Regio- and stereoselective reduction of trans-4-phenylbut-3-en-2-one using carrot, celeriac, and beetroot enzyme systems in an organic solvent

Article abstract of DOI:10.1016/j.tetlet.2013.09.041

(S)-trans-4-Phenylbut-3-en-2-ol has been obtained in excellent yields and with high enantiomeric excess in the reduction of trans-4-phenylbut-3-en-2-one using the comminuted roots of carrot (Daucus carota L.), celeriac (Apium graveolens L. var. rapaceum),

Full text of DOI:10.1016/j.tetlet.2013.09.041

Accepted Manuscript
Regio- and stereoselective reduction of trans-4-phenylbut-3-en-2-one using car‐
rot, celeriac and beetroot enzyme systems in an organic solvent
Ewa Majewska, Mariola Kozłowska
PII:
S0040-4039(13)01595-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.09.041
TETL 43541
Reference:
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Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
10 June 2013
22 August 2013
12 September 2013
Please cite this article as: Majewska, E., Kozłowska, M., Regio- and stereoselective reduction of trans-4-
phenylbut-3-en-2-one using carrot, celeriac and beetroot enzyme systems in an organic solvent, Tetrahedron
Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.09.041
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Graphical Abstract
Regio- and stereoselective reduction of trans-
Leave this area blank for abstract info.
4-phenylbut-3-en-2-one using carrot, celeriac
and beetroot enzyme systems in an organic
solvent
Ewa Majewska, Mariola Kozłowska
O
OH
Plant tissue
isooctane
(
S) alcohol
-

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Regio- and stereoselective reduction of trans-4-phenylbut-3-en-2-one using carrot,
celeriac and beetroot enzyme systems in an organic solvent
Ewa Majewska , Mariola Kozłowska
Department of Chemistry, Faculty of Food Sciences, Warsaw University of Life Sciences, Nowoursynowska 159 C, 02-776, Warsaw, Poland
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
(S)-trans-4-Phenylbut-3-en-2-ol has been obtained in excellent yields and with high
enantiomeric excess in the reduction of trans-4-phenylbut-3-en-2-one using the comminuted
roots of carrot (Daucus carota L.), celeriac (Apium graveolens L. var. rapaceum) and beetroot
(Beta vulgaris L. subsp. Vulgaris) in isooctane. This is the first report of this bioreduction with
plant tissue in an organic solvent.
Available online
Keywords:
trans-4-phenylbut-3-en-2-one
2009 Elsevier Ltd. All rights reserved.
(
S)-trans-4-phenylbut-3-en-2-ol
isooctane
plants
Chemical reactions using intact parts of miscellaneous plants
The enantiomeric allylic alcohols (S)-(-) and (R)-(+)-trans-4-
phenylbut-3-en-2-ol are frequently used as chiral building blocks
for numerous biologically active compounds, and they are used
as biocatalysts have received significant attention. This growing
interest is due to the wide biotechnological potential of
enzymatic reactions. Biocatalytic transformations using plants
7
for studies of reaction mechanisms. Therefore, it is desirable that
1
can be applied in bioreduction of ketones, enzymatic
both enantiomers of this chiral starting material are available in
high enantiomeric purity. Optically active trans-4-phenylbut-3-
en-2-ol may be obtained via the lipase-catalyzed
transesterification of (R, S)-trans-4-phenylbut-3-en-2-ol using
2
1c,3
lactonization, hydrolysis of esters,
compounds,
bioreduction of nitro
4
,5
4
and hydroxylation and oxidation reactions.
Usually, healthy roots of common vegetables, that can be
obtained in all seasons, are used. The application of comminuted
tissue of ripe vegetable roots in biotransformations has the
advantages of low cost and short reaction times of ca. 48 hours,
the procedure is very simple and represents an alternative to
Baker’s yeast owing to the easy availability of plants, the use of
water without a carbon source and the simple work-up because
no emulsion is formed.
8
7
vinyl acetate or dimethyl malonate as an acyl donor, or by
9
ruthenium- or enzyme-catalyzed asymmetric reduction of trans-
10
4-phenylbut-3-en-2-one. The lipase-catalyzed transesterification
of the racemic alcohol using isopropenyl acetate as an acyl donor
in toluene is an efficient method for the preparation of
11
enantiomerically pure (S)-alcohol, whereas the (R)-alcohol may
be obtained by lipase-catalyzed enantioselective hydrolysis of the
1
1
corresponding racemic acetate.
Enantiomerically pure allylic alcohols are an important class
of versatile building blocks for organic synthesis. They permit a
wide range of subsequent transformations, including carbon-
carbon bond formation reactions, in addition to numerous
possibilities for the manipulation and introduction of functional
groups, and they may serve as useful chiral auxiliaries in many
In this paper the regio- and stereoselective reduction of trans-
4-phenylbut-3-en-2-one with various plants is described as a
convenient and simple procedure for the gram-scale preparation
of (S)-trans-4-phenylbut-3-en-2-ol (Scheme 1) with high
enantiomeric excess.
6
stereoselective transformations.
———
Corresponding author. Tel.: +48-22593-7612; fax: +4822 59 37 635; e-mail: ewa_majewska@sggw.pl

