Easy access to various natural keto polyunsaturated fatty acids and their corresponding racemic alcohols

Article abstract of DOI:10.1016/S0009-3084(03)00087-2

Various optically active hydroxy derivatives of polyunsaturated fatty acids were easily oxidised to their corresponding keto derivatives using Dess-Martin periodinane. The reaction was run on the millimolar scale with good yields and without appreciable isomerisation of the surrounding double bonds. Reduction of these keto compounds to yield back the starting alcohols, but now as racemic mixtures, was also conducted using CeCl₃-NaBH ₄, once again without noticeable modification of the stereochemistry of the double bonds. These reactions proved the usefulness of the chemoenzymatic access to oxylipins through the use of lipoxygenases with various regiospecificity, combined with chemical transformations of the formed hydro(pero)xides.

Full text of DOI:10.1016/S0009-3084(03)00087-2

Chemistry and Physics of Lipids 125 (2003) 115–121
Easy access to various natural keto polyunsaturated fatty
acids and their corresponding racemic alcohols
Gilles Iacazio∗
Laboratoire de Bioinorganique Structurale, Case 432, UMR CNRS 6517 “Chimie, Biologie et Radicaux libres”,
Faculté des Sciences de St Jéroˆme, Marseille Cedex 20, France
Received 25 March 2003; received in revised form 12 May 2003; accepted 27 May 2003
Abstract
Various optically active hydroxy derivatives of polyunsaturated fatty acids were easily oxidised to their corresponding keto
derivatives using Dess-Martin periodinane. The reaction was run on the millimolar scale with good yields and without appreciable
isomerisation of the surrounding double bonds. Reduction of these keto compounds to yield back the starting alcohols, but now as
racemic mixtures, was also conducted using CeCl3–NaBH4, once again without noticeable modification of the stereochemistry
of the double bonds. These reactions proved the usefulness of the chemoenzymatic access to oxylipins through the use of
lipoxygenases with various regiospecificity, combined with chemical transformations of the formed hydro(pero)xides.
© 2003 Elsevier Ireland Ltd. All rights reserved.
Keywords: Dess-Martin periodinane; Oxylipin; CeCl3; Ketodiene; Soybean lipoxygenase; Barley seed lipoxygenase
1. Introduction
of Arabidopsis thalliana by Pseudomonas sy-
ringae. Infiltration of such compounds in the plant
causes both the expression of the gene coding
glutathion-S-transferase (GST 1) and cell death
(Vollenweider et al., 2000).
Recently, it has been shown (Vollenweider et al.,
2000) that ketodienoic fatty acids (9-KODE and
13-KODE) accumulate after wounding and infection
O
OH
OH
O
O
O
13-KODE
9-KODE
Abbreviations: 9-HODE, 9-hydroxy-10E,12Z-octadecadienoic
acid; 9-HOTE, 9-hydroxy-10E,12Z,15Z-octadecatrienoic acid;
(Me-) 13-HODE, 13-hydroxy-9Z,11E-octadecadienoic acid (me-
thyl ester); (Me-) 13-HOTE, 13-hydroxy-9Z,11E,15Z-octadecatri-
enoic acid (methyl ester); 9-KODE, 9-oxo-10E,12Z-octadeca-
dienoic acid; 9-KOTE, 9-oxo-10E,12Z,15Z-octadecatrienoic acid;
(Me-) 13-KODE, 13-oxo-9Z,11E-octadecadienoic acid (methyl es-
ter); (Me-) 13-KOTE, 13-oxo-9Z,11E,15Z-octadecatrienoic acid
(methyl ester); BSLOX, barley seed lipoxygenase; SBLOX, soy-
bean lipoxygenase
It has been known for a long time that various
metabolites of the so-called octadecanoid pathway,
involving lipoxygenase as a key enzyme, are of pri-
mary importance in plant physiology (Feussner and
Wasternack, 2002; Weber, 2002; Blée, 2002; Howe
and Schilmiller, 2002). Such products like jasmonates,
volatile aldehydes, fatty aldehydes and others are
both involved in response to environmental stress and
developmental cues. The role of ketodienes as well
∗
Tel.: +33-491282856; fax: +33-491983208.
E-mail address: gilles.iacazio@univ.u-3mrs.fr (G. Iacazio).
0009-3084/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/S0009-3084(03)00087-2

116
G. Iacazio / Chemistry and Physics of Lipids 125 (2003) 115–121
as their biosynthesis are important emerging areas in
plant physiology.
yield back the hydroxy derivatives as racemic mix-
tures (see Scheme 1). In each case the variation of
the stereochemistry of the conjugated dienic system
was analysed by HPLC.
