India
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 2257–2262 | 2257

View Article Online
RSC Advances
Communication
In this study, the optimum temperature was found to be
20 ꢀC (conversion 41%) over a range of 15–40 ꢀC with 5 ꢀC
interval.
Studies on substrate structure
Under the standardised reaction conditions as mentioned
above, increase in the side chain length from ethyl to propyl
decreases the conversion to 9% and increases the reaction time
to 45 min in the case of (E)-1-phenylhex-1-en-3-ol 1b (Table 1).
Decrease of chain length from ethyl to methyl group 1c
(Scheme 1, Table 1) reduced the reaction time to 5 min from 25
min and increased the conversion to 49% to the corresponding
(E)-4-phenylbut-3-en-2-one 2c [yield 39%]. Similar observations
were reported for the oxidative kinetic resolution of short chain
alcohols.31
Scheme 1 Oxidative kinetic resolution of racemic allylic alcohols
1a–1g using whole cells of Candida parapsilosis ATCC 7330.
rst report on the enantioselective oxidation of allylic alcohols
and 4-phenylbutan-2-ols using whole cells of C. parapsilosis
ATCC 7330.
Results and discussion
Initial optimization studies [reaction time, substrate concen-
tration, co-solvent screening, pH and temperature] for the
oxidative kinetic resolution of secondary alcohols were carried
out with (E)-1-phenylpent-1-en-3-ol 1a as the model substrate
(Scheme 1) and the product, 2a was monitored by GC using a
DB-WAX column. Resolution of unreacted alcohols was carried
out by HPLC.
Effect of substitution on aromatic ring
Substitution of electron donating groups such as p-OCH3, p-CH3
on the aromatic ring showed increase in the conversion. For (E)-
4-(4-methoxyphenyl)but-3-en-2-ol 1d, conversion to the corre-
sponding (E)-4-(4-methoxyphenyl) but-3-en-2-one 2d was 55%
(yield 46%). (E)-4-p-Tolylbut-3-en-2-ol 1e showed similar
conversion (53%) to the corresponding (E)-4-p-tolylbut-3-en-2-
one 2e with a yield 42%. However, the electron withdrawing
group p-CN on (E)-4-(3-hydroxybut-1-enyl)benzonitrile 1f
Optimization studies
For the optimization of the reaction time, 14 h culture of C. decreases the conversion to 45% to the corresponding (E)-4-(3-
parapsilosis ATCC 7330 was used based on the earlier report.45 oxobut-1-enyl)benzonitrile 2f with a yield of 38%. In the case of
Reaction time for (E)-1-phenylpent-1-en-3-ol 1a was optimised p-Cl substitution 1g, 52% conversion to the corresponding p-Cl
over 15–40 min at constant substrate concentration (E)-4-phenylbut-3-en-2-one 2g (yield 42%) was seen.
(0.01 mM), at pH 7.0 and 25 ꢀC. The maximum conversion,
Here, it is noteworthy to mention that the same micro
37% was observed at 25 min. Using the above mentioned organism C. parapsilosis ATCC 7330 was reported earlier for
conditions, co-solvents DMSO (log P ¼ ꢁ1.35), 1, 4-dioxane deracemization of 1c to the optically pure (R) alcohol. The 44 h
(log P¼ ꢁ0.42), acetaldehyde (log P¼ ꢁ0.34), acetone (log culture takes a reaction time of 3 h25 (yield 75%, ee >99%) while
P¼ ꢁ0.042) and diisopropyl ether (log P¼ 1.4) were screened. the 14 h culture completes the reaction in 2 h47 yield 76%, ee
Among the solvents screened, acetone showed the maximum >99%). This reects the versatility of this Candida and the
conversion of 37%. Using acetone as co-solvent, further multitude of oxidoreductases which catalyse the biotransfor-
optimisation of pH and substrate concentration was carried mation of the same substrate under different reaction
out. It was observed that maximum conversion (39%) was conditions.
