Daucus carota and baker's yeast mediated bio-reduction of prochiral ketones

Article abstract of DOI:10.1016/j.tetasy.2007.03.009

Stereoselective reduction of prochiral ketones to the corresponding alcohols using biocatalysts has attracted much attention, from the viewpoint of green chemistry. Asymmetric reduction of indanone, tetralone and hydroxyl trimonoterpene ketones to the corresponding enantiomerically pure (S)-alcohols, using Daucus carota plant homogenate and fermented baker's yeast cells, is described. The present study illustrates the broad substrate selectivity of the dehydrogenase enzymes present in the D. carota in the synthesis of a wide range of chiral secondary alcohols of biological importance.

Full text of DOI:10.1016/j.tetasy.2007.03.009

Tetrahedron: Asymmetry 18 (2007) 717–723
Daucus carota and baker’s yeast mediated bio-reduction
of prochiral ketonesI
Jhillu S. Yadav, Garudammagari S. K. K. Reddy, Gowravaram Sabitha, Avvaru D. Krishna,
Attaluri R. Prasad, Hafeez-U-R-Rahaman, Katta Vishwaswar Rao and Adari Bhaskar Rao*
Organic Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 15 December 2006; accepted 7 March 2007
Abstract—Stereoselective reduction of prochiral ketones to the corresponding alcohols using biocatalysts has attracted much attention,
from the viewpoint of green chemistry. Asymmetric reduction of indanone, tetralone and hydroxyl trimonoterpene ketones to the cor-
responding enantiomerically pure (S)-alcohols, using Daucus carota plant homogenate and fermented baker’s yeast cells, is described.
The present study illustrates the broad substrate selectivity of the dehydrogenase enzymes present in the D. carota in the synthesis of
a wide range of chiral secondary alcohols of biological importance.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
for the organic chemists in addition to baker’s yeast cells in
the synthesis of homochiral secondary alcohols.6 Herein we
report a non-conventional simple asymmetric bio-reduc-
tion of prochiral ketones to corresponding alcohols of bio-
logical importance.
Asymmetric reduction of prochiral ketones into chiral non-
racemic secondary alcohols is a fundamental process in the
synthesis of organic molecules of biological interest.1 Chi-
ral alcohols are versatile building blocks for a number of
natural and unnatural compounds used in the synthesis
of pharmaceuticals, agrochemicals, pheromones, flavors,
fragrances and can also act as chiral auxiliaries in asym-
metric synthesis of chiral molecules.2 Though numerous
chemical and biological methodologies are known in the
synthesis of these secondary chiral alcohols, difficulties still
remain in attaining high yields and enantiomeric excess due
to the use of expensive chiral reagents (chemical /metal cat-
alysts) and in isolation of pure product from reaction/fer-
mentation medium.3 Biocatalysts catalyze the reactions,
in aqueous medium under mild and economically viable
conditions, in a eco-friendly environment when compared
to chemical (homogeneous and heterogeneous) or organo
metallic catalysts used in chemical reactions.4 Recently,
plant cell cultures/cut carrot root homogenates have been
used in transformation of the exogenous substrates.5 In
our earlier articles, we reported the reduction of prochiral
ketones using Daucus carota homogenate as a further tool
2. Results and discussion
D. carota and baker’s yeast cells show promising redox po-
tential in catalyzing prochiral ketones, indanones, tetralone
and terpenoids. Herein we explore the potential usefulness
of the enzymes dehydrogenases in the reduction of
carbonyl groups with broad substrate specificity and
high yields to corresponding alcohols of biological
significance.
2.1. Reduction of substituted 1-oximino indanones to
substituted 1-amino-2-indanol
The asymmetric reductions of the substituted 1-oximino
indanones 4a–d and 10a–b were carried out using D. carota
or baker’s yeast cells (Schemes 1 and 2) to obtain pure
substituted cis-2-hydroxy-1-indanone-oximes 5a–d and
11a–b, with high stereoselectivities and yields. Thus the ob-
tained oximes are subjected to hydrogenation to give the
corresponding target molecule of substituted cis-(1R,2S)-
1-amino-2-indanols 6a–d and 12a–b with excellent isolated
yield, diastereoselectivity and enantiomeric excess (Table
q Part of the work granted US Patent.6c
Corresponding author. Tel.: +91 040 27193374; fax: +91 040
*
27160512; e-mail: adarirao2002@Yahoo.co.in
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.03.009

718
J. S. Yadav et al. / Tetrahedron: Asymmetry 18 (2007) 717–723
R2
R2
R2
O
c
a
b
O
3
1
2
R1
R2
R1
R1
HO
HO
R2
N
R2
N
NH2
d
e
O
OH
OH
R1
R1
R1
4
5
6
Scheme 1. Synthesis of substituted cis-1-amino-2-indanols: Reagents and conditions: (a) MCPBA, DCM, rt; (b) HNO3, IBX; (c) isoamyl nitrite, TMSCl,
ꢀ20 ꢁC; (d) biocatalyst (D carota or Baker’s yeast), 0.1 mM phosphate buffer, pH 6.5; (e) 10% Pd/C, H2/MeOH. Compounds (6a) R1 = R2 = H; (6b)
R2 = Me; (6c) R1 = Me; (6d), R2 = (CH3)2CH.