In order to study the role of keto acids in plants,
a general synthetic method is required, applicable to
both linoleic and ␣-linolenic acids, on either positions
9 and 13 of these acids. A much important point is
the control of the stereochemistry of the two dou-
ble bonds conjugated to the keto functionality which
should be E,Z.
2. Experimental
2.1. General
We have developed recently a very simple chemo-
enzymatic synthesis of both 9- and 13-hydroxydienoic
derivatives of linoleic and ␣-linolenic acid, using
BSLOX for 9 oxygenation and SBLOX for 13 oxy-
genation, followed by triphenylphosphine reduction
of the formed hydroperoxides (Iacazio et al., 1990;
Martini et al., 1994; Martini et al., 1996; Martini
and Iacazio, 1997). Key points of these transforma-
tions were the high fatty acid concentration used (up
to 0.1 M), the high yield (∼80%, 1 g scale easily
accessible) and the proper control of both the stere-
ochemistry of the newly formed conjugated system
and the regioselectivity of the insertion of the hy-
dro(pero)xy functionality. This led to the synthesis
of 9-HODE, 13-HODE, 9-HOTE and 13-HOTE with
more than 95% isomeric purity and, although not rel-
evant here, with at least 98% enantiomeric excess (S
enantiomer). Based on these results it was therefore of
interest to look for an oxidation system, able to gen-
erate keto acids from these easily accessible hydroxy
acids, without affecting the stereochemistry of the
conjugated dienoic system of such natural products.
During the course of this study, Koch et al. reported
on the synthesis of 9-KOTE and 13-KOTE by the
chemo-enzymatic approach described above (Koch
et al., 2002). Lipoxygenation of ␣-linolenic acid was
conducted by either tomato lipoxygenase (9-oxy-
genation) or SBLOX (13-oxygenation) and after re-
duction of the formed hydroperoxides, the ketodienes
were obtained through oxidation of the allylic alcohols
by Bobitt’s reagent (Bobbit, 1998). The reaction was
conducted on either 23 mg of 13-HOTE or 8.7 mg of
9-HOTE affording, respectively 13.3 mg of 13-KOTE
(58% yield) and 6 mg of 9-KOTE (69% yield).
In this paper is reported, based on the same synthetic
scheme, the Dess-Martin periodinane oxidation of
9-HODE, 13-HODE, 9-HOTE and 13-HOTE either as
free acids or as methyl ester derivatives, and the subse-
quent reduction of the formed keto compounds to
Dichloromethane (Rectapur, Prolabo) was passed
through activated silica and stored on molecular sieves
prior to use. Methanol (RPE grade, Carlo Erba) was
used without purification. Dess-Martin periodinane
was purchased from Acros Organics as a 15 wt.%
solution in dichloromethane and used as received,
CeCl3·7H2O was from Lancaster and NaBH4 (98%)
from Aldrich. 1H (300 MHz) and 13C (75 MHz) NMR
spectra were run on a Bruker AC 300 spectrometer
in CDCl3 with TMS as internal standard. Chemi-
cal shifts are given in ppm (δ) downfield relative
to TMS. IR spectra were run on a Bruker IFS 25
spectrophotometer. UV spectra were recorded on a
Uvikon 943 double beam UV-Vis spectrophotometer.
Melting points were recorded on an Electrothermal
9300 apparatus and were uncorrected. Flash chro-
matography was performed on silica gel (Merck,
Kieselgel 60; 230–400 mesh). The stereoisomeric
distribution of either alcohol or keto fatty acids or
methyl esters were determined by HPLC (Kontron
HPLC pump 420) using a Waters Novapack Silica
(2 mm ×150 mm) column. The UV detector (Kontron
HPLC 335) was set at 234 nm for alcohols and 278 nm
for keto derivatives. The used eluents were 100/1/0.1
for alcohols and 100/0.4/0.2 for keto derivatives (hex-
ane/isopropanol/acetic acid) delivered, respectively at
0.7 and 0.8 ml/min.