achieved at pH 6.5 and 0.02 mM substrate concentration. It is
Reaction time for the enantioselective oxidation of allylic
a well known fact that temperature of the reaction plays a alcohols (1c–1g) is only 5 min with an ee of up to >99%
vital role in biotransformation20 and needs to be optimised. compared to that of asymmetric aerobic oxidation of 1c to the
Table 1 Oxidative kinetic resolution of racemic allylic alcohols 1a–1g using whole cells of Candida parapsilosis ATCC 7330a
Substrate
Ketone (%)
2a–2g
Remaining alcohol
(%) 3a–3g
Yield
(%)
ee
(%)
Reaction
time (min)
Entry
R
R1
Yield (%)
Specic rotation (a)
1a
1b
1c
1d
1e
1f
H
H
H
CH2CH3
CH2CH2CH3
CH3
CH3
CH3
46
9
37
n.d.
39
46
42
38
42
54
91
51
45
48
55
48
50
n.d.
41
37
40
47
39
46
25
45
5
5
5
+1.50 (C 0.86, CHCl3)46
n.d.
n.d.
>99
>99
>99
>96
>99
49
55
53
45
52
+25.08 (C 0.66, CHCl3)25
+4.31 (C 0.73, CHCl3)25
+29.83 (C 0.33, CHCl3)25
+9.87 (C 1.33, CHCl3)b
+12.13 (C 1.16, CHCl3)25
p-OCH3
p-CH3
p-CN
p-Cl
CH3
CH3
5
5
1g
a
b
n.d.: not determined (As the conversion was very less in the case of 1g, yield and ee were not determined.). Absolute conguration was not
determined.
2258 | RSC Adv., 2014, 4, 2257–2262
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
case of 4-(4-chlorophenyl) butan-2-ol 4e increases the conver-
sion 55% to the corresponding 4-(4-chlorophenyl) butan-2-one
5e and a yield of 46% in 7 h. To the best of our knowledge so far
no reports are available for both, chemical as well bio catalytic
oxidative kinetic resolution for 4c, 4d and 4e. This is the rst
report (Table 2, Scheme 2).
Scheme 2 Oxidative kinetic resolution of racemic 4-phenylbutan-2-
ols 4a–4e using whole cells of Candida parapsilosis ATCC 7330.
Experimental
corresponding optically pure (R) alcohol which was reported
using optically active (nitroso) (salen) ruthenium(II) chloride, in
air with a uorescent lamp in 17 h to give an ee >97%.48 The
oxidative kinetic resolution of 1c to the optically pure (R) alcohol
[ee 90% and yield 41%] was reported using iron (salan) complex
in 36 h at 50 ꢀC.49 To the best of our knowledge oxidative kinetic
resolution of (E)-4-(3-hydroxybut-1-enyl) benzonitrile 1f
(Scheme 1, Table 1) is reported here for the rst time and it is
biocatalyst mediated.
All substituted benzaldehydes, Pd/C were bought from Spec-
trochem and acetone from Merck. Substituted (E)-4-phenyl
but-3-en-2-ols (1a–1e),52,53 (E)-1-phenylpent-1-en-3-ol 1f, (E)-1-
phenylhex-1-en-3-ol 1g54 and substituted 4-phenylbutan 2-ols
(4a–4e)55 were synthesized using literature reported methods.