R4
b
a
R4
R3
c
OAc
OAc
O
R3
8
7
9
HO
HO
NH2
N
N
R4
R3
d
e
R4
R3
R4
R3
O
OH
OH
11
12
10
Scheme 2. Synthesis of substituted cis-1-amino-2-indanols: Reagents and conditions: (a) NBS, (1 equiv) CH3CN, 25 ꢁC for mono bromo and NBS
(2 equiv), Br2 (1.1 equiv), CH3CN 0–25 ꢁC; (b) 10% aq NaOH, MeOH, 0–25ꢁC; (2) IBX, CH3CN, rt; (c) isoamyl nitrite, TMSCl, ꢀ20 ꢁC; (d) biocatalyst
(D. carota or Baker’s yeast), 0.1 mM phosphate buffer, pH 6.5; (e) 10% Pd/C, H2/MeOH. Compounds (12a) R3 = Br; (12b) R3, R4 = Br.
Table 1. Reduction of substituted 2-indanones
Entry
Product
Daucus carota
Baker’s yeast
Time (h)
Conversion (%)
ee%
Configuration
Time (h)
Conversion (%)
ee%
Configuration
1
2
3
4
5
6
6a
6b
6
18
20
28
24
24
95
75
70
45
80
75
99
98
95
90
95
96
S
S
S
S
S
S
8
20
24
72
48
48
85
72
75
60
65
65
88
90
92
77
89
91
S
S
S
S
S
S
6c
6d
12a
12b
(a) Absolute configuration was determined by optical rotation or by 1H NMR by preparing Mosher esters of the products.
(b) The specific activity of the enzyme carbonyl reductase present in (i) D. carota 245 mmol minꢀ1, mgꢀ1 protein (protein 15 lg/ml); (ii) yeast
465 mmol minꢀ1, mgꢀ1 protein (protein 25 lg/ml).
1). The stereochemistry of cis-(S)-2-hydroxy-1-indanone-
oxime 5a is confirmed by derivatising the compound to ace-
tate to give (E)-(S)-2-acetoxy-1-acetoxyiminoindanol and
the spectrum was compared with reported values,7b thus
the obtained (E)-(S)-2-acetoxy-1-acetoxyiminoindanol re-
crystallized from ethyl acetate/hexane (5:95) gave white
crystals. Mp 117–119 ꢁC IR (neat): m 1778, 1765, 1633,
1603 1461, 1338, 1365, 1254, 1233, 1032, 924, 829. 1H
NMR (CDCl3, 200 MHz): d 2.10 (s, 3H), 2.35 (s, 3H),
3.0 (d, 1H, J = 17.5 Hz), 3.60 (dd, 1H, J = 7.5, 17.5 Hz),
5.90 (m, 1H) multiplet for EH proton, 7.35 (t, 2H,
J = 7.8 Hz), 7.48 (t, 1H, J = 7.8 Hz), 8.21 (d, 1H,

J. S. Yadav et al. / Tetrahedron: Asymmetry 18 (2007) 717–723
719
J = 8.0 Hz) EIMS: m/z: 206 M+. Anal. Calcd for
ogy developed is simple and easy in the synthesis of
important chiral tetralols and is of great significance since
some of these are key intermediates in the synthesis of bio-
logically active molecules.12
C11H11NO3: C, 64.38; H, 5.40; N, 6.83. Found: C, 63.04;
25
H 5.32; N, 6.80. Specific rotation ½aꢁD ¼ þ65:5 (c 0.8,
MeOH), optical purity 96% ee.
From the results obtained (Table 1), it was observed that
the D. carota plant homogenate shows good enantioselec-
tivity in the chiral reduction of the indanones in compari-
son with yeast cells. This method provides an efficient
route in the synthesis of enantiomerically pure 1-amino-2-
indanol, which is somewhat difficult to obtain by chemical
methods.8 From the optical studies, it was concluded that
the bio-reduction of cis-(S)-2-hydroxy-1-indanone-oxime
to the corresponding secondary amino alcohols exclusively
gave an (S)-configuration with yields ranging from 80% to
90%, diastereomeric purity of >95–98%. In comparison
with the chemical synthesis of enantiomerically pure cis-
1-amino-2-indanol, the use of D. carota root homogenate
as a source of the biocatalyst for the bio-reduction pro-
cesses is simple and economical, and showed high enanti-
oselectivity.9 The present methodology describes the
synthesis/design of a number of natural/synthetic conven-
tional chiral indole libraries and chiral ligands for
advanced asymmetric reactions.10
2.3. Reduction of monoterpene ketones
The monoterpenes of the p-menthane family are widely
spread in Nature and exhibit significant biological activities
such as perfumery, flavor and herbicide and in the pharma-
ceutical industry.13 Biotransformation of monoterpene
ketones 15, 17 and 20 to the corresponding alcohols is stud-
ied (Scheme 4). It was observed from the results in Table 3
that the D. carota plant enzymes and yeast cells reduced
both C–C double bonds and the carbonyl group present
in the terpenoids pharmacophores 17 and 20. Thus the
enzyme present in D. carota and yeast cells showed broad
substrate specificity, good yields (80–90%) and enantio-
selectivities (88–99%).