2.2. General procedure for Dess-Martin
periodinane oxidation
In a 100 ml dry round bottom flask equipped with
a magnetic stirrer were weighted 1 mmol of hydroxy
fatty acids. Then 40 ml of dichloromethane were
added and the stirred mixture was cooled to 0 ◦C. Then
5 ml of Dess-Martin periodinane solution (1.7 equiv-
alent) were added. After 5 min at 0 ◦C the reaction
was completed (TLC analysis, solvent 70/30/0.2:

G. Iacazio / Chemistry and Physics of Lipids 125 (2003) 115–121
117
OH
OMe
O
O
rac 13-HODE
86 %
NaBH4-CeCl3
O
OH
OH
OH(OMe)
O
O
9-KODE
13-KODE
93 %
Dess-Martin periodinane
75 (85) %
OH
Dess-Martin periodinane
OH(OMe)
13S-HODE
OH
O
O
9S-HODE
SBLOX, O2
P(Ph)3
BSLOX, O2
P(Ph)3
O
OH
linoleic acid
O
OH
α-linolenic acid
SBLOX, O2
P(Ph)3
BSLOX, O2
P(Ph)3
OH
OH
OH(OMe)
OH
O
O
Dess-Martin periodinane
9S-HOTE
83 %
13S-HOTE
84 (92) %
Dess-Martin periodinane
O
OH
OH(OMe)
O
O
O
9-KOTE
13-KOTE
86 %
NaBH4-CeCl3
OH
OMe
O
rac 13-HOTE
Scheme 1. Chemo-enzymatic transformation of linoleic and ␣-linolenic acids.

118
G. Iacazio / Chemistry and Physics of Lipids 125 (2003) 115–121
pentane/diethyl ether/acetic acid). The reaction mix-
ture was then passed through a short pad of celite
and silica gel and eluted with a mixture of 70/30/0.2:
pentane/diethyl ether/acetic acid. After solvent evap-
oration the residue was purified using flash column
chromatography over silica (solvent 50/50/0.2: pen-
tane/diethyl ether/acetic acid). Fractions containing
the keto derivative were then pooled and evaporated
under vacuum. For methyl ester derivatives oxidation,
the same procedure was adopted, excepted that acetic
acid was omitted in solvent mixtures.
J = 6.8 Hz, 3H), 1.25–1.45 (m, 12H), 1.63 (m, 4H),
2.31 (m, 4H), 2.55 (t, J = 7.4 Hz, 2H), 5.90 (dt, J =
11.1, 7.8 Hz, 1H), 6.12 (t, J = 11.1 Hz, 1H), 6.18 (d,
J = 15.3 Hz, 1H), 7.49 (ddd, J = 15.3, 11.1, 0.6 Hz,
1H), 10.09 (br s, 1H), 13C NMR (75 MHz, CDCl3)
δ: 13.9, 22.4, 24.1, 24.6, 28.3, 28.9, 28.9, 29.0, 29.2,
31.5, 34.0, 41.2, 127.0, 129.4, 137.1, 142.5, 179.6,
201.4, IR (KBr, neat): 3450, 2925, 2850, 1694, 1618,
1588, 1468, 1409, 1265, 1220, 1192, 1077, 1000,
682 cm−1, UV (EtOH): λmax = 277.6 nm.
2.2.4. (9Z,11E,15Z)-13-Oxooctadecatrienoic acid
(13-KOTE)
2.2.1. (10E,12Z)-9-Oxooctadecadienoic acid
(9-KODE)
Yield: 84%, yellow viscous oil, 1H NMR (300 MHz,
CDCl3) δ: 0.99 (t, J = 7.6 Hz, 3H), 1.25–1.50 (m,
8H), 1.63 (m, 2H), 2.00–2.15 (m, 2H), 2.25–2.40 (m,
4H), 3.32 (d, J = 6.6 Hz, 2H), 5.58 (m, 2H), 5.92 (dt,
J = 11.1, 7.8 Hz), 6.12 (t, J = 11.1 Hz, 1H), 6.20 (d,
J = 15.3 Hz, 1H), 7.53 (ddd, J = 15.3, 11.1, 0.6 Hz,
1H), 9.34 (br s, 1H), 13C NMR (75 MHz, CDCl3) δ:
14.0, 20.9, 24.6, 28.3, 28.9, 29.0, 29.0, 29.2, 34.0,
41.1, 120.6, 126.9, 128.7, 135.3, 137.7, 142.9, 179.8,
198.8, IR (thin film): 2931, 2853, 1709, 1628, 1587,
Yield: 93%, cream amorphous solid, mp 49.5–
1
51.5 ◦C, H NMR (300 MHz, CDCl3) δ: 0.89 (t, J =
6.9 Hz, 3H), 1.33 (br s, 10H), 1.43 (m, 2H), 1.63 (m,
4H), 2.31 (t, J = 7.8 Hz, 2H), 2.34 (t, J = 7.3 Hz,
2H), 2.55 (t, J = 7.5 Hz, 2H), 5.91 (m, 1H), 6.12 (t,
J = 11.2 Hz, 1H), 6.17 (d, J = 15.3 Hz, 1H), 7.50
(ddd, J = 15.3, 11.2, 0.6 Hz, 1H), 10.09 (br s, 1H),
13C NMR (75 MHz, CDCl3) δ: 14.0, 22.5, 24.3, 24.6,
28.3, 28.9, 29.0, 29.1, 29.1, 31.4, 34.0, 41.0, 126.9,
129.3, 137.2, 142.8, 180.0, 201.2, IR (KBr, neat):
3450, 2925, 2853, 1694, 1625, 1593, 1470, 1410,
1311, 1255, 1230, 1118, 996, 717 cm−1, UV (EtOH):
λmax = 277.9 nm.