Conversion of (E)-4-phenylbut-3-en-2-ols, 4-phenylbutan-2-ol,
1-phenylpent-1-en-3-ol
and
1-phenylhex-1-en-3-ol
were
checked by GC using DB-WAX column (30 m ꢂ 0.25 mm ꢂ
0.50 mm). GC conditions are as follows: injector temperature:
240 ꢀC, oven temperature: 250 ꢀC, split: 1 : 10, carrier gas:
Oxidative kinetic resolution of substituted 4-phenylbutan-2-ols
helium, ow: 3 mL minꢁ1. GC program: 90 C hold for 1 min,
ꢀ
4-Phenylbutan-2-ol 4a (Scheme 2, Table 2),
a saturated
at the rate 3 ꢀC minꢁ1 to 200 ꢀC, hold for 15 min. The
conversion of substituted allylic alcohols and substituted 4-
phenylbutan-2-ols was determined by Jasco PU-1580 HPLC
equipped with PDA detector, using reverse phase C18
column, acetonitrile : water (60 : 40) mixture as mobile phase
with 0.5 mL minꢁ1 ow rate. Enantiomeric excess was
determined by HPLC using Daicel chiralcel OD-H, OJ-H and
OB-H columns and Chiralpak AD-H (Daicel) column. Hex-
ane : isopropanol mixture was used as mobile phase. Mobile
phase ratio and ow rate varied for different substituted
alcohols. Infrared spectra were recorded on a JASCO FT/IR-
4200 instrument. Mass spectra were recorded on a Micro Q-
Tof mass spectrometer using the ESI technique. Optical
rotations were recorded on Rudolph, Autopol IV digital
secondary alcohol when subjected to the biotransformation
took longer (reaction time 4 h) unlike allylic alcohols, possibly
due to the absence of double bonds which are known to
facilitate hydride abstraction in the case of allylic alcohols.50
Conversion of 4-phenylbutan-2-ol 4a to the corresponding 4-
phenylbutan-2-one 5a was 50% and the yield was 41% which is
better than that reported earlier i.e. the resolution of 4-phe-
nylbutan-2-ol using Yarrowia lipolytica 8661 [yield 22% ee
95%], Rhodotorula mucilaginosa 4056 [yield 41% and ee 89%]
and Candida parapsilosis 16632 [yield 32% and ee 85%] in
24–72 h.51
Effect of substitution on aromatic ring
1
polarimeter. H and 13C NMR spectra were recorded in CDCl3
Electron donating groups such as p-OCH3, p-CH3 on the
aromatic ring of 4-phenylbutan-2-ol 4a showed signicant
increase in the reaction time for the oxidative kinetic resolution.
Substitution of p-OCH3 in the case of 4-(4-methoxyphenyl)
butan-2-ol 4b increases the reaction time to 11 h with conver-
sion of 50% (yield 42%) to the corresponding 4-(4-methoxy-
on Bruker AVANCE III 500 MHz spectrometer operating at
500 and 125 MHz.
Maintenance and cultivation of C. parapsilosis ATCC 7330
phenyl)butan-2-one 5b. In the case of 4-p-tolylbutan-2-ol 4c the C. parapsilosis ATCC 7330 was purchased from American Type
reaction time was 9 h with conversion of 52% to the corre- Culture Collection, Manassas, VA 20108, USA and maintained at
ꢀ
sponding 4-p-tolylbutan-2-one 5c and a yield of 43%.
4 C in yeast malt agar medium (Himedia product). All ingre-
The electron withdrawing group, p-CN in 4d decreases the dients used for media preparation were purchased locally.
C. parapsilosis ATCC 7330 was grown and harvested as
conversion to 43% to the corresponding 4-(3-oxobutyl) benzo-
nitrile 5d and the yield is 37% in 7 h. Substitution of p-Cl in the reported earlier45 and used for biotransformation.