The bio reduction of the carbonyl groups studied by the
carrot and baker’s yeast cell systems proceeded stereoselec-
tively, following Prelog’s rule, which resulted in the pre-
dominant formation of (S)-alcohols.14 The repetitive use
of the carrot root homogenate was attempted on the bio-
transformation of the prochiral ketones, where it was ob-
served that the bio-catalytic activity of the carrot root
homogenate maintained after 3–4 consecutive reuses high
chemical yields and enantiomeric excesses.15 The use of
D. carota in asymmetric bio-reduction was accompanied
by several limitations such as the large biocatalyst to
substrate (B/S) ratios, thus effecting conversion and com-
mercial application. Work is currently in progress to over-
come these difficulties by natural genetic transformation.16
2.2. Reduction of cyclic ketones (tetralones)
The enantioselective reductions of substituted 2-tetralone
were studied using D. carota and yeast cells (Scheme 3).
From the results obtained (Table 2), it was observed that
the D. carota homogenate reduced compounds 13a–c in
modest yields (50–60%) and enantioselectivity (70–80%)
with long incubation periods. In comparison with earlier
studies on the bio-reduction of tetralones, the present study
using D. carota homogenate and fermented yeast cells pro-
duced good yields and enantioselectivity.11 The methodol-
3. Conclusions
R3
R3
Bio-reduction catalyzed by dehydrogenases enzymes
present in D. carota and yeast cells provides an attractive
approach in selectively reducing a broad range of ketone
substrates with excellent yields and selectivity. Intact cells
from cut portion plants can mediate useful asymmetric
transformations, thus offering new possibilities to synthetic
chemists in terms of simplicity, efficiency and cost (in the
absence of an external addition of coenzyme NAD (P) H
to the medium). This methodology could also provide as
a new tool for bio-reduction and exploitation of the bio-
mass mainly towards production of functional molecules
of biological importance.
H
O
R2
R2
OH
a
R1
R1
13
14
Scheme 3. Synthesis of substituted tetralols. Reagents and conditions: (a)
biocatalyst (D. carota or Baker’s yeast), 0.1 mM phosphate buffer pH 6.5.
Compounds (14a) R1, R2, R3 = H; (14b) R2 = OCH3; (14c) R2 =
R3 = OCH3.
Table 2. Reduction of cyclic ketones
Entry
Product
Daucus carota
Baker’s yeast
Time (h)
Conversion (%)
ee%
Configuration
Time (h)
Conversion (%)
ee%
Configuration
1
2
3
14a
14b
14c
36
40
62
45
40
40
85
70
80
S
S
S
96
72
72
35
30
40
70
70
75
S
S
S
(a) Absolute configuration was determined by specific rotation or by 1H NMR by preparing Mosher Esters of the products.
(b) The specific activity of the enzyme carbonyl reductase present in (i) D. carota 245 mmol minꢀ1, mgꢀ1 protein (protein 15 lg/ml); (ii) yeast
465 mmol minꢀ1, mgꢀ1 protein (protein 25 lg/ml).

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J. S. Yadav et al. / Tetrahedron: Asymmetry 18 (2007) 717–723
a
O
OH
15
16
O
O
OH
a
a
18
19
17
a
a
O
OH
OH
Scheme 4. Synthesis of mono terpenols. Reagents and conditions: (a) biocatalyst (D. carota or Baker’s yeast), 0.1 mM phosphate buffer pH 6.5.
Table 3. Reduction of terpenoid ketones
Entry
Product
Daucus carota
Baker’s yeast
Time (h)
Conversion (%)
ee%
Configuration
Time (h)
Conversion (%)
ee%
Configuration
1
2
3
16
19
22
8
10
14
70
60
50
99
95
90
S
S
S
16
16
24
40
45
25
89
91
85
S
S
S
(a) Absolute configuration was determined by specific rotation or by 1H NMR by preparing Mosher esters of the products.
(b) The specific activity of the enzyme carbonyl reductase present in (i) D. carota 245 mmol minꢀ1, mgꢀ1 protein (protein 15 lg/ml); (ii) yeast
465 mmol minꢀ1, mgꢀ1 protein (protein 25 lg/ml).
(c) Diastereoselectivity (trans/cis) ratio determined by GC/mass.
In summary, we have established an attractive, alternative,
simple and convenient procedure for the preparation of
both natural and unnatural secondary chiral alcohols
under mild and eco-friendly conditions.
