A divergent synthesis of [1-14C]-mono-E isomers of fatty acids

Article abstract of DOI:10.1016/S0009-3084(03)00054-9

A convenient synthesis of [1-¹⁴C]-mono-trans fatty acid using olefin inversion as a key-step is described. This methodology allows for a facile synthesis of [1-¹⁴C]-labelled mono-trans analogues of oleic, linoleic and linolenic acids. As an example, only eleven steps were necessary to obtain the [1-¹⁴C]-mono-E isomers of linolenic acid from its commercial all-Z form. In the first step, Barton's decarboxylation procedure yielded a bromo intermediate. Epoxidation of this compound resulted in the formation of three monoepoxides, which could be separated by HPLC. After identification by ¹H NMR and MS, the pure monoepoxides were then subjected to inversion consisting of a stereospecific deoxygenation followed by a β-elimination step. Finally, the labelling was introduced by substitution of the bromine by a [¹⁴C]-cyano group followed by hydrolysis.

Full text of DOI:10.1016/S0009-3084(03)00054-9

Chemistry and Physics of Lipids 125 (2003) 83–91
Short communication
A divergent synthesis of [1-14C]-mono-E isomers of fatty acids
D. Georgin∗, F. Taran, C. Mioskowski
CEA/Saclay, DSV-DBJC-SMMCB-baˆt 547-Saclay-F-91191 Gif sur Yvette Cedex, France
Received 13 February 2003; received in revised form 7 April 2003; accepted 9 April 2003
Abstract
A convenient synthesis of [1-14C]-mono-trans fatty acid using olefin inversion as a key-step is described. This methodology
allows for a facile synthesis of [1-14C]-labelled mono-trans analogues of oleic, linoleic and linolenic acids. As an example, only
eleven steps were necessary to obtain the [1-14C]-mono-E isomers of linolenic acid from its commercial all-Z form. In the first
step, Barton’s decarboxylation procedure yielded a bromo intermediate. Epoxidation of this compound resulted in the formation
of three monoepoxides, which could be separated by HPLC. After identification by 1H NMR and MS, the pure monoepoxides
were then subjected to inversion consisting of a stereospecific deoxygenation followed by a ␤-elimination step. Finally, the
labelling was introduced by substitution of the bromine by a [14C]-cyano group followed by hydrolysis.
© 2003 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: [1-14C]-trans-fatty acid; Inversion of olefin; Barton’s bromodecarboxylation
1. Introduction
fatty acids isomers with the help of labelled com-
pounds. For this purpose many E fatty acids were
labelled in our laboratory with carbon-14 at the car-
boxylic position (Eynard et al., 1996; Berdeaux et al.,
1996). The in vivo biological results showed different
behaviours in the desaturation–elongation process as
well as in the oxidative metabolism (Bretillon et al.,
1998a,b) of the E isomers compared to their Z ana-
logues, highlighting the interest of such biological
studies. The main difficulty concerning the prepara-
tion of labelled E fatty acids was the synthesis of unla-
belled starting products which were not commercially
available. In the past, our synthetic strategy was based
on a step-by-step construction of each E isomer pre-
cursor using Wittig or copper-catalysed coupling re-
actions. This strategy is time consuming and involves
many steps for each isomer precursor preparation.
For example, thirteen steps were necessary to obtain
the [1-14C]-(9E,12Z,15Z)-octadecatrienoic acid.
All-Z polyunsaturated fatty acids such as linolenic
acid, linoleic and oleic acids are commonly found in
many vegetable oils (Zöllner, 1986). During the in-
dustrial process of edible oils production, i.e deodori-
sation or deep frying processes, E fatty acids are
formed (Ackman et al., 1974) as a result of heat treat-
ments (245–250 ◦C) (Grandgirard et al., 1984) or par-
tial hydrogenation steps (Ratnayake and Beare-Rogers,
1990). As a consequence, margarines, cooking oils and
fried products contain significant amounts, up to 10%,
of E polyunsaturated fatty acids (Wolff and Sebedio,
1991; Wolff, 1992). This finding has prompted re-
searchers to explore the in vivo metabolism of these
∗
Corresponding author. Tel.: +33-1-69-08-75-96;
fax: +33-1-69-08-79-91.
E-mail address: dominique.georgin@cea.fr (D. Georgin).
0009-3084/$ – see front matter © 2003 Elsevier Science Ireland Ltd. All rights reserved.
doi:10.1016/S0009-3084(03)00054-9

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D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
This communication describes a successful new ap-
2. Results and discussion
proach to this chemical problem and provides a con-
venient methodology for the divergent synthesis of ra-
diolabelled E fatty acids starting from natural all-Z
isomers.
A valuable route to introduce a carbon-14 into the
carboxylic position of fatty acids consists to syn-
thesise a bromo derivative, obtained by the Barton
Scheme 1. Principle of the divergent synthesis.
Scheme 2. Synthesis of the trans isomer of oleic acid.