Table 2 Oxidative kinetic resolution of racemic 4-phenylbutan-2-ols 4a–4e using whole cells of Candida parapsilosis ATCC 7330
Ketonea
(%) 5a–5e
Yield
(%)
Remaining alcohol
(%) 6a–6e
S. no.
Substrate
Yield (%)
ee (%)
Reaction time (h)
Specic rotation (a)
4a
4b
4c
4d
4e
H
50
50
52
43
55
41
42
43
37
46
50
50
48
57
45
42
42
41
52
37
>99
>99
>99
86
4
11
9
7
7
ꢁ15.00 (C 0.6, CHCl3)56
ꢁ31.53 (C 0.33, CHCl3)57
ꢁ22.10 (C 0.27, CHCl3)b
ꢁ21.56 (C 0.73, CHCl3)b
ꢁ32.50 (C 0.4, CHCl3)b
p-OCH3
p-CH3
p-CN
p-Cl
>99
Conversion was checked by HPLC on C-18 column. b Absolute conguration was not determined (specic rotation is not reported).
a
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 2257–2262 | 2259

View Article Online
RSC Advances
Communication
4-(4-Methoxyphenyl) butan-2-ol (6b): OD-H column [hexanes/
2-propanol ¼ 98 : 02, 1.0 mL minꢁ1; retention times 21.49 min
(R-major), 25.29 min (S-minor)].
4-p-Tolylbutan-2-ol (6c): AD-H column [hexanes/2-propanol ¼
98 : 02, 1.0 mL minꢁ1; retention times 12.15 min (S-minor),
13.44 min (R-major)].
General procedures for biocatalytic enantioselective oxidation
Wet cells (6.5 g) of C. parapsilosis ATCC 7330 were suspended in
32.5 mL of phosphate buffer (pH 6.5, 10 mM). (E)-4-phenyl but-
3-en-2-ol 1a (0.1 mM) dissolved in 1 mL acetone was added to
the cell suspension, incubated at 20 ꢀC, 150 rpm for 5 min. The
products 2a and 3a were extracted with ethyl acetate 3 ꢂ 10 mL,
dried over anhydrous sodium sulphate and concentrated using
rotary evaporator. Conversion was checked using GC on DB Wax
column (Table 1). Isolated yield for the products was deter-
mined aer column chromatography using hexane : ethyl
acetate (98 : 02) as eluent.
The same procedure was used for the other alcohols 1b–1g
(Table 1, Scheme 1) and 4a–4e (Scheme 2, Table 2) with subse-
quent change in the reaction time for the oxidative kinetic
resolution using C. parapsilosis ATCC 7330. The reactions were
repeated in triplicate for consistent results and control experi-
ments were done in parallel without the whole cells and also
using dead cells under identical conditions. The absolute
congurations for all the optically pure alcohols were assigned
to be (R).
4-(3-Hydroxybutyl)benzonitrile (6d): 1H NMR (CDCl3, 500
MHz) d ppm: 1.23–1.24 (d, 3H), 1.52 (s, 1H), 1.73–1.78 (m, 2H),
2.70–2.76 (m, 1H), 2.80–2.86 (m, 1H), 3.78–3.84 (m, 1H), 7.29–
7.31 (m, 2H) 7.55–7.57 (m, 2H); 13C NMR (CDCl3, 125 MHz) d
ppm:23.79, 32.26, 40.16, 67.14, 109.69, 119.08, 129.24, 132.22,
147.95; HRMS [EI] calculated for C11H14NO: (M + H)+
¼
176.1075 found (M + H)+ ¼ 176.1067. IR: 3410, 2966, 2228, 1607,
1185, 1131, 827, 737, 485, 467 cmꢁ1. Resolution: AD-H column
[hexanes/2-propanol ¼ 95 : 05, 1.0 mL minꢁ1; retention times
18.96 min (S-minor), 20.15 min (R-major)].
4-(4-Chlorophenyl) butan-2-ol (6e): OB-H column [hexanes/2-
propanol ¼ 98 : 02, 1.0 mL minꢁ1; retention times 10.83 min
(S-minor), 12.85 min (R-major)].