2
Tetrahedron Letters
Whole cell biocatalysis in an organic solvent has a limitation
due to the toxic effect of the solvent on the enzyme activity. On
the other hand, organic solvents may absorb inside the cell
membrane leading to a change in membrane fluidity and ease in
substrate uptake resulting in activity retention.
O
OH
Plant tissue
isooctane
(
-
S) alcohol
Scheme 1.
The biotransformation of trans-4-phenylbut-3-en-2-one into
The bioreductions in isooctane in the presence of carrot
Daucus carota L.), celeriac (Apium graveolens L. var.
rapaceum) and beetroot (Beta vulgaris L. subsp. Vulgaris)
proceeded in good to excellent yields. The highest yield was
achieved with carrot (96%), and were lower with celeriac (78 %)
and beetroot (71%).
(
trans-4-phenylbut-3-en-2-ol using plant tissue, has already been
observed in the reaction catalyzed by the beans of Vigna
5
unguiculata. In this case, the double bond was mainly reduced,
resulting in the formation of 4-phenylbutan-2-one. The product
of the exclusive reduction of the C=O bond was observed in only
trace amounts (3%). On the other hand, reduction of
cinnamaldehyde with coconut juice occurred selectively at the
carbonyl group to yield the corresponding alcohol (84%) without
All the selected plants reduced trans-4-phenylbut-3-en-2-one
to (S)-trans-4-phenylbut-3-en-2-ol with high enantioselectivity
(Table 1). The reduction occurred only at the carbonyl group.
Bioreduction of the carbonyl group by carrot and celeriac enzyme
12
affecting the double bond.
1
systems is well documented and proceeds enantioselectivity,
Healthy and ripe roots of carrot (Daucus carota L.), celeriac
Apium graveolens L. var. rapaceum) and beetroot (Beta vulgaris
following Prelog’s rule, which results in the formation of (S)-
alcohols predominantly.
(
L. subsp. Vulgaris) were selected for this biotransformation.
These vegetables are accessible in all seasons and have the
advantage of low cost. The reaction procedure is very simple: to
a stirred suspension of comminuted plant tissue (330 g) in
isooctane (600 ml). trans-4-phenylbut-3-en-2-one (1.5 g) was
added at 25 ˚C. Aliquots were withdrawn periodically and the
progress of the reaction was monitored by means of TLC and
GC. After three days, we observed the maximum percentage
yield and the plant residue was filtered off. The organic phase
In conclusion, the regio- and stereoselective reduction of
trans-4-phenylbut-3-en-2-one with comminuted roots of the
popular vegetables such as carrot, celeriac and beetroot in
isooctane can be viewed as a further useful tool for organic
chemists by virtue of the simplicity. The encouraging results
obtained here may offer new possibilities for the reduction of
selected , -unsaturated carbonyl compounds that are insoluble in
water, as a critical step in a synthetic organic pathway,
specifically avoiding the use of non-sustainable, hydride reducing
agents.
was dried over MgSO
4
, the isooctane was evaporated and the
crude residue was purified by flash column chromatography. The
1
13
structure of the product was confirmed by H NMR and FT-IR.
The enantiomeric excesses of the products were determined by
measuring specific rotations and calculated as follows:
References and notes
ee (%) = ([α]observed / [ ]maximum) x 100
1
.
a) Baldassarre, F.; Bertoni, G.; Chiappe, C.; Marioni, F. J. Mol.
Catal B: Enzym. 2000, 11, 55-58; b) Bruni, R.; Fantin, G.; Medici,
A.; Pedrini, P.; Sacchetti, G. Tetrahedron Lett. 2002, 43, 3377-
The biotransformation of trans-4-phenylbut-3-en-2-one
was also carried out in polar solvents such as water and
acetonitrile (Table 1). A water-miscible organic solvent was
thought to aid in the solubility by the phenomenon of co-
solvency, however, water-immiscible organic solvents aid by
forming a biphasic reaction mixture. In the cases of water and
acetonitrile no reaction was observed, probably due to the
insolubility of the substrate in polar solvents.
3
379; c) Mączka, W. K.; Mironowicz, A. Tetrahedron:
Asymmetry 2002, 13, 2299-2302; d) Utsukihara, T.; Watanabe, S.;
Tomiyama, A.; Chai, W.; Horiuchi, C. A. J. Mol. Catal B: Enzym.
2
006, 41, 103-109; e) Cordell, G. A.; Lemos, T. L. G.; Monte, F.
J, Q.; de Mattos, M. C. J. Nat. Prod. 2007, 70, 478-492; f) Xie, B.;
Yang, Q.; Yuan, W. J. Mol. Catal B: Enzym. 2009, 61, 284-288 g)
Liu, X.; Pan, Z. G.; Xu, J. H.; Li, H. X. Chin. Chem. Lett. 2010,
2
1, 305-308; h) Liu, X.; Wang, Y.; Gao, H. Y.; Xu, J. H. Chin.
Chem. Lett. 2012, 23, 635-638; i) Zilinskas, A.; Sereikaite, J. J.
Mol. Catal B: Enzym. 2013, 90, 66-69.
Olejniczak, T.; Mironowicz, A.; Wawrzeńczyk, C. Bioorg. Chem.
2003, 31, 199-205.
Table 1. Reduction of trans-4-phenylbut-3-en-2-one with
plant tissue
2
.
a
3
.
a) Mączka, W. K.; Mironowicz, A. Z. Naturforsch. 2007, 62c,
3
97-402; b) Vandenberghe A., Markó, I. E.; Lucaccioni, F.; Lutts,
Plant
Solvent
S-Alcohol
S. Ind. Crops Prod. 2013, 42, 380-385.
b
4.
Andrade, L. H.; Utsunomiya, R. S.; Omori, A. T.; Porto, A. L. M.;
Comasseto, J. V. J. Mol. Catal B: Enzym. 2006, 38, 84-90.
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V.; de Mattos, M. C.; da Conceicão F. de Oliveira, M.; Lemos, T.
L. G.; Gotor, V. Tetrahedron: Asymmetry 2010, 21, 566-570.
Lumbroso, A.; Cooke, M. L.; Breit, B. Angew. Chem. Int. Ed.
Yield (%)
ee (%)
5
6
.
.
carrot
2
H O
-
-
-
carrot
MeCN
-
carrot
isooctane
96
-
>99
-
2
013, 52, 1890-1932.
celeriac
celeriac
celeriac
beetroot
beetroot
beetroot
a
H
2
O
7.
Fehr, C.; Galindo, J. Angew. Chem. Int. Ed. 2000, 39, 569-573.
Burgess, K.; Jennings, L. D. J. J. Am. Chem. Soc. 1991, 113,
8
.
MeCN
-
-
6
129-6139.
9
1
.
Noyori, R.; Ohkuma, T. Angew. Chem. Int. Ed. 2001, 40, 40-73.
isooctane
78
-
98
-
0. Hage, A.; Petra, D. G. I.; Field, J. A.; Schipper, D.; Wijnberg, J.
B. P. A.; Kamer, P. C. J.; Reek, J. N. H.; van Leeuwen, P. W. N.
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2, 1025-1034.
1. Ghanem, A.; Schuring, V. Tetrahedron: Asymmetry 2003, 14, 57-
2.
2
H O
MeCN
-
-
1
1
isooctane
71
72
6
12. Fonseca, A. M.; Monte, F. J. Q.; da Conceicão F. de Oliveira, M.;
de Mattos, M. C.; Cordell, G. A.; Braz-Filho, R.; Lemos, T. L.G.
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Reduction over 3 days.
a
Determined by GC analysis.
1
3. Analytical methods:

