Stereoselective synthesis of isomers of the naturally occurring 13-hydroxy-2,4,9-tetradecatrienoic acid. Part II [1]

Article abstract of DOI:10.1007/s00706-003-0097-y

The stereoselective syntheses of four unsaturated hydroxy fatty acids (13S,2E,4E,9E)-13-hydroxy-2,4,9-tetradecatrienoic acid, (13S,9Z,11E)-13-hydroxy- 9,11-tetradecadienoic acid, (13S,9E, 11E)-13-hydroxy-9,11-tetradecadienoic acid, and (13S,2E,4E,9E)-13-hydroxy-2,4,9,11-tetradecatrienoic acid, are described. Wittig reactions, regioselective oxidation of dialcohol 3, and diastereomerization were used. Springer-Verlag 2004.

Full text of DOI:10.1007/s00706-003-0097-y

Monatshefte f€ur Chemie 135, 447–459 (2004)
DOI 10.1007/s00706-003-0097-y
Stereoselective Synthesis of Isomers
of the Naturally Occurring 13-Hydroxy-
2,4,9-tetradecatrienoic Acid. Part II [1]
Antje Huefner1;ꢀ, Christa Hoeller1, and Gottfried Reznicek2
1
Institute of Pharmaceutical Chemistry and Pharmaceutical Technology,
University of Graz, A-8010 Graz, Austria
2
Institute of Pharmacognosy, University of Vienna, PharmaCenter Vienna,
A-1090 Wien, Austria
Received July 25, 2003; accepted August 5, 2003
Published online February 5, 2004 # Springer-Verlag 2004
Summary. The stereoselective syntheses of four unsaturated hydroxy fatty acids (13S,2E,4E,9E)-
13-hydroxy-2,4,9-tetradecatrienoic acid, (13S,9Z,11E)-13-hydroxy-9,11-tetradecadienoic acid, (13S,9E,
11E)-13-hydroxy-9,11-tetradecadienoic acid, and (13S,2E,4E,9E)-13-hydroxy-2,4,9,11-tetradecatrie-
noic acid, are described. Wittig reactions, regioselective oxidation of dialcohol 3, and diastereomeriza-
tion were used.
Keywords. Fatty acid; Aldehydes; Wittig Reaction; (Z,E)-Isomerization.
Introduction
Hydroxy fatty acids, like hydroxylated arachidonic or linoleic acid, have attracted
interest because they show very different biologic effects. Thus, e.g. (S,9E,11Z)-13-
hydroxy-9,11-octadecadienoic acid (1, 13-HODE) alters cell proliferation [2, 3],
cell adhesion [4], apoptosis [5], and inflammation [3].
Contrary to 13-HODE enamidonine, a lipopeptide with an (E,E,E)-13-
hydroxy-2,4,9-tetradecatrienoic acid connected with a cyclic tetrapeptide via an
enamide bridge, slows down the EGF induced proliferation of BALB fibroblasts
[6, 7].
To provide material for biological tests four derivatives of these hydroxy fatty
acids were synthesized. All of them possess a C14 skeleton with the OH-group in
position 13, but differ in number and position of the double bonds.
ꢀ
Corresponding author. E-mail: antje.huefner@uni-graz.at

448
A. Huefner et al.
Results and Discussions
(13S,2E,4E,9E)-Ethyl 13-hydroxy-2,4,9-tetradecatrienoate (7)
In an earlier work [1] we described the synthesis of (9S,5Z)-5-decen-1,9-diol (2)
and subsequently (13S,2E,4E,9Z)-ethyl 13-hydroxy-2,4,9-tetradecatrienoate. The
final selective diastereomerization of the conjugated double bonds was performed
by irradiation in presence of diphenyl disulfide. To prevent complete decomposi-
tion it was essential to filter the radiation with a 1% K2CrO4 solution. Like all later
depicted diastereomerizations, this reaction was monitored directly by 1H NMR in
benzene-d6 as solvent.
Irradiation of 2 with unfiltered UV light in the presence of diphenyl disulfide
afforded the equilibrium mixture of 2 and trans diol 3, and 3 was isolated by CC.