Conclusion
Spectral data of products
C. parapsilosis ATCC 7330 is reported rst time for the enan-
Spectral data for the compounds 2a,58 2c,58 2d,58 2e,58 2f,59 2g,58 tioselective oxidation of secondary alcohols. Substituted (E)-4-
3a,60 3c,56 3d,56 3e,25 3g,25 5a,61 5b,62 5c,61 5d,63 5e,64 6a,65 6b,66 6c67 phenylbut-3-en-2-ones (conversion 9–55%, yield 37–46%),
and 6e68 were consistent with the earlier report. For all substituted 4-phenyl 2-butanones (conversion 43–55%, yield
compounds resolution was done by HPLC. Details are given 37–46%) are reported via enantioselective oxidation using the
below.
whole cells of C. parapsilosis ATCC 7330 under optimised
(E)-1-Phenylpent-1-en-3-ol (3a): OD-H column [hexanes/2- reaction conditions (20 ꢀC and pH 6.5). The corresponding
propanol ¼ 95 : 05, 1.0 mL minꢁ1; retention times 11.03 min (R- unreacted alcohols (R) (E)-4-phenylbut-3-en-2-ols (yield 37–50%,
major), 18.25 min (S-minor)].
ee 96–>99%), substituted (R)-4-phenylbutan-2-ols (yield 37–
(E)-4-Phenylbut-3-en-2-ol (3c): OD-H column [hexanes/2- 52%, ee 86–>99%) are thus formed in optically pure form.
propanol ¼ 95 : 05, 1.0 mL minꢁ1; retention times 12.68 min (R-
(E)-4-(3-Hydroxybut-1-enyl) benzonitrile 1f, 4-p-tolylbutan-2-
ol 4c, 4-(3-hydroxybutyl)benzonitrile 4d, 4-(4-chlorophenyl)
major), 20.12 min (S-minor)].
(E)-4-(4-Methoxyphenyl) but-3-en-2-ol (3d): OJ-H column butan-2-ol 4e alcohols are reported here for the rst time. In the
[hexanes/2-propanol ¼ 90 : 10, 1.0 mL minꢁ1; retention times case of aryl allylic alcohols, substitution on the aromatic ring
16.97 min (S-minor), 20.28 min (R-major)].
did not show much effect on oxidation. 4-phenylbutan-2-ols
(E)-4-p-Tolylbut-3-en-2-ol (3e): OJ-H column [hexanes/2-prop- unlike allylic alcohols showed increase in the reaction time
anol ¼ 95 : 05, 1.0 mL minꢁ1; retention times 13.20 min from 4 to 11 h depending upon the substituent. Electron
(S-minor), 15.65 min (R-major)].
donating groups p-OMe and p-Me took longer reaction times (11
(E)-4-(3-Hydroxybut-1-enyl)benzonitrile (3f): 1H NMR (CDCl3, h, 9 h respectively) compared to that taken by electron with-
500 MHz) d ppm: 1.35–1.36 (d, 3H, J ¼ 6.0), 2.34 (s, 1H), 4.47– drawing groups p-CN, p-Cl (7 h).
4.52 (m, 1H), 6.35–6.39 (dd, 1H, J ¼ 16, J ¼ 6 Hz), 6.55–6.58 (dd,
1H, J ¼ 16, J¼ 1 Hz), 7.40–7.42 (m, 2H), 7.53–7.55 (m, 2H). 13C
Acknowledgements
NMR (CDCl3, 125 MHz) d ppm: 23.35, 68.27, 110.58, 118.95,
126.91, 127.32, 132.39, 137.69, 141.46; HRMS [EI] calculated for T. Sivakumari thanks Council of Scientic and Industrial
C
11H12NO: (M + H)+ ¼ 174.0919 found (M + H)+ ¼ 174.0926. IR: research (CSIR, India) for fellowship. We thank the Sophisti-
3423, 2972, 2359, 2227, 1649, 1605, 1506, 1410, 1142, 1059, 971, cated Analytical Instrumentation Facility (SAIF), IIT Madras,
814, 552, 444 cmꢁ1. Resolution: OJ-H column [hexanes/2-prop- Department of Chemistry, IIT Madras for the NMR and Mass
anol ¼ 90 : 10, 1.0 mL minꢁ1; retention times 15.09 min analysis and the Department of Biotechnology, New Delhi,
(S-minor), 17.40 min (R-major)].