NaOH/oxidation (IBX) gave the bromo substituted 2-inda-
nones. 7,8-Dimethoxy–2-tetralone 13c, was synthesized
according to the published procedure.18 Isopiperitenone
20 was obtained by allylic oxidation of limonene with
CrO3–pyridine complex. Compounds 13a, 13b, 15 and 17
and limonene were obtained from Aldrich Chemicals,
USA. Saccharomyces cerevisiae (baker’s yeast) Type II
was procured from Sigma Chemical Co., USA. D. carota
(carrot) was purchased from local super market, and the
carrot root cut into small graded pieces (approximately
4 mm long slices) for the study. Progress of the reduction
reactions was followed by TLC and HPLC using normal
phase column in a hexane/ethyl acetate (70:30) as a mobile
phase at 254 nm wavelength. The products obtained were
purified by silica gel (60–120 mesh) column chromatogra-
phy using hexane: ethyl acetate (analytical grade) solvent
system and the yields refer to purified homogeneous com-
pounds unless otherwise stated. The products were fully
characterized with specific rotation, mass, infrared spectra,
1H and 13C NMR spectra and the data obtained were used
4. Experimental
All the chemicals and solvents used are of analytical/spec-
tral grade obtained from commercial suppliers. Compound
4a was prepared as shown in Scheme 1. The treatment of
1-oximination of 2-indanone 3 with TMSCl and isoamyl
nitrite taken either neatly or in dichloromethane at
ꢀ20 ꢁC afforded 1-oximino-2-indanone 4a in 80% yield.
Compounds 4b–d and 7a were made according to the pub-
lished procedures.7,17 5-Bromo 2-indanone 9a was synthe-
sized from indane-2-ol acetate 8a with 1 equiv of NBS at
ꢀ25 ꢁC. Similarly, 5,6-dibromo 2-indanone 9b was pre-
pared from indane-2-ol acetate 8a with 2 equiv of NBS in
acetonitrile at 25 ꢁC and subsequent hydrolysis with

J. S. Yadav et al. / Tetrahedron: Asymmetry 18 (2007) 717–723
721
to compare to those reported in the literature. The diaste-
reomeric purity and enantiomeric excess of the chiral prod-
ucts obtained were determined either by GC/MS, 5%
phenyl methyl silicone 30 m · 0.25 mm · 0.25 m thickness,
carrier gas helium, or by HPLC using chiral column OD-
H Daicel column (0.46 · 25 cm OD) with a mobile phase,
hexane/isopropanol (85:15) at a wavelength of 254 nm.
The absolute configurations of the chiral molecules were
determined either by specific rotations or by the prepara-
NMR (75 MHz, DMSO-d6) d 40.12, 76.47, 125.05,
127.98, 128.41, 128.82, 129.42, 138.02, 152.64 (EI) m/z
163 (M+).
4.4. 7-Methyl (R)-2-hydroxy-1-indanone-oxime 5b
25
½aꢁD ¼ þ58:5 (c 0.7, MeOH). Solid mp 159–162 ꢁC. IR
(KBR): m 3231, 2882, 1621, 1469, 1452, 1329 cmꢀ1 1H
.
NMR (DMSO-d6): d 2.4 (s, 3H), 2.71 (dd, 1H, J = 2.5,
17.2 Hz), 3.34 (dd, 1H, J = 7.3, 17.4 Hz), 4.35 (br s, 1H,
OH), 4.50 (m, 1 H), 7.02–7.04 (m, 2H), 7.13 (dd, 1H,
J = 7.5, 7.2 Hz) 11.1 (s, 1H); 13C NMR (75 MHz,
DMSO-d6): d 22.4, 39.4, 79.0, 117.8, 124.7, 125.3, 126.9,
132.1, 138.56, 153.13; HRMS m/z calcd for C10H11NO2
(M+) 177.0790; found, 177.0793.
1
tion of Mosher esters (MTPH) of the products. H and
13C NMR spectra are recorded in CDCl3/DMSO solution
using Varian Gemini-200/400/75 MHz NMR spectro-
scopy. Mass and IR spectra were recorded using VG,
Micro mass 7070H and Nicolet-740, respectively. Optical
rotations were taken on Jasco Dip-360 digital polarimeter.
4.1. Daucus carota
4.5. 4-Methyl (R)-2-hydroxy-1-indanone-oxime 5c
25
Freshly cut D. carota root pieces (10 g) were suspended in
100 mL of 0.1 mM sodium phosphate buffer pH 6.5. To
this were added (200 mg) the ketones (indanones, tetral-
ones and monoterpenoids) in 500 mL conical flask. The
reaction was incubated in an orbital shaker (150 rpm) at
room temperature for different time intervals. The progress
of the reaction was monitored by TLC or by HPLC. On
obtaining the optimal product formation, the reaction
was terminated by filtering the carrot suspension and the
filtrate was extracted with organic solvent (ethyl acetate,
3 · 100 mL), the organic phase separated, dried and con-
centrated in vacuum at low temperature. The product in
the medium was extracted, purified and the chemical struc-
ture characterized. The specific activity of the dehydroge-
nase enzyme (enzyme known for reduction of ketones)
present in the homogenate was determined by spectropho-
tometrically measuring the oxidation of NAD (P) H at
340 nm at room temperature. The protein concentration
in the D. carota homogenate was measured by the Lowry
method.19
½aꢁD ¼ þ78:5 (c 0.9, MeOH). Solid mp 165–167 ꢁC. IR
(KBR): m 3321, 2961, 1629, 1465, 1424, 1001, 651 cmꢀ1
.