After oxidation of 3 to 4 the large (15.3 Hz) trans coupling constant between H-5
and H-6 proved the (E)-configuration. Wittig reaction with 3-ethoxycarbonyl-2-
propenyl-triphenylphosphonium bromide (5) and the final diasteromerization were
performed as reported in Ref. [1]. That way (see Scheme 1) 7 was synthesized in an
overall yield of 11% starting from 2.
(S)-13-Hydroxy-9,11-tetradecadienoic acids 14 and 17
These syntheses started with l-ethyl lactate as chiral synthon. The OH-group was
protected as its TBDMS ether [8] and the ester was reduced with DIBALH [9].
Scheme 1

Isomers of the 13-Hydroxy-2,4,9-tetradecatrienoic Acid
449
Resulting 8 afforded 10 after a Wittig reaction with formylmethylentriphenylphos-
phorane (9). If the reaction temperature was increased from room temp. [10] to
40ꢁC the reaction was finished after 20 h instead of 3 days with slightly decreased
yield. Ylide 9 was prepared in a modification of the methods of Refs. [11, 12] to
double the yield of Ref. [11] from 23 to 51%.
Phosphorous salt 12 was prepared in five steps from oleic acid with initial
methylation of the carboxyl function with MeOH, HC(OMe)3, and H2SO4. Ozo-
nolysis of methyl oleate [13], reduction with NaBH4 [14], and substitution of OH
versus Br with CBr4 and PPh3 [15] yielded methyl 9-bromononanoate. This was
converted to the salt 11. Using the method of Gerard and Patin [16] it was
essential that PPh3 was recrystallized from light petrol ether (PPh3 recrystallized
from ethanol did not work).
The next Wittig reaction was carried out similar to Ref. [16]. Using NaHMDS
as base instead of LiHMDS resulted in a product containing (9Z)- and (9E)-isomers
12 and 15 in a ratio of about 9:1. The (9Z,11E)-configuration of the main product
was confirmed by the small (10.6 Hz) cis coupling constant between H-9 and H-10
and the large trans (15.0 Hz) coupling constant between H-11 and H-12. Com-
pound 12 was saponified with LiOH [17] and desilylated with TBAF [8, 18] obtain-
ing unprotected acid 14 in an overall yield of 17% starting from 8. Liberation of the
alcohol function of 12 prior to the saponification resulted in complete decomposi-
tion of the intermediate methyl 13-hydroxy-9,11-tetradecadienoate.
Irradiation of 12 in the same procedure as used for the mixture of 5 and 6 yielded
the (E,E)-isomer 15 containing about 10% of educt 12. The large trans coupling
constants between H-9 and H-10 and betweeen H-11 and H-12 (both 14.9 Hz) in
1
the H NMR spectrum of 15 verify the (E,E)-configuration. Deprotection as
described for 12 gave 17 in an overall yield of 5% starting from 8.
Scheme 2

450
A. Huefner et al.
Scheme 3
(13S,2E,4E,9E,11E)-13-Hydroxy-2,4,9,11 tetradecatetraenoic acid (26)
A Wittig reaction similar to the method of Ref. [19] with 10 and phosphonium salt
18 resulted in a 3:2 mixture of the (5Z)-dienol 19 and the (5E)-isomer 20. In the 1H
NMR the coupling patterns of their olefinic protons compair to those of 12 and 15.
Though the isomers could be separated by CC we did later without because a
diastereomerization was planned as for 12. Aldehydes 21 and 22 were obtained
by oxidation with PCC [20] of 19 and 20. Coupling of 21 and 22 with 5 in a Wittig
reaction resulted in the four isomers of 23. This mixture was converted to the all-
trans isomer 24 similar to the irradiation of 12 or 6, yet the reaction time had to be
extended to 90 h. Deprotection as performed for 12 gave 26 in an overall yield of
4% starting from 8.