India. R. Preetha thanks Department of Science and Technology
(E)-4-(4-Chlorophenyl) but-3-en-2-ol (3g): OB-H column (DST, India) for WOS-A fellowship.
[hexanes/2-propanol ¼ 95 : 05, 1.0 mL minꢁ1; retention times
8.64 min (S-minor), 10.45 min (R-major)].
Notes and references
4-Phenyl butan 2-ol (6a): OD-H column [hexanes/2-propanol ¼
95 : 05, 1.0 mL minꢁ1; retention times 8.93 min (R-major), 12.83
min (S-minor)].
1 S. Marcaccini, A. G. Neo and C. F. Marcos, J. Org. Chem.,
2009, 74, 6888–6890.
2260 | RSC Adv., 2014, 4, 2257–2262
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
2 M. Z. Zhao, J. Li, Z. G. Song, R. Desmond, D. M. Tschaen, 28 L. H. Andrade, R. S. Utsunomiya, A. T. Omori, A. L. M. Porto
E. J. J. Grabowski and P. J. Reider, Tetrahedron Lett., 1998,
39, 5323–5326.
3 S. R. Reddy, S. Stella and A. Chadha, Synth. Commun., 2012,
42, 3493–3503.
and J. V. Comasseto, J. Mol. Catal. B: Enzym., 2006, 38, 84–90.
29 K. Edegger, W. Stampfer, B. Seisser, K. Faber, S. F. Mayer,
R. Oehrlein, A. Hafner and W. Kroutil, Eur. J. Org. Chem.,
2006, 1904–1909.
´
¨
4 G. Csjernyik, A. H. Ell, L. Fadini, B. Pugin and J.-E. Backvall, 30 G. Fantin, M. Fogagnolo, A. Medici, P. Pedrini and
J. Org. Chem., 2002, 67, 1657–1662. S. Fontana, Tetrahedron: Asymmetry, 2000, 11, 2367–2373.
5 S. V. O'Neil, C. A. Quickley and B. B. Snider, J. Org. Chem., 31 W. Stampfer, B. Kosjek, K. Faber and W. Kroutil,
1997, 62, 1970–1975. Tetrahedron: Asymmetry, 2003, 14, 275–280.
6 C. Garcia-Burgos, J. D. Carballeira and J. V. Sinisterra, J. Mol. 32 H. I. Perez, H. Luna, N. Manjarrez and A. Solıs, Tetrahedron:
´
´
Catal. B: Enzym., 2006, 41, 16–20.
Asymmetry, 2001, 12, 1709–1712.
7 X. Jia, Y. Xu and Z. Li, ACS Catal., 2011, 1, 591–596.
33 F. EscalettesandN. J. Turner, ChemBioChem, 2008, 9, 857–860.
8 M. Nagaki, H. Imaruoka, J. Kawakami, K. Saga, H. Kitahara, 34 K. Edegger, H. Mang, K. Faber, J. Gross and W. Kroutil,
H. Sagami, R. Oba, N. Ohya and T. Koyama, J. Mol. Catal. B:
Enzym., 2007, 47, 33–36.
9 R. Villa, A. Romano, R. Gandol, J. V. S. Gago and
F. Molinari, Tetrahedron Lett., 2002, 43, 6059–6061.
10 E. Baciocchi, O. Lanzalunga and L. Manduchi, Chem.
Commun., 1999, 1715–1716.
11 L. F. Blackwell and M. J. Hardman, Eur. J. Biochem., 1975, 55,
611–615.
12 M. Fabbrini, C. Galli and P. Gentili, J. Mol. Catal. B: Enzym.,
2002, 16, 231–240.