D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
85
bromodecarboxylation reaction (Barton et al., 1983)
and to substitute the bromide atom by [14C]-potassium
cyanide followed by hydrolysis of the [14C]-cyano
group. Our main strategy, illustrated on Scheme 1,
was to prepare such bromo precursor from com-
mercially available all-Z fatty acids and to generate
a mixture of isomers which will be separated and
further functionalised. Oleic, linoleic and linolenic
acids present an increasing complexity of their struc-
ture and were chosen to establish the procedure. Our
synthetic route involved first to epoxidize the bromo
all-Z derivative with one equivalent of metachloroper-
benzoic acid (Imuta and Ziffer, 1979). After HPLC
chromatography separation, each monoepoxyde can
be submitted to stereospecific deoxygenation in order
to form the corresponding double bound. This is the
key-step which permits to reduce the length of the
synthetic pathway. However, we had to face three
difficulties. First, we had to set up a stereoselective
inversion procedure compatible with the terminal
bromine. Secondly, we had to establish a chromato-
graphic separation of each monoepoxides. Thirdly,
we had to elucidate each monoepoxide structure.
The first and main difficulty we had to face, was
the stereospecific deoxygenation of the epoxides to
the corresponding E olefins. Many reviews have con-
sidered the inversion of double bounds in olefins
(Sonnet, 1980; Wong et al., 1987). In order to eval-
uate the known procedures, we used oleic acid as
a reference compound. We studied some published
techniques (Mena et al., 1984; Dervan and Shippey,
1976; Rosenblum et al., 1975) but they were not
Scheme 3. Synthesis of mono-trans isomers of linoleic acid.

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D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
Scheme 4. Linoleic acid: differentiation of the epoxides.
compatible with the presence of a bromine on the
terminal carbon of the chain. Finally, we adapted
with success a high stereospecific method using triph-
enylphosphine dibromide and zinc (Sonnet and Oliver,
1976). The corresponding E bromo precursor was
obtained in 41% global yield with a stereochemical
purity greater than 99% (Scheme 2).
ozonolysis treatment (Pappas et al., 1966) followed
by mass spectrometry analysis (DCI/NH3) leading
to the following results: m/z: 224, 226 for epoxide 1
and 280, 282 for epoxide 2. These major peak corre-
sponded to the predicted molecular mass increased of
18 (+NH3). The elucidation of the structure of both
epoxides was therefore unambiguous.
The one-carbon homologation was then accom-
plished by reaction of this E bromoprecursor with
[1-14C] potassium cyanide in DMSO to give the ni-
trile derivative affording after hydrolysis, the [1-14C]
corresponding labelled E oleic acid in good yield.
Encouraged by this result, we evaluated the pro-
cedure for the synthesis of mono-E linoleic acids
isomers. After bromodecarboxylation of linoleic acid,
the bromoderivative was oxidised with one equivalent
of metachloroperbenzoic acid yielding a mixture of
two monoepoxides, starting materials and by-products
such as diepoxides. A flash chromatography was
therefore necessary to isolate both monoepoxides
which were successfully separated via a preparative
Zorbax Sil 21.2 mm i.d. × 25 cm HPLC column us-
ing a mixture of 2,2,4-trimethylpentane–petroleum
ether–diisopropyl ether (95–2.5–2.5) as eluant. Two
purified fractions were obtained and first named epox-
ide 1 and epoxide 2 according to their order of elution
(Schemes 3 and 4). Each fraction was subjected to an
These results validated our synthetic approach and
motivated us to go through a more difficult task. Ox-
idation of the bromo derivative of all-Z linolenic acid
generated three monoepoxides, first named epoxide
1, 2, 3 according to their elution order. We succeed
to identify them with the help of NMR spectrome-
try combined with an ozonolysis followed by mass
spectrometry analysis. Mass spectrometry of the
ozonolysis residues showed the following results:
m/z: 224–226 for epoxide 1; 224–226 for epoxide 2
and 280–282 for epoxide 3 (Scheme 5). We compared
these experimental results with the expected fragmen-
tations obtained from the three possible structures
(Scheme 6). Two structures should give the theoreti-
cal values m/z: 224, 226; and the third one 280, 282.
(Other fragments were too volatile to be observed.)
So, mass spectrometry was enough to determinate
the identity of epoxide 3. We investigate the structure
of epoxide 1 using its NMR spectrum which showed
a specific NMR signal (proton type 4, q.d, 2H) at