Experimental
Melting points: Melting point apparatus: Tottoli. Optical rotation: polarimeter 241 MC (Perkin
Elmer). MS: Varian MAT 711 spectrometer 70eV electron impact, GC=MS-Detector HP 6890
(MS: EI 70eV electron impact), Shimadzu QP 5050a, EI-MS, 70 eV. IR spectra: infrared spectrom-
eter System 2000 FT (Perkin Elmer). UV-Vis: UV-160A UV-visible recording spectrophotometer
(Shimadzu). NMR spectra: Varian Unity Inova 400 (297 K) 5 mm tubes, solvent resonance as
internal standard. 1H- and 13C-resonances were assigned using 1H,1H- and 1H,13C-correlation
spectra. Irradiation: high pressure mercury lamp Hanau-Hochdrucklampe TQ 150 Hg. Materials:
Column chromatography (CC) and filtration: silica: Kieselgel 60 (Merck) (70–230 mesh), pore-
˚
€
€
diameter 60A; alumina: Aluminiumoxid fur die Saulenchromatographie standardized, basic
pH¼ 10 ꢂ 0.5, Brockmann activity II, 0.05–0.15 mm (Fluka). Preparative thin-layer chromatogra-
phy (PLC): PLC plates (Merck) Kieselgel 60 F254, 1 mm, 200ꢃ200mm. Analytical thin-layer

Isomers of the 13-Hydroxy-2,4,9-tetradecatrienoic Acid
451
chromatography (TLC): TLC plates (Merck) Kieselgel 60 F254, 0.2mm, 200ꢃ200 mm; the deriv-
atives were detected in UV light at 254 nm and by spraying with molybdatophosphoric acid and
subsequent heating.
(9S,5E)-Decen-1,9-diol (3, C10H20O2)
First, 172 mg of 3 (1.00 mmol) and 437 mg of diphenyl disulfide (1.00 mmol) were dissolved in 8 cm3
of abs. benzene. Then the solution was filled into four 5 mm NMR tubes and Ar was bubbled through
for 5 min. The tubes were closed and placed in an irradiation apparatus and irradiated for 1.5h at room
temp. with a high pressure mercury lamp cooled with destilled H2O. The reaction mixture was
evaporated under reduced pressure. CC over 50g silica with EtOAc gave 90mg (52%) of 3 as a
colourless oil and 35mg of 2 (20%). Rf ¼ 0.35 (silica, EtOAc); 1H NMR (400MHz, CDCl3):
ꢀ ¼ 1.15 (d, J ¼ 6.1Hz, H-10), 1.39 (m, H-3), 1.46 (m, H-8), 1.52 (m, H-2), 1.81 (s br, OH), 1.98
(m, H-4), 2.05 (m, H-7), 3.58 (t, J ¼ 6.6 Hz, H-1), 3.77 (sext, J ¼ 6.2 Hz, H-9), 5.41 (m, H-5, 6) ppm;
13C NMR (100 MHz, CDCl3): ꢀ ¼ 23.3 (C-10), 25.6 (C-3), 28.9 (C-7), 32.1 and 32.2 (C-2, 4), 38.9 (C-
8), 62.7 (C-1), 67.7 (C-9), 130.1 and 130.5 (C-6, 5) ppm; IR (neat): ꢁꢀ¼ 3334 (s, br), 2964 (s), 2931 (s),
2859 (s), 1454 (m), 1374 (m), 1130 (m), 1067 (m), 969 (m), 733 (w) cmꢄ1; MS (70 eV): m=z
(%) ¼ 172 (Mþ, 1.0), 154 ((Mþ-H2O), 1.0), 139 (1.3), 136 (1.9), 121 (6.0), 107 (11.8), 95 (22.8),
23
93 (29.5), 81 (20.8), 79 (100), 67 (72.6), 45 (83.4); ½ꢂꢅD ¼ ꢄ7:1ꢁ cm2 gꢄ1 (c ¼ 0.35, CH2Cl2),
23
½ꢂꢅ546 ¼ ꢄ9:3ꢁ cm2 gꢄ1 (c ¼ 0.35, CH2Cl2).
(9S,5E)-9-Hydroxy-5-decenal (4, C10H18O2)
Under O2, 49mg of 3 (0.28 mmol), 9 mg of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)
(0.06 mmol), 83 mg of dry CuCl2 (0.62 mmol), and 35mg of CaH2 (0.82 mmol) in 2.2 cm3 of abs.