J. Mol. Catal. A: Chem., 2006, 251, 66–70.
35 B. Baskar, N. G. Pandian, K. Priya and A. Chadha,
Tetrahedron, 2005, 61, 12296–12306.
36 A. Chadha and B. Baskar, Tetrahedron: Asymmetry, 2002, 13,
1461–1464.
37 S. K. Padhi, N. G. Pandian and A. Chadha, J. Mol. Catal. B:
Enzym., 2004, 29, 25–29.
38 T. Saravanan and A. Chadha, Tetrahedron: Asymmetry, 2010,
21, 2973–2980.
39 B. Baskar, N. G. Pandian, K. Priya and A. Chadha,
Tetrahedron: Asymmetry, 2004, 15, 3961–3966.
40 T. Kaliaperumal, S. N. Gummadi and A. Chadha,
Tetrahedron: Asymmetry, 2011, 22, 1548–1552.
41 T. Vaijayanthi and A. Chadha, Tetrahedron: Asymmetry, 2008,
19, 93–96.
13 V. Hollrigl, F. Hollmann, A. C. Kleeb, K. Buehler and
A. Schmid, Appl. Microbiol. Biotechnol., 2008, 81, 263–273.
14 E. Kiljunen and L. T. Kanerva, J. Mol. Catal. B: Enzym., 2000,
9, 163–172.
15 I. Lavandera, A. Kern, V. Resch, B. Ferreira-Silva, A. Glieder,
W. M. F. Fabian, S. de Wildeman and W. Kroutil, Org. Lett., 42 S. Stella and A. Chadha, Catal. Today, 2012, 198, 345–352.
2008, 10, 2155–2158.
16 E. W. van Hellemond, L. Vermote, W. Koolen, T. Sonke,
43 P. Mahajabeen and A. Chadha, Tetrahedron: Asymmetry,
2011, 22, 2156–2160.
E. Zandvoort, D. Heuts, D. B. Janssen and M. W. Fraaije, 44 S. Stella and A. Chadha, Tetrahedron: Asymmetry, 2010, 21,
Adv. Synth. Catal., 2009, 351, 1523–1530. 457–460.
17 K. Kawakami and S. Y. Furukawa, Appl. Biochem. Biotechnol., 45 T. Kaliaperumal, S. Kumar, S. N. Gummadi and A. Chadha,
1997, 67, 23–31. J. Ind. Microbiol. Biotechnol., 2010, 37, 159–165.
18 T. Orbegozo, J. G. de Vries and W. Kroutil, Eur. J. Org. Chem., 46 P. Peach, D. J. Cross, J. A. Kenny, I. Mann, I. Houson,
2010, 3445–3448.
L. Campbell, T. Walsgrove and M. Wills, Tetrahedron, 2006,
62, 1864–1876.
47 T. Saravanan, R. Selvakumar, M. Doble and A. Chadha,
Tetrahedron: Asymmetry, 2012, 23, 1360–1368.
48 K. Masutani, T. Uchida, R. Irie and T. Katsuki, Tetrahedron
Lett., 2000, 41, 5119–5123.
19 H. I. Perez, N. Manjarrez, A. Solis, H. Luna, M. A. Ramirez
and J. Cassani, Afr. J. Biotechnol., 2009, 8, 2279–2282.
20 W. Kroutil, H. Mang, K. Edegger and K. Faber, Curr. Opin.
Chem. Biol., 2004, 8, 120–126.
21 K. Edegger, H. Mang, K. Faber, J. Gross and W. Kroutil,
J. Mol. Catal. A: Chem., 2006, 251, 66–70.
49 T. Kunisu, T. Oguma and T. Katsuki, J. Am. Chem. Soc., 2011,
133, 12937–12939.