1H NMR (DMSO-d6): d 2.63 (s, 3H), 2.83 (dd, 1H,
J = 2.4, 17.3 Hz), 3.56 (dd, 1H, J = 7.5, 17.3 Hz), 4.42
(br s, 1H, OH), 4.62 (m, 1H), 7.05 (d, 1H, J = 7.2 Hz),
7.21–7.29 (m, 2H), 10.61 (s, 1H);
DMSO-d6): d 21.4, 38.4, 78.0, 119.8, 123.7, 127.1, 129.1,
133.9, 139.3, 152.7; HRMS m/z calcd for C10H11NO2
(M+) 177.0791; found, 177.0796.
13
C NMR (75 MHz,
4.6. 7-Isopropyl (R)-2-hydroxy-1-indanone-oxime 5d
25
½aꢁD ¼ þ23:5 (c 1, MeOH). Solid mp 204–206 ꢁC. IR
(KBR): m 3301, 2981, 1680, 1445, 1421, 1023, 750,
621 cmꢀ1
. d 1.27 (d, 3H,
1H NMR (DMSO-d6):
J = 6.6 Hz), 1.32 (d, 3H, J = 6.7 Hz), 2.71 (dd, 1H,
J = 15.6, 8.2 Hz), 3.17 (dd, 1H, J = 15.5, 7.7 Hz), 3.19–
3.27 (m, 1H), 4.28 (br s, 1 H, OH), 4.37–4.41 (m, 1H),
7.15 (d, 1H, J = 7.2 Hz), 7.29 (d, 1H, J = 7.8 Hz), 7.4
(dd, 1H, J = 7.5, 7.5 Hz), 10.92 (s, 1H); 13C NMR
(75 MHz, DMSO-d6): d 28.21, 31.9, 40.5, 79.8, 115.4,
119.1, 127.4, 129.2, 138.4, 139.9, 152.8; HRMS m/z calcd
for C12H15NO2 (M+) 205.1103; found, 205.1107.
4.2. Fermented yeast cells (Saccharomyces cerevisiae)
Lyophilized baker’s yeast (2 g) was incubated in a nutrient
medium containing sucrose (2 g), peptone (0.5 g), yeast ex-
tract (0.2 g) and MgCl2/ZnCl2 (0.1 g) dissolved in 0.1 mM
sodium phosphate buffer, pH 6.5 (200 mL), and incubated
at 28–37 ꢁC for 24 h. The fermented cells were treated with
allyl alcohol (20 mL), stirred for 3 h and later the solvent
was decanted. To the treated fermented yeast cells, the aro-
matic ketones (500 mg) were added and incubated in an
orbital shaker for their optimal product transformation.
The final products were purified by flash chromatography
and the structures confirmed by spectral data.
4.7. 5-Bromo (R)-2-hydroxy-1-indanone-oxime 11a
25
½aꢁD ¼ þ39:5 (c 0.6, MeOH). Solid mp 281–283 ꢁC. IR
(KBR): m 3300, 2989, 1645, 1445, 1433, 1049, 722 cmꢀ1
.
1H NMR (DMSO-d6): d 2.82 (dd, 1H, J = 16.3, 7.2 Hz),
3.23 (dd, 1H, J = 16.3, 6.1 Hz), 4.31 (br s, 1H, OH),
4.43–4.49 (m, 1H), 7.33 (s, 1H), 7.42 (d, 1H, J = 7.6 Hz),
13
7.57 (d, 1H, J = 7.6 Hz), 10.78 (s, 1H);
C NMR
(75 MHz, DMSO-d6): d 38.5, 77.4, 119.9, 123.4, 128.7,
129.9, 130.2, 139.1, 151.6; HRMS m/z calcd for
C9H8BrNO2 (M+) 240.9738; found, 240.9735.
4.3. (R)-2-Hydroxy-1-indanone-oxime 5a
4.8. 5,6-Di-bromo (R)-2-hydroxy-1-indanone-oxime 11b
25
½aꢁD ¼ þ48:2 (c 0.8, MeOH); compared with opposite iso-
25
25
mer values. lit.7b ½aꢁD ¼ ꢀ55:0 (c 1.0, MeOH). Solid mp
½aꢁD ¼ þ52:5 (c 0.9 MeOH). Solid mp 261–263 ꢁC. IR
148–149 ꢁC. IR (KBR): m 3220, 2900, 1604, 1461, 1428,
(KBR): m 3400, 2961, 2881, 1681, 1465, 1423, 1028,
1306, 1042, 976, 734 cmꢀ1. H NMR (DMSO-d6): d 2.80
633 cmꢀ1 1H NMR (DMSO-d6):
. d 2.63 (dd, 1H,
1
(dd, 1H, J = 2.6, 17.5 Hz), 3.22 (dd, 1H, J = 8.0,
17.5 Hz), 4.60 (br s, 1H, OH), 4.78 (m, 1H), 7.10–7.30
(m, 3H), 8.25 (d, 1H, J = 8.0 Hz), 10.80 (s, 1H); 13C
J = 16.4, 5.6 Hz), 3.25 (dd, 1H, J = 16.4, 5.9 Hz), 4.39
(br s, 1H, OH), 4.47–4.49 (m, 1H), 7.61 (s, 1H), 8.42 (s,
1H), 11.23 (s, 1H); 13C NMR (75 MHz, DMSO-d6): d

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J. S. Yadav et al. / Tetrahedron: Asymmetry 18 (2007) 717–723
37.2, 76.4, 118.9, 122.4, 129.7, 132.5, 134.2, 140.1, 158.6;
HRMS m/z calcd for C9H7Br2NO2 (M+) 318.8844; found,
318.8850.