D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
87
Scheme 5. Synthesis of the mono-trans isomers of linolenic acid.
2.15–2.45 ppm. As only one structure presented this
feature, it was possible to assign the structure of epox-
ide 1. Furthermore, we identified epoxide 2, whose
NMR spectrum showed two characteristic type 3 pro-
tons (m) at 1.55 ppm. (the different types of protons are
described in Fig. 1.) As the ozonolysis-mass spectrum
method did not differentiate epoxide 1 and epoxide 2,
NMR spectrum was not enough to lift the ambiguity
between epoxide 2 and epoxide 3. The combination
of the two processes was necessary in this case.

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D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
Scheme 6. Linolenic acid: differentiation of the epoxides.
After the labelling step, confirmed the structure of
(9E, 12Z, 15Z)-[1-14C]-octadeca-9,12,15-trienoic acid
by coelution on a HP-23 cis/trans FAME gas chro-
matography column with an authentic sample obtained
previously through a total synthesis (Eynard et al.,
1994).
3. Conclusion
We carried out, via an efficient and concise proce-
dure, the stereospecific synthesis of mono-E fatty acid
isomers starting from all-Z isomer. Only eleven steps
were necessary to obtain the three mono-E isomers
of linolenic acid therefore showing the competitivity
of the methodology toward more classical approaches
(previous pathway afforded only one isomer in twelve
steps). We are therefore convinced that this approach
represents an advance and is of practical utility in the
area of labelled fatty acids synthesis. This procedure
Fig. 1. Types of protons present in 1H NMR(CDCl3) spectra.