3
Gas chromatography – Shimadzu GC-17, capillary column: Inert
Cap WAX (30 m x 0.25 mm), flame ionisation detector temp. 250
˚
C, split injector temp 250 ˚C, column temp. 40 ˚C/ min, gradient
1
5 C/min to 230 ˚C, carrier gas: N at 1 ml/min, retention time
2
(
min): ketone 13.18, alcohol 14.59
(
S)-trans-4-phenylbut-3-en-2-ol:
1
3
H NMR (500 MHz, CDCl ): 7.23-7.39 (m, 5H, aromatic), 6.55 (d,
J = 15.5 Hz, 1H), 6.27 (dd, J = 15.5, 6.5 Hz, 1H), 4.50 (m, 1H),
2
.77 (s, 1H, OH), 1.38 (d, 3H, CH )
3
-1
2 2
FT-IR (CH Cl ): v = 3600 cm (OH)
2
0
Polarimetry ATAGO AP-300: carrot, (S)–alcohol > 99% ee: [ ]
D
20
–
19.8 (c 1, CHCl
3
), [lit. [ ]
D
-19.9 (c 1, CH
2
Cl
–19.52 (c 1, CHCl
–14.32 (c 1, CHCl
2
) >99% ee];
); beetroot,
20
celeriac, (S)–alcohol 98% ee: [ ]
D
3
20
(
S)–alcohol 72% ee: [ ]
D
3
)