4.14. 5,6-Dibromo-cis-1-amino-2-indanol 12f
Liquid: IR (KBr): m 3380, 1581, 1478, 1208, 1002 cmꢀ1; 1H
NMR (400 MHz, CDCl3): d 2.78 (dd, 1H, J = 16.0,
2.6 Hz), 3.8 (dd, 1H, J = 16.1, 5.6 Hz), 4.35 (d, 1H,
J = 5.7 Hz), 4.42 (ddd, 1H, J = 5.6, 5.4, 2.6 Hz), 7.32 (s,
1H), 7.45 (s, 1H). 13C NMR (75 MHz, CDCl3): d 38.63,
4.9. cis-1-Amino-2-indanol 6a
1
Liquid. IR (KBr): m 3363, 2963, 1494, 980 cmꢀ1; H NMR
(300 MHz, CDCl3): d 2.95 (dd, J = 3.0, 16.5 Hz for H1),
3.10 (J = 5.5, 16.5 Hz)0 4.30 (d, 1H, J = 5.5 Hz), 4.40 (m,
1H), 7.20–7.35 (m, 4H). 13C NMR (75 MHz, DMSO-d6):
d 39.45, 64.39, 75.76, 124.39, 126.65, 127.48, 127.92,
64.19, 77.17, 120.42, 122.38, 127.57, 130.29, 139.19,
25
140.15. EIMS: m/z: 308 (M++2), ½aꢁD ¼ ꢀ33:5 (c 1.5,
CHCl3).
138.39, 140.33. (EI) m/z = 149 M+. Optical rotation
4.15. 2-Tetralol 14a
25
½aꢁD ¼ þ56:6 (c 0.8, MeOH).
Liquid: IR (KBr): m 3450, 2922, 1609, 1008 cmꢀ1; 1H NMR
(300 MHz, CDCl3): d 1.74–1.88 (m, 1H), 2.01–2.12 (m,
2H), 2.79 (dd, 1H, J = 16.4, 7.9 Hz), 2.82–3.05 (m, 2H),
4.10. 7-Methyl-cis-1-amino-2-indanol 6b
Liquid: IR (KBr): m 3313–2561, 1592, 1470, 1092 cmꢀ1; 1H
NMR (400 MHz, CDCl3): d 2.21 (br s, 3H), 2.42 (s, 3H),
2.91 (dd, 1H, J = 15.7, 7.7 Hz), 3.17 (dd, 1H, J = 15.9,
7.3 Hz), 4.31 (d, 1H, J = 6.7 Hz), 4.41 (ddd, J = 7.2, 7.2,
7.2 Hz) 7.01–7.03 (m, 2H), 7.13 (dd, 1H, J = 7.7, 7.
4 Hz); 13C NMR (75 MHz, CDCl3): d 18.7, 39.2, 55.5,
71.1, 123.7, 128.57, 128.48, 134.4, 141.7, 143.5 EIMS:
3.12 (dd, 1H, J = 16.4, 5.2 Hz), 4.15–4.21 (m, 1H), 7.08–
25
7.18 (m, 4H). EIMS m/z: 148 M+, ½aꢁD ¼ ꢀ19:2 (c 0.9,
25
CHCl3) lit.11c ½aꢁD ¼ ꢀ20:8 (c 0.25, CHCl3).
4.16. 7-Methoxy-2-tetralol 14b
Liquid: IR (KBr): m 3422, 2928, 1639 cmꢀ1 1H NMR
;
25
25
m/z; 163 M+ ½aꢁD ¼ ꢀ112:2 (c 0.6, CHCl3). lit.18 ½aꢁD
¼
(300 MHz, CDCl3): d 1.64 (s, OH), 1.70–1.88 (m, 1H),
1.99–2.07 (m, 1H), 2.72–2.83 (m, 2H), 2.88 (dt, 1H,
J = 16.6, 5.8 Hz), 3.03 (dd, 1H, J = 16.3, 4.7 Hz), 3.77 (s,
3H), 4.08–4.19 (m, 1H) 6.62 (d, 1H, J = 2.7 Hz), 6.71
(dd, 1H, J = 8.5, 2.7 Hz), 7.05 (d, 1H, J = 8.5 Hz). EIMS:
ꢀ110:8 (c = 0.6, CHCl3).
4.11. 4-Methyl-cis-1-amino-2-indanol 6c
25
25
m/z: 178 M+, ½aꢁD ¼ þ16:1 (c 1.0, CHCl3). lit.11c ½aꢁD
¼
Liquid: IR (KBr): m 3342, 1602, 1480, 1325, 1020 cmꢀ1; 1H
NMR (400 MHz, CDCl3): d 2.25 (s, 3H), 2.71 (dd, 1H,
J = 16.5, 2.5 Hz), 3.0 (dd, 1H, J = 16.2, 5.5 Hz), 4.21 (d,
1H, J = 5.2 Hz), 4.31 (ddd, 1H, J = 5.5, 5.3, 2.5 Hz), 7.02
(d, 1H, J = 7.2 Hz), 7.23–7.25 (m, 2H); 13C NMR
þ16:3 (c 0.23, CHCl3).