D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
89
is applicable to a large variety of lipids allowing a
time-saving synthesis of their trans analogues.
6.8 Hz, 2H, –CH2–CH2–Br), 2.0–2.15 (m, 4H, proton
type 1), 2.80 (t, J = 5.8 Hz, 4H, proton type 2), 3.40 (t,
J = 6.8 Hz, 2H, –CH2–Br, 5.25–5.45 (m, 6H, olefinic
H). MS (DCI/NH3): m/z (%): 333 (15), 332[M+ +18]
(63), 331 (20), 330[M+ + 18] (87), 314[M+] (20),
313 (22), 312[M+] (26), 311 (18), 305 (34), 256 (40),
121 (15), 109 (21), 108 (100), 95 (40), 93 (20).
4. Experimental
A typical procedure for the inversion of a double
bond of linolenic acid is described.
4.2. 2-(7-Bromoheptyl)-3-(2Z,5Z)-octa-2,
5-dienyl-oxirane
4.1. (3Z,6Z,9Z)-17-Bromoheptadeca-3,6,9-triene
Oxalyl chloride (10 g, 78.8 mmol) was added to
a mixture of (9E,12Z,15Z)-octadeca-9,12,15-trienoic
acid (Aldrich Chemicals) (5 g, 17.95 mmol) in 40 ml
of dry toluene stirred under argon. The mixture was
stirred at room temperature for 15 h under an argon
atmosphere, concentrated under vacuum, and diluted
three times with 30 ml of dry toluene before concen-
tration to remove the oxalyl chloride residue, which
could be very harmful for the second part of the
reaction. The product was used without further purifi-
cation. 2-Mercaptopyridine-N-oxide, sodium salt hy-
drate (3.5 g, 23.4 mmol) and 4-dimethylaminopyridine
(244 mg, 2 mmol) were dried under vacuum overnight
and introduced with 75 ml of bromotrichloromethane
into a three-necked flask in an anhydrous glove box.
Under the ventilated hood the flask was fitted with a
reflux condenser and a system providing a slow flow
of argon. The slurry was stirred and heated under
reflux (105 ◦C).
A mixture of (3Z,6Z,9Z)-17-bromoheptadeca-3,6,9-
triene (2.55 g, 8.14 mmol), 20 ml of dichloromethane
and 20 ml of a saturated aqueous solution of
sodium hydrogen carbonate was stirred at 0 ◦C us-
ing an ice-bath. To this mixture was added meta-
chloroperbenzoic acid (2.10 g, 8.14 mmol, value
obtained after titration). The reaction mixture was
cooled all day at 0 ◦C and was allowed to warm to
room temperature overnight. The two layers were sep-
arated and the aqueous layer was extracted three times
with 20 ml of dichloromethane. The combined organic
layers were washed with a saturated aqueous solution
of sodium thiosulphate in order to reduce a probable
excess of metachloroperbenzoic acid. The organic
layer was then concentrated under vacuum. Flash chro-
matography on silica gel with hexane–ether (99–1)
afforded a purified mixture of 2-((Z)-10-bromo-
dec-2-enyl)-3-(Z)-pent-2-enyl oxirane (epoxide 1),
2-((2Z, 5Z)-13-bromotrideca-2,5-dienyl)-3-ethyl oxi-
rane (epoxide 2) and 2-(7-bromoheptyl)-3-(2Z,5Z)-oc-
ta-2,5-dienyl-oxirane (epoxide 3) (1.250 g, 3.80 mmol,
In an anhydrous glove box the raw acyl chloride
was diluted with 25 ml of bromotrichloromethane and
stored in a syringe. This mixture was added through a
septum to the reaction flask over 30 min. Bubbles and
an orange coloration were observed and the reaction
was stirred under reflux for 2 h.
yield
=
47%). A preparative HPLC separation
was conducted using a preparative silica col-
umn (21.2 mm i.d. × 25 cm) made of high per-
formance chromatographic Zorbax packings (av-
A brown product appeared as a side product of
the reaction. After cooling at room temperature the
reaction mixture was filtered in order to eliminate
the brown residue. The crude product was then con-
centrated under vacuum and flash chromatographed on
silicagel with heptane elution to give (3Z,6Z,9Z)-17-
erage particle diameter
=
8 ␮m). A mixture
of isooctane–diisopropyl ether–petroleum ether
(95–2.5–2.5) was used as eluant. The flow rate
was set at 15 ml/min. These conditions allowed
to load 50 mg of sample on the column and af-
forded 258 mg of isomer 1, 306 mg of isomer 2 and
302 mg of isomer 3. Yield after purification = 32%.
2-(7-bromoheptyl)-3-(2Z,5Z)-octa-2,5-dienyl-oxirane.
IR (film): υ = 3012 cm−1(m), 2962(s), 2930(s),
2856(s), 1461(m), 1382(w), 868(w) and 562(w).
1H NMR(CDCl3): δ = 0.95 (t, J = 7.5 Hz, 3H,
–CH2–CH3), 1.2–1.4 (m, 8H), 1.5 (m, 2H, proton
bromoheptadeca-3,6,9-triene
(2.71 g,
8.6 mmol,
yield = 48%). IR (film): υ = 3011 cm−1(s), 2963(s),
2930(s), 1652(w), 1460(m), 1395(w), 1252(m),
1067(w), 916(w), 793(w), 721(m), 648(w), 564(w).
1H NMR (300 MHz, CDCl3): δ = 0.95 (t, J = 7.5 Hz,
3H, –CH2–CH3), 1.30–1.40 (m, 8H), 1.85 (q, J =