CH3CN were stirred vigorously in a 10 cm3 round bottom flask overnight. The reaction mixture was
evaporated under reduced pressure, diluted with 2 cm3 of H2O and extracted with 4ꢃ10cm3 of
CH2Cl2. The combined organic phases were washed with 2 cm3 of brine, dried over Na2SO4, and
evaporated. CC over 20 g of silica with EtOAc gave 20mg (43%) of 4 as a colourless oil. Rf ¼ 0.51
(silica, EtOAc); 1H NMR (400 MHz, CDCl3): ꢀ ¼ 1.15 (d, J ¼ 6.3Hz, H-10), 1.46 (m, H-8), 1.63 (s br,
OH), 1.65 (quint, J ¼ 7.4 Hz, H-3), 1.99 (m, H-4), 2.04 (m, H-7), 2.38 (td, J ¼ 7.3, 1.8 Hz, H-2), 3.75
(sext, J ¼ 6.3 Hz, H-9), 5.34 (dt, J ¼ 15.3, 6.1 Hz, H-5), 5.40 (dt, J ¼ 15.3, 6.2 Hz, H-6), 9.71 (t,
J ¼ 1.8 Hz, H-1) ppm; 13C NMR (100MHz, CDCl3): ꢀ ¼ 21.8 (C-3), 23.4 (C-10), 28.8 (C-7), 31.7
(C-4), 38.8 (C-8), 43.1 (C-2), 67.5 (C-9), 129.3 (C-5), 131.1 (C-6), 202.7 (C-1) ppm; IR (neat):
ꢁꢀ¼ 3419 (s), 2965 (s), 2931 (s), 2850 (s), 2722 (m), 1724 (s), 1452 (m), 1409 (m), 1392 (m), 1374
(m), 1130 (m), 1011 (m), 971 (m) cmꢄ1; MS (70 eV): m=z (%) ¼ 152 ((Mþ-H2O), 3.1), 137 (2.3), 123
23
(6.2), 108 (20.7), 93 (21.1), 79 (C6H7þ, 100), 67 (29.8), 55 (19.1), 31 (2.5); ½ꢂꢅD ¼ ꢄ10ꢁ cm2 gꢄ1
23
(c ¼ 0.49, CH2Cl2), ½ꢂꢅ546 ¼ ꢄ13ꢁ cm2 gꢄ1 (c ¼ 0.49, CH2Cl2).
(13S)-Ethyl 13-hydroxy-2,4,9-tetradecatrienoate
(mixture of (4Z)- and (4E)-isomer) (6 þ 7)
Under Ar, 242 mg of 5 (0.53 mmol) and 300 mg of K2CO3 in 10cm3 of abs. DMF were heated to
120ꢁC. A solution of 90mg of 4 (0.53 mmol) in 1 cm3 of abs. DMF was added and stirring at
120ꢁC was continued for 1.5 h. After cooling to room temp. the reaction mixture was poured into
20cm3 of H2O and extracted with 4ꢃ25 cm3 of Et2O. The combined extracts were washed with
20cm3 of brine, dried over Na2SO4, and evaporated under reduced pressure. CC over 50g of silica
with EtOAc gave 80 mg (57%) of the (Z=E)-mixture 6 þ 7 as a colourless oil. Rf ¼ 0.63 (silica,
EtOAc).

452
A. Huefner et al.
(13S,2E,4E,9E)-Ethyl 13-hydroxy-2,4,9-tetradecatrienoate (7, C16H26O3)
The (Z=E) mixture 6 þ 7 (80 mg, 0.30mmol) and 131 mg of diphenyl disulfide (0.60 mmol) were dis-
solved in 6 cm3 of abs. benzene. The solution was filled into three 5 mm NMR tubes and Ar was bubbled
through for 5 min. The tubes were closed and placed in an irradiation apparatus and irradiated for 14h at
room temp. witha high pressuremercurylampwitha 1%potassium chromatefilterina thicknessof1 cm.