22 T. Orbegozo, I. Lavandera, W. M. F. Fabian, B. Mautner,
J. G. de Vries and W. Kroutil, Tetrahedron, 2009, 65, 6805– 50 D. Liaigre, T. Breton and E. M. Beigsir, Electrochem.
6809. Commun., 2005, 7, 312–316.
23 H. Wu, C. Tian, X. Song, C. Liu, D. Yang and Z. Jiang, Green 51 M. J. Homann, R. B. Vail, E. Previte, M. Tamarez, B. Morgan,
Chem., 2013, 15, 1773–1789. D. R. Dodds and A. Zaks, Tetrahedron, 2004, 60, 789–797.
24 A. Dhariwal, V. Mavrov and I. Schroeder, J. Mol. Catal. B: 52 S. W. Chaikin and W. G. Brown, J. Am. Chem. Soc., 1949, 71,
Enzym., 2006, 42, 64–69. 122–125.
25 D. Titu and A. Chadha, Tetrahedron: Asymmetry, 2008, 19, 53 K. Zumbansen, A. Dohring and B. List, Adv. Synth. Catal.,
1698–1701. 2010, 352, 1135–1138.
26 H. Groger, W. Hummel, C. Rollmann, F. Chamouleau, 54 L. Williams, Z. Zhang, S. Feng, P. J. Carroll and M. M. Joullie,
¨
´
¨
H. Husken, H. Werner, C. Wunderlich, K. Abokitse,
Tetrahedron, 1996, 52, 11673–11694.
55 G. S. Vanier, Synlett, 2007, 131–135.
K. Drauz and S. Buchholz, Tetrahedron, 2004, 60, 633–640.
27 B. Kosjek, W. Stampfer, R. v. Deursen, K. Faber and 56 P. He, X. Liu, H. Zheng, W. Li, L. Lin and X. Feng, Org. Lett.,
W. Kroutil, Tetrahedron, 2003, 59, 9517–9521.
2012, 14, 5134–5137.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 2257–2262 | 2261

View Article Online
RSC Advances
Communication
57 A. Boffi, S. Cacchi, P. Ceci, R. Cirilli, G. Fabrizi, A. Prastaro, 63 S. Condon, D. Dupre, G. Falgayrac and J. Y. Nedelec, Eur. J.
S. Niembro, A. Shar and A. Vallribera, ChemCatChem,
2011, 3, 347–353.
58 M. McConville, O. Saidi, J. Blacker and J. Xiao, J. Org. Chem.,
2009, 74, 2692–2698.
59 P. S.-W. Leung, Y. Teng and P. H. Toy, Org. Lett., 2010, 12,
4996–4999.
60 X.-F. Yang, T. Hirose and G.-Y. Zhang, Tetrahedron:
Asymmetry, 2008, 19, 1670–1675.
Org. Chem., 2002, 105–111.
64 A. Mori, Y. Miyakawa, E. Ohashi, T. Haga, T. Maegawa and
H. Sajiki, Org. Lett., 2006, 8, 3279–3281.
65 S. S. Murphree, J. D. Mason, T. G. Bean and M. C. Perry,
Synth. Commun., 2011, 42, 1979–1986.
66 R. Larouche-Gauthier, T. G. Elford and V. K. Aggarwal, J. Am.
Chem. Soc., 2011, 133, 16794–16797.
67 L. Shi, Y.-Q. Tu, M. Wang, F.-M. Zhang, C.-A. Fan, Y.-M. Zhao
and W.-J. Xia, J. Am. Chem. Soc., 2005, 127, 10836–10837.
68 Q. Zhao, D. P. Curran, M. Malacria, L. Fensterbank,
61 Y. Onishi, Y. Nishimoto, M. Yasuda and A. Baba, Org. Lett.,
2011, 13, 2762–2765.
ˆ
62 F. Berthiol, H. Doucet and M. Santelli, Tetrahedron, 2006, 62,
4372–4383.
J.-P. Goddard and E. Lacote, Chem.–Eur. J., 2011, 17, 9911–
9914.
2262 | RSC Adv., 2014, 4, 2257–2262
This journal is © The Royal Society of Chemistry 2014