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D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
type 3), 1.85 (q, J = 6.8 Hz, 2H, –CH2–CH2–Br),
2.05 (q, J = 7.3 Hz, 2H, proton type 1), 2.15–2.45
(m, 2H, proton type 4), 2.8 (t, J = 6.7, 2H, pro-
ton type 2), 2.95 (m, 2H, proton type 5), 3.40 (t,
J = 6.8 Hz, –CH2–Br), 5.25–5.55 (m, 4H, olefinic
H). MS (DCI/NH3): m/z (%): 349 (14), 348[M+ +18]
(87), 347 (24) 346[M+ + 18] (100), 331 (12), 329
(10), 313 (12), 311 (13), 123 (5).
1655(w), 1463(m), 1438(m), 1393(w), 1255(m),
1070(w), 967(m), 792(w), 723(m), 646(w), 564(w).
1H NMR(CDCl3): δ = 0.95 (t, J = 7.5 Hz, 3H,
–CH2–CH3), 1.2–1.45 (m, 8H), 1.85 (q, J = 7.1, 2H,
–CH2–CH2–Br), 1.9–2.10 (m, 4H, proton type 1),
2.70–2.85 (m, 4H, proton type 2), 3.40 (t, J = 6.8,
2H, –CH2–Br), 5.25–5.45 (m, 6H, olefinic H). MS
(DCI/NH3): m/z (%): 333 (25), 332[M+ + 18] (100),
331 (32), 330[M+ + 18] (100), 314[M+] (13), 313
(11), 312[M+] (15), 311 (6), 256 (16), 108 (21).
4.3. Erythro (3Z,6Z)-9,10,17-tribromoheptadeca-
3,6-diene
4.5. (9E,12Z,15Z)-[1-14C]-Octadeca-9,12,15-
trienenitrile
A mixture of 2-(7-bromoheptyl)-3-(2Z,5Z)-octa-2,
5-dienyl-oxirane (0.190 g, 0.58 mmol) in 5 ml of
toluene was added to triphenylphosphine dibro-
mide (0.244 g, 0.58 mmol) in 5 ml of toluene. The
mixture was vigorously stirred at room temper-
ature overnight, and the crude product was then
flash chromatographed on silica gel. The elution
with hexane–diethyl ether (99–1) afforded ery-
thro (3Z,6Z)-9,10,17-tribromo-heptadeca-3,6-diene
In a 25 ml-flask, 49 mg of (3Z,6Z,9E)-17-bromohe-
ptadeca-3,6,9-triene (0.15 mmol), 24 mg of 14C potas-
sium cyanide (55 mCi/mmol, 0.375 mmol, 20.6 mCi)
and 3 ml of dimethylsulphoxide were stirred for
20 min at 80 ◦C. Ten milliliter of water were added
and the aqueous layer was extracted three times with
20 ml diethyl ether. The mixture was dried under
vacuum and purified using flash chromatography
on silica gel with pentane–diethyl ether (95–5) as
eluant. The purified product was submitted to ra-
dioactive counting and mass spectrometry. 7.9 mCi
(55 mCi/mmol) (0.14 mmol) were obtained (96%
(0.178 g, 0.37 mmol, yield
=
64%). IR (film):
υ
=
3011 cm−1(m), 2931(s), 2857(s), 1458(m),
1433(m), 1217(w), 1148(w), 538(w) and 513(w).
1H NMR (CDCl3): δ = 0.95 (t, J = 7.5 Hz, 3H,
–CH2–CH3), 1.2–1.45 (m, 8H), 1.85 (q, J = 6.8, 2H,
–CH2–CH2–Br), 1.95–2.15 (m, 4H, protons type 1
and type 6), 2.70–2.85 (m, 4H, protons type 2 and
type7), 3.40 (t, J = 6.8 Hz, 2H, –CH2–Br), 5.25–5.5
(m, 6H, olefinic H + proton type 8). MS (DCI/NH3):
m/z (%): 494 (29), 493 (24), 492 (95), 491 (30), 490
(100), 489 (11), 488[M+ + 18] (32), 330 (20), 328
(12), 314 (21), 313 (92), 312 (28), 311 (95).
1
yield). H NMR(CDCl3): δ = 0.95 (t, J = 7.5 Hz,
3H, –CH2–CH3), 1.2–1.7 (m, 8H), 1.9–2.1 (m, 4H,
proton type 1), 2.35 (t, J = 7.1, 2H, –CH2–CN),
2.7–2.8 (m, 4H, proton type 2), 5.25–5.45 (m, 6H,
olefinic H). MS (DCI/NH3): m/z (%): 281 (6), 280
(33), 279[M+ + 18] (100), 278 (9), 277 (20).
4.6. (9E,12Z,15Z)-[1-14C]-Octadeca-9,12,15-
trienoic acid
4.4. (3Z,6Z,9E)-17-Bromoheptadeca-3,6,9-triene
A solution of erythro (3Z,6Z)-9,10,17-tribromohep-
tadeca-3,6-diene (0.109 g, 0.23 mmol) in N,N-dime-
thylformamide (2 ml) was added to an ice-cooled
slurry of activated zinc (0.109 mg), acetic acid (three
drops) and N,N-dimethylformamide (5 ml). Stirring
was continued at 0 ◦C for 2 h before the reaction
mixture was diluted with water and filtered. After ex-
traction with pentane and concentration in vacuum, a
flash chromatography on silica gel with pure heptane
afforded purified (3Z,6Z,9E)-17-bromoheptadeca-
3,6,9-triene (0.055 g, 0.17 mmol, yield = 76%). IR
(film): υ = 3012 cm−1(m), 2963(s), 2929(s), 2855(s),
In a 25 ml-flask, 7.9 mCi of (9E,12Z,15Z)-[1-14C]-
octadeca-9,12,15-trienenitrile: (0.14 mmol), 5 ml of
a 40% aqueous solution of potassium hydroxide
and 5 ml of absolute ethanol were stirred for 12 h at
85 ◦C. TLC control on silica gel with pentane–diethyl
ether–acetic acid (90–10–1) showed the end of the
reaction. The mixture was then acidified using 10 ml
5N hydrochloric acid and extracted with diethyl
ether. The purification by flash chromatography us-
ing the same system as the TLC afforded 6.85 mCi
of (9E,12Z,15Z)-[1-14C]-octadeca-9,12,15-trienoic
acid (55 mCi/mmol, 0.12 mmol, yield
=
89%).