1461, 1412, 1276, 1189, 1091, 1069, 997, 725 cm−1
UV (EtOH): λmax = 279.9 nm.
,
2.2.5. (9Z,11E)-13-Oxooctadecatrienoic acid methyl
ester (Me 13-KODE)
1
2.2.2. (10E,12Z,15Z)-9-Oxooctadecatrienoic acid
(9-KOTE)
Yield: 85%, pale yellow oil, H NMR (300 MHz,
CDCl3) δ: 0.90 (t, J = 6.9 Hz, 3H), 1.25–1.50 (m,
12H), 1.55–1.70 (m, 4H), 2.25–2.35 (m, 4H), 2.55 (t,
J = 7.3 Hz, 2H), 3.66 (s, 3H), 5.89 (dt, J = 11.1,
7.8 Hz, 1H), 6.12 (t, J = 11.1 Hz, 1H), 6.17 (d, J =
15.3 Hz, 1H), 7.49 (ddd, J = 15.3, 11.1, 0.9 Hz, 1H),
13C NMR (75 MHz, CDCl3) δ: 13.9, 22.5, 24.1, 24.9,
28.3, 29.0, 29.0, 29.1, 29.3, 31.5, 34.1, 41.1, 51.5,
127.0, 129.4, 136.9, 142.4, 174.3, 201.1, IR (thin film):
2930, 2857, 1740, 1688, 1666, 1630, 1591, 1462,
1437, 1412, 1250, 1220, 1195, 1175, 1084, 1056, 997,
871, 727 cm−1, UV (EtOH): λmax = 277.3 nm.
Yield: 83%, pale yellow amorphous sticky solid,
mp 42.5–43.5 ◦C, 1H NMR (300 MHz, CDCl3) δ: 0.89
(t, J = 7.6 Hz, 3H), 1.34 (br s, 6H), 1.64 (m, 4H),
2.10 (m, 2H), 2.3 (t, J = 7.35 Hz, 2H), 2.56 (t, J =
7.4 Hz, 2H), 3.07 (t, J = 7.5 Hz, 2H), 5.25–5.55 (m,
2H), 5.86 (m, 1H), 6.14 (t, J = 11.3 Hz, 1H), 6.19
(d, J = 15.3 Hz, 1H), 7.53 (dd, J = 15.3, 11.3 Hz,
1H), 9.48 (br s, 1H), 13C NMR (75 MHz, CDCl3) δ:
14.2, 22.7, 24.3, 24.6, 26.6, 28.9, 29.1, 29.1, 34.0,
41.0, 125.3, 126.9, 129.7, 133.3, 136.8, 140.2, 180.0,
201.1, IR (KBr, neat): 3453, 2927, 2853, 1697, 1621,
1591, 1470, 1409, 1309, 1247, 1229, 1116, 1072, 996,
720 cm−1, UV (EtOH): λmax = 277.3 nm.