4.17. 7,8-Dimethoxy-2-tetralol 14c
Liquid IR (KBr): m 3388, 2938, 1600 cmꢀ1 1H NMR
;
(75 MHz, CDCl3) d 19.1, 37.9, 59.1, 71.9, 122, 128, 128.6,
25
133.9, 140.1, 144.4. EIMS m/z: 163 M+ ½aꢁD ¼ ꢀ29:6 (c
25
(300 MHz, CDCl3): d 1.71–1.84 (m, 2H), 1.98–2.05 (m,
1H), 2.68 (dd, H, J = 18.0, 7.6 Hz), 2.77 (ddd, 1H,
J = 16.6, 8.9 and 5.8 Hz), 2.89 (dt, 1H, J = 16.5 and
5.7 Hz), 3.18 (dd, 1H, J = 17.1 and 5.7 Hz), 3.72 (s, 3H),
0.7, CHCl3). lit.18 ½aꢁD ¼ ꢀ30:7 (c 0.9, CHCl3).
4.12. 7-Isopropyl-cis-1-amino-2-indanol 6d
3.88 (s, 3H), 4.05–4.18 (m, 1H), 6.75 (d, 1H), 6.84 (d, 1H,
25
J = 8.6 Hz). EIMS: m/z: 208 M+ ½aꢁD ¼ þ19:1 (c 0.43,
25
Liquid: IR (KBr): m 3294, 1489, 1455, 1381, 1343,
CHCl3). lit.11c ½aꢁD ¼ þ18:1 (c = 0.41, CHCl3).
1
1090 cmꢀ1; H NMR (400 MHz, CDCl3): d 1.27 (d, 3H,
J = 6.7 Hz), 1.32 (d, 3H, J = 6.7 Hz), 2.32 (br s, 3H),
2.90 (dd, 1H, J = 15.7, 8.4 Hz), 3.12 (dd, 1H, J = 15.7,
7.6 Hz), 3.15–3.24 (m, 1H), 4.20 (br, d, 1H, J = 6.6 Hz),
4.36–4.38 (m, 1H), 7.05 (d, 1H, J = 7.5 Hz), 7.13 (d, 1H,
J = 7.6 Hz), 7.24 (dd, 1H, J = 7.6, 7.6 Hz). 13C NMR
(75 MHz, CDCl3): d 22.8, 24.1, 31.1, 39.2, 54.8, 70.0,
122.5, 123.8, 128.5, 139.5, 140.9, 145.6. EIMS m/z: 192
4.18. Neomenthol 16
Liquid IR (KBr): m 3381, 2952, 1082 cmꢀ1 1H NMR
;
(300 MHz, CDCl3): d, 0.81 (s, 3H), 1.21 (s, 3H), 1.34 (s,
3H), 2.49 (m, 1H), 2.52 (m, 1H), 2.70 (m, 1H), 3.12 (s,
25
OH). EI: m/z: 156 (M+). ½aꢁD ¼ ꢀ21:2 (c 0.2 CHCl3).13
25
25
(M+1). ½aꢁD ¼ ꢀ113:1 (c 0.5, CHCl3). lit.18 ½aꢁD ¼ ꢀ114:2
(c 0.5, CHCl3).
4.19. Sodihydrocarvone 18
Liquid IR (KBr): m 1681, 1708, 2980 cmꢀ1 1H NMR
;
(300 MHz, CDCl3): d 0.89 (s, 3H), 1.69 (s, 3H), 2.00 (m,
4.13. 5-Bromo-cis-1-amino-2-indanol 12a
Liquid: IR (KBr): m 3293, 1592, 1450, 1074 cmꢀ1; 1H NMR
(300 MHz, CDCl3): d 2.82 (dd, 1H, J = 16.1, 2.5 Hz), 3.11
(dd, 1H, J = 16.2, 5.5 Hz), 4.23 (d, 1H, J = 5.6 Hz), 4.45
(ddd, 1H, J = 5.7, 5.4, 2.7 Hz), 6.91 (d, 1H, J = 8.13),
7.65 (s, 1H), 7.72 (d, 1H, J = 8.1 Hz). 13C NMR
(75 MHz, CDCl3): d 37.63, 62.38, 76.74, 118.73, 122.88,
1H), 2.25 (m, 1H), 4.79 (m, 1H), 4.81 (m, 1H); EIMS:
25
m/z: 152 M+. ½aꢁD ¼ ꢀ34 (c 0.5, CHCl3).13
4.20. Neoisodihydrocarveol 19
Liquid; IR (KBr): m 3388, 1680, 2948 cmꢀ1 1H NMR
;
(300 MHz, CDCl3): d 0.87 (s, 3H), 1.70 (s, 3H), 1.81 (m,
125.12, 129.38, 137.30, 139.57. EIMS: m/z: 230 (M++2).