D. Georgin et al. / Chemistry and Physics of Lipids 125 (2003) 83–91
91
1H NMR(CDCl3): δ = 0.95 (t, J = 7.5 Hz, 3H,
–CH2–CH3), 1.2–1.4 (m, 8H), 1.65 (q, J = 7.2, 2H,
–CH2–CH2–COOH), 1.9–2.1 (m, 4H, proton type 1),
2.35 (t, J = 7.4, 2H, –CH2–COOH), 3.7–2.8 (m, 4H,
proton type 2), 5.25–5.45 (m, 6H, olefinic H). MS
(DCI/NH3): m/z (%): 300 (5), 299 (32), 298[M+ +18]
(100), 297 (9), 296 (15).
isomers of linoleic and ␣-linolenic acids in perfused rat liver.
J. Lipid Res. 39, 2228–2236.
Bretillon, L., Chardigny, J.M., Sebedio, J.L., Poullain, D., Nöel,
J.P., Vatele, J.M., 1998b. Oxidative metabolism of [1-14C]
mono-trans isomers of linoleic and ␤-linolenic acids in the rat.
Biochimica et Biophysica Acta. 1390, 207–217.
Dervan, P.B., Shippey, M.A., 1976. Trimethylsilylpotassium.
Deoxygenation of epoxides with inversion of stereochemistry.
J. Am. Chem. Soc. 98, 1265–1267.
An aliquot of the corresponding methyl ester was
obtained using oxalyl chloride and absolute methanol.
Gas chromatography using a HP6890 GC system
coupled with a 5973 mass selective detector and
helium as carrier gas was used to compare with an
authentic sample by a coelution on a HP-23 cis/trans
FAME (60 m ×0.25 mm ×0.25 ␮m) capillary column
using the following isocratic conditions: tempera-
ture, 200 ◦C; injector temperature, 250 ◦C. A single
peak was detected: retention time; 11.09 min. All-Z
linolenic acid methyl ester was not detected: reten-
tion time; 11.24 min. Its stereochemical and chemical
purities were better than 99%.
Eynard, T., Vatele, J.M., Poullain, D., Nöel, J.P., Chardigny,
J.M., Sebedio, J.L., 1994. Synthesis of (9Z,12Z,15E)- and
(9E,15Z)-octadecatrienoic acids and their [1-14C]-radiolabelled
analogs. Chem. Phy. Lipids 74, 175–184.
Eynard, T., Vatele, J.M., Berdeaux, O., Poullain, D., Nöel,
J.P., 1996. Synthesis of (9Z,12E)-, (9E,12Z), -[1-14C]-linoleic
acid, (9Z,12Z,15E)-, (9E,15Z)-[1-14C]-linolenic acid and
(5Z,8Z,11Z,14E)-[1-14C]-arachidonic acid. Grassas y Aceites
47, 81–85.
Grandgirard, A., Sebedio, J.L., Fleury, J., 1984. Geometrical
isomerization of linolenic acid during heat treatment of
vegetable oils. J. Am. Oil Chem. Soc. 61, 1563–1568.
Imuta, M., Ziffer, H., 1979. Convenient method for the preparation
of reactive oxiranes by direct epoxidation. J. Org. Chem. 44,
1351–1352.
Mena, P.L., Pilet, O., Djerassi, C., 1984. Phospholipid studies
of marine organisms. 7. Stereospecific synthesis of (5Z,9Z)-,
(5Z,9E)-, (5E,9Z)-, and (5E,9E)-5,9-hexacosadienoic acid. J.
Org. Chem. 49, 3260–3264.
The other products were synthesised following a
similar procedure (yields are given under the corre-
sponding product on the path scheme).
Pappas, J.J., Keaveney, W.P., Gancher, E., Berger, M., 1966. A
new and convenient method for converting olefins to aldehydes.
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