2.2.6. (9Z,11E,15Z)-13-Oxooctadecatrienoic acid
methyl ester (Me 13-KOTE)
Yield: 92%, yellow oil, 1H NMR (300 MHz,
CDCl3) δ: 0.99 (t, J = 7.5 Hz, 3H), 1.315 (br s,
6H), 1.36–1.47 (m, 2H), 1.62 (m, 2H), 2.09 (m, 2H),
2.25–2.36 (m, 4H), 3.31 (d, J = 6.3 Hz, 2H), 3.66
(br s, 3H), 5.58 (m, 2H), 5.91 (dt, J = 11.4, 7.8 Hz),
2.2.3. (9Z,11E)-13-Oxooctadecatrienoic acid
(13-KODE)
Yield: 75%, white amorphous sticky solid, mp
39.5–41.5 ◦C, 1H NMR (300 MHz, CDCl3) δ: 0.90 (t,

G. Iacazio / Chemistry and Physics of Lipids 125 (2003) 115–121
119
10.9, 1H), 13C NMR (75 MHz, CDCl3) δ: 14.1, 22.6,
24.9, 25.1, 27.7, 29.0, 29.1, 29.1, 29.5, 31.8, 34.1,
37.3, 51.5, 72.9, 125.7, 127.8, 132.8, 136.0, 174.4,
IR (thin film): 3426, 3005, 2920, 2856, 1738, 1462,
1436, 1362, 1247, 1198, 1084, 1019, 985, 950, 854,
726 cm−1, UV (EtOH): λmax = 231.9 nm.
6.12 (t, J = 11.4 Hz, 1H), 6.19 (d, J = 15.3 Hz, 1H),
7.53 (ddd, J = 15.3, 11.4, 0.9 Hz, 1H), 13C NMR
(75 MHz, CDCl3) δ: 14.0, 20.9, 24.9, 28.4, 29.0, 29.0,
29.1, 29.3, 34.0, 40.1, 120.6, 126.9, 128.7, 135.2,
137.5, 142.8, 174.2, 198.5, IR (thin film): 2932, 2856,
1738, 1688, 1665, 1624, 1590, 1461, 1437, 1412,
1266, 1196, 1174, 1090, 1069, 997, 851, 730 cm−1
,
UV (EtOH): λmax = 279.6 nm.
2.3.2. 13-hydroxy-9Z,11E,15Z-octadecatrienoic acid
methyl ester (Me 13-HOTE)
Yield: 86%, pale yellow oil, H NMR (300 MHz,
1
2.3. General procedure for NaBH4–CeCl3 mediated
reduction
CDCl3) δ: 0.97 (t, J = 7.5 Hz, 3H), 1.2–1.5 (m, 8H),
1.62 (m, 2H), 2.0–2.4 (m, 8H), 3.66 (s, 3H), 4.21 (dt,
J = 6.6, 6.6 Hz, 1H), 5.3–5.6 (m, 3H), 5.69 (dd, J =
15.3, 6.6 Hz, 1H), 5.97 (t, J = 11.0 Hz, 1H), 6.51
(dd, J = 15.3, 11.0, 1H), 13C NMR (75 MHz, CDCl3)
δ: 14.2, 20.8, 27.7, 29.0, 29.1, 29.1, 29.5, 34.1, 35.3,
51.5, 72.1, 123.8, 123.8, 125.8, 127.8, 132.8, 135.1,
174.3, IR (thin film): 3433, 3007, 2931, 2855, 1741,
1462, 1436, 1366, 1247, 1199, 1174, 1091, 1038, 985,
869, 732 cm−1, UV (EtOH): λmax = 233.9 nm.
In a 100 ml round bottom flask equipped with a
magnetic stirrer were weighted 0.9 mmol of keto
dienoic fatty acid methyl esters. Then 20 ml of
methanol was added and the stirred mixture was
cooled to 0 ◦C. Then 1 mmol of CeCl3·7H2O (1.1
equivalent) and NaBH4 (1.1 equivalent) were added.
After 5 min at 0 ◦C the reaction was completed (TLC
analysis, solvent 60/40: pentane/diethyl ether). The
reaction mixture was then passed through a short
pad of celite rinsed with methanol. After solvent
evaporation the oily residue was purified using flash
column chromatography over silica (solvent 60/40:
pentane/diethyl ether). Fractions containing the hy-
droxy derivatives were then pooled and evaporated
under vacuum.