The reaction mixture was evaporated under reduced pressure. CC over 10g of silica with EtOAc gave
55mg (69%) of 7 as a colourless oil. Rf ¼ 0.63 (silica, EtOAc); 1H NMR (400 MHz, CDCl3): ꢀ ¼ 1.13 (d,
J ¼ 6.3 Hz, H-4), 1.24 (t, J ¼ 7.2Hz, OCH2CH3), 1.44 (m, H-7, 12), 1.82 (s br, OH), 1.95 (m, H-8), 2.03
(m, H-11), 2.11 (quint, J ¼ 6.9 Hz, H-6), 3.84 (sext, J ¼ 6.2Hz, H-13), 4.15 (q, J ¼ 7.2 Hz, OCH2CH3),
5.37 (m, H-9, 10), 5.73 (d, J ¼ 15.3Hz, H-2), 6.04 (m, H-5), 6.12 (m, H-4), 7.20 (dd, J ¼ 15.4, 9.8 Hz, H-
3) ppm; 13C NMR (100 MHz, CDCl3): ꢀ ¼ 14.2 (OCH2CH3), 23.5 (C-14), 28.9 (C-11), 31.9 (C-8), 28.4
(C-7), 32.3 (C-6), 38.8 (C-12), 60.1 (OCH2CH3), 67.5 (C-13), 119.1 (C-2), 128.5, 129.9, and 130.4 (C-4,
9, 10), 144.2 (C-5), 144.9 (C-3), 167.2 (C-1) ppm; IR (neat): ꢁꢀ¼ 3430 (m, br), 2966 (s), 2929 (s), 2856
(m), 1714 (s), 1642(s), 1617(m), 1447 (m), 1393(m), 1369 (s), 1304(s), 1264 (s), 1247(s), 1137 (s), 1095
(m), 1039 (s), 1001 (s), 872 (w), 714 (w) cmꢄ1; UV-Vis (CH2Cl2, c ¼ 0.90ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax
(") ¼ 260.5 (19200) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 266 (Mþ, 1.6), 248 (4.0), 220
(9.8), 192 (7.0), 175 (10.3), 147 (14.0), 135 (22.2), 119 (28.1), 79 (C6H7þ, 100), 31 (7.8);
23
23
½ꢂꢅD ¼ ꢄ6:8ꢁ cm2 gꢄ1 (c ¼ 0.26, CH2Cl2); ½ꢂꢅ546 ¼ ꢄ8:4ꢁ cm2 gꢄ1 (c ¼ 0.26, CH2Cl2).
Formylmethylentriphenylphosphorane (9)
CHCl3 (750cm3) was added to 67.5g of a 50% aqueous solution of chloroethanal (0.39 mol). The
CHCl3=H2O-azeotrope (bp 56ꢁC) was destilled over a Raschig column. After destillation of about
400 cm3 of the azeotrope, 102.3 g of PPh3 (0.39 mol) were added to the yellow solution and the mixture
was refluxed for 5 h. The solvent was evaporated under reduced pressure, the residual phosphonium
salt was dissolved in 400 cm3 of H2O, and the organic phases were separated and discarded. After
addition of activated charcoal the mixture was stirred for 30 min at room temp. and filtered. Under
vigrous stirring 250 cm3 of 2 N NaOH solution were added dropwise to the filtrate and stirring was
continued for another hour. The product was filtered with suction, washed with 20cm3 of cold H2O, air
dried, suspended in 200 cm3 of acetone and stirred for 2 h at room temp. Filtration and drying over
P2O5 gained 60.7 g (51%) of 9 as an ocher powder. Mp 180–181ꢁC (Ref. [12] 186–187ꢁC).
(4S,2E)-4-tert-Butyldimethylsilyloxy-2-pentenal (10)
Aldehyde 8 (824 mg, 4.38 mmol) and 1.60g of ylide 9 (5.26 mmol) were stirred in 30 cm3 of abs.
benzene at 40ꢁC under Ar for 20 h before benzene was evaporated under reduced pressure. CC over
1
100 g of silica with cyclohexane:EtOAc¼ 9:1 afforded 675mg (72%) of 10 as a colourless oil. H
NMR signals of H-1, 2, 3, and 4 were found to be identical with those described in Ref. [21].