25
½aꢁD ¼ ꢀ32:1 (c 0.8, MeOH).
1H), 2.60 (m, 1H), 2.72 (m, 1H), 3.11 (s, OH), 4.75 (m,

J. S. Yadav et al. / Tetrahedron: Asymmetry 18 (2007) 717–723
723
25
1H), 4.78 (m, 1H). EIMS: m/z: 154 M+ ½aꢁD ¼ ꢀ18:1 (c 0.7,
5. (a) Baldassarre, F.; Bertoni, G.; Chiappe, C.; Marioni, F. J.
Mol. Catal. B: Enzym. 2000, 11, 55–58; (b) Maczka, W. K.;
Mironowicz, A. Tetrahedron: Asymmetry 2004, 15, 1965–
1967; (c) Baskar, B.; Ganesh, S.; Lokeswari, T. S.; Chadha,
A. J. Mol. Catal. B: Enzym. 2004, 27, 13–17; (d) Caron, D.;
Coughlan, A. P.; Simard, M.; Bernier, J.; Piche, Y.; Chen-
evert, R. Biotechnol. Lett. 2005, 27, 713–716; (e) Bruni, R.;
Fantin, G.; Maietti, S.; Medici, A.; Pedrini, P.; Sacchetti, G.
Tetrahedron: Asymmetry 2006, 17, 2287–2291; (f) Blanchard,
N.; Pierrevande, W. Org. Biomol. Chem. 2006, 4, 2348–2353;
(g) Utsukihara, T.; Watanabe, S.; Tomiyama, A.; Chai, W.;
Akira Horiuchi, C. J. Mol. Catal. B: Enzym. 2006, 41, 103–
109.
25
CHCl3). lit.13 ½aꢁD ¼ ꢀ20:0 (c 0.2 EtOH).
4.21. Isopiperitenol 21
Liquid. IR (KBr): m 3341, 2981, 1683 cmꢀ1 1H NMR
;
(300 MHz, CDCl3): d 156 (s, 3H), 1.78 (s, 3H), 2.60 (s,
OH), 2.34 (m, 1H), 4.83 (m, 1H), 5.17 (m, 1H), 5.73 (m,
25
1H). EIMS: m/z: 152 M+. ½aꢁD ¼ ꢀ41:1 (c 0.5, CHCl3).13
4.22. Isopulegol: liquid 22
IR (KBr): m 3341, 2981, 1650 cmꢀ1 1H NMR (300 MHz,
CDCl3): d 0.84 (s, 3H), 1.52 (s, 3H), 1.62 (m, 1H), 1.82
6. (a) Yadav, J. S.; Reddy, P. T.; Nanda, S.; Bhaskar Rao, A.
Tetrahedron: Asymmetry 2001, 12, 3381–3385; (b) Yadav, J.
S.; Nanda, S.; Reddy, P. T.; Bhaskar Rao, A. J. Org. Chem.
2002, 67, 3900–3903; (c) Yadav, J. S.; Nanda, S.; Reddy, P.
T.; Bhaskar Rao, A. US Patent 20040082043, 2004. ‘A novel
enzymatic process for enantioselective reduction of ketones
using Tuberous root of Daucus carota’.
(m, 1H), 2.40 (s, OH), 3.72 (s, 3H), 4.93 (m, 1H), 4.98
25
(m, 1H). EIMS m/z: 154 M+. ½aꢁD ¼ ꢀ22:1 (c 0.9, CHCl3)
25
lit.14 ½aꢁD ¼ ꢀ13:4 (c 1.0, CHCl3).
7. (a) Mohammad, A. H. A.; Nagendrappa, G. Tetrahedron
Lett. 2003, 44, 2753–2755; (b) Kajiro, H.; Mitamura, S.;
Mori, A.; Hiyama, T. Bull. Chem. Soc. Jpn. 1999, 72, 1093–
1100.
Acknowledgements
G.S.K.K. and K.V.R. thank CSIR, New Delhi, for the
award of research fellowship, A.D.K. is grateful to the
Director, IICT, Hyderabad, for the financial support.
8. (a) Didier, E.; Loubinoux, B.; Romos Tomobo, G. M.; Rish,
G. Tetrahedron 1991, 47, 4941–4958; (b) Gosh, A. K.;
Fidanze, S.; Senanayake, C. H. Synthesis 1998, 937–961.
9. (a) Simone, B. D.; Savoia, D.; Tagliavini, E.; Umani-Ronchi,
A. Tetrahedron: Asymmetry 1995, 6, 301–306; (b) Chartrain,
M.; Jackey, B., et al. J. Ferment. Bioeng. 1998, 86, 550–558.
10. (a) Didier, E.; Loubinoux, B.; Ramos Tombo, G. H.; Rihs,
G. Tetrahedron 1991, 47, 4941–4958; (b) Hong, Y.; Gao, Y.;
Nie, X.; Zepp, C. M. Tetrahedron Lett. 1994, 35, 6631–6634;
(c) Ghosh, A. K.; Onishi, M. J. Am. Chem. Soc. 1996, 118,
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