3. Results and discussion
3.1. Oxidation with Dess-Martin periodinane
The following compounds, 13-HODE, 13-HOTE,
9-HODE, 9-HOTE, Me 13-HODE and Me 13-HOTE
were synthesised according to previously described
procedures with SBLOX for 13-hydroperoxides
and BSLOX for 9-hydroperoxides, followed by
triphenylphosphine reduction (Iacazio et al., 1990;
Martini et al., 1994; Martini et al., 1996; Martini and
Iacazio, 1997). For each compounds the oxidation
was conducted on the mmole scale (∼300 mg) with
1.7 equivalent of Dess-Martin periodinane in CH2Cl2
2.3.1. 13-hydroxy-9Z,11E-octadecadienoic acid
methyl ester (Me 13-HODE)
Yield: 86%, colourless oil, 1H NMR (300 MHz,
CDCl3) δ: 0.89 (t, J = 6.6 Hz, 3H), 1.25–1.70 (br m,
20H), 2.18 (dt, J = 6.9, 6.9 Hz, 2H), 2.30 (t, J =
7.5 Hz, 2H), 3.66 (s, 3H), 4.10–4.20 (m, 1H), 5.43 (dt,
J = 10.9, 7.8 Hz, 1H), 5.66 (dd, J = 15.3, 6.9 Hz,
1H), 5.97 (t, J = 10.9 Hz, 1H), 7.49 (dd, J = 15.3,
Table 1
Evolution of the stereoisomeric distribution of conjugated dienes after Dess-Martin periodinane oxidation and NaBH4–CeCl3 reduction
Stereochemistry of the
starting material (ZE/EE)
Stereochemistry of the products
obtained through DMPOa (ZE/EE)
Stereochemistry of the products obtained
through NaBH4 reduction (ZE/EE)
13-HODE (98/2)
13-HOTE (98/2)
9-HODE (97/3)
13-KODE (94/6)
13-KOTE (98/2)
9-KODE (94/6)
9-HOTE (98/2)
9-KOTE (96/4)
Me 13-HODE (98/2)
Me 13-HOTE (97/3)
Me 13-KODE (98/2)
Me 13-KOTE (97/3)
rac Me 13-HODE (98/2)
rac Me 13-HOTE (97/3)
a
DMPO: Dess-Martin periodinane oxidation.

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G. Iacazio / Chemistry and Physics of Lipids 125 (2003) 115–121
at 0 ◦C. The reaction was shown to be extremely rapid
(less than 5 min) and very clean (one spot to one spot
by TLC). Purification over silica by flash chromatog-
raphy afforded highly pure ketodienes in very good
yield (75–93%) and with very little isomerisation as
can be judged by HPLC (see Table 1). Structural de-
have been reported, by combining the use of lipoxy-
genases and Dess-Martin periodinane. The formed
keto acids have almost retained the stereochemistry of
their parent hydroxy compounds during the transfor-
mation. This reaction is insensitive to the number of
unsaturation and to the position of the alcohol func-
tionality and afforded, for the first time, multi-hundred
milligrams of these highly valuable natural com-
pounds. This transformation could also be coupled to
the reduction with CeCl3–NaBH4 for the synthesis of
racemic hydroxy fatty acids of fixed stereochemistry.
Such racemic compounds are valuable as standards
in chiral HPLC.
1
termination was conducted by H NMR, 13C NMR,
IR and UV spectroscopy and by comparison with
literature data (Koch et al., 2002; Kuklev et al., 1997).
The reaction proved to be versatile since applica-
ble to free fatty acids or their methyl esters, to dou-
bly or triply unsaturated fatty acids and whatever the
position of the hydroxy group. Thus, the combina-
tion of the well established chemoenzymatic synthesis
of hydroxy derivatives of PUFA’s with lipoxygenases
and the chemical oxidation of such compounds us-
ing Dess-Martin periodinane allowed the very easy
synthesis of a variety of ketodienes, relevant to plant
physiology, in high yields and on the multi-hundred
milligram scale.
Acknowledgements
The author is indebted to Dr. Bruno Faure for help-
ful discussions and for performing IR experiments.
References
3.2. Chemoselective reduction of Me 13-KODE and
Me 13-KOTE
Blée, E., 2002. Impact of phyto-oxylipins in plant defense. Trends
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With these results in hand, it was therefore of in-
terest also to study the reduction of the keto acids
back to the hydroxy parent acids as racemic mixtures.
Indeed almost all lipoxygenases are very enantiose-
lective catalysts and this is a case where the enan-
tiomerically nearly pure hydroxy acids are much more
easily accessible than their racemic counterparts. The
reducing system used was a NaBH4–CeCl3 mixture
(Gemal and Luche, 1981) developed for the chemos-
elective reduction of enones. The reaction was con-
ducted in MeOH at 0 ◦C allowing the synthesis of
racemic methyl 13-HODE and methyl 13-HOTE in
good yields (86%). Once again this transformation did
not changed noticeably the stereochemistry of the con-
jugated dienic system as can be judged by HPLC (see
Table 1). These compounds are valuable as standards
for chiral HPLC and could be of interest in physio-
logical studies.
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