1H NMR (400 MHz, CDCl3): ꢀ ¼ 0.03 and 0.05 (s, Si(CH3)2), 0.88 (s, C(CH3)3), 1.28 (d,
J ¼ 6.6 Hz, H-5), 4.55 (m, H-4), 6.25 (ddd, J ¼ 14.8, 8.0, 1.5 Hz, H-2), 6.75 (dd, J ¼ 15.4, 4.0Hz,
H-3), 9.55 (d, J ¼ 8.1Hz, H-1) ppm; 13C NMR (100MHz, CDCl3): ꢀ ¼ ꢄ5:2 and ꢄ5.0 (Si(CH3)2),
18.1 (C(CH3)3), 23.3 (C-5), 25.7 (C(CH3)3), 67.7 (C-4), 129.8 (C-2), 160.9 (C-3), 193.7 (C-1) ppm.
Methyl oleate
Trimethyl orthoformiat (26.5 g, 0.25 mol) and 5 drops of conc. H2SO4 were added to a solution of
28.3g of oleic acid (0.10 mol) in 50cm3 of MeOH. The mixture was stirred over night at room temp.,
evaporated, the residue was diluted with 300 cm3 of Et2O, washed with 2ꢃ100 cm3 of 1 N NaHCO3
solution and 2ꢃ100 cm3 of H2O and dried over Na2SO4. Evaporation under reduced pressure yielded
28.5g (96%) of methyl oleate. The 1H NMR spectrum was found to be identical with that of Ref. [22].

Isomers of the 13-Hydroxy-2,4,9-tetradecatrienoic Acid
453
(13S,9Z,11E)-Methyl 13-tert-butyldimethylsilyloxy-9,11-tetradecadienoate (12, C21H40O3Si)
To a solution of 1.50g of salt 11 (2.92 mmol) in 25 cm3 of abs. THF at ꢄ78ꢁC under Ar 3.4 cm3
of a 1 N solution of NaHMDS in THF (3.4 mmol) were added and the mixture was stirred for
45min. After addition of 7.7 cm3 of HMPA and stirring for 2 min a solution of 419mg of 10
(1.95 mmol) in 5 cm3 of abs. THF were added and stirring was continued for further 45min. The
reaction was quenched by the addition of 38cm3 of warm (45ꢁC) H2O, the cooling bath was
removed, and the mixture was warmed up to room temp., stirred for further 30min, and extracted
with 3ꢃ100 cm3 of light petrol ether. The combined organic phases were washed with 80 cm3 of
brine, dried over Na2SO4, and evaporated under reduced pressure. CC over 50 g of silica with
cyclohexane:EtOAc¼ 9:1 afforded 370 mg (34%) of 12 as a colourless oil. Rf ¼ 0.45 (silica,
cyclohexane:EtOAc¼ 9:1); 1H NMR (400MHz, CDCl3): ꢀ ¼ 2ꢃ0.03 (s, Si(CH3)2), 0.88 (s,
C(CH3)3), 1.20 (d, J ¼ 6.2 Hz, H-14), 1.28 (m, H-4, 5, 6), 1.34 (quint, J ¼ 6.3Hz, H-7), 1.59
(quint, J ¼ 7.1 Hz, H-3), 2.13 (q, J ¼ 7.2 Hz, H-8), 2.28 (t, J ¼ 7.5 Hz, H-2), 3.66 (s, OCH3),
4.17 (quint, J ¼ 6.2 Hz, H-13), 5.37 (dt, J ¼ 10.6, 7.7 Hz, H-9), 5.63 (dd, J ¼ 15.0, 5.1 Hz, H-
12), 5.94 (t, J ¼ 11.0Hz, H-10), 6.42 (dd, J ¼ 15.0, 11.4Hz, H-11) ppm; 13C NMR (100 MHz,
CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.7 (Si(CH3)2), 18.3 (C(CH3)3), 24.5 (C-14), 24.9 (C-3), 25.9 (C(CH3)3),
27.7 (C-8), 29.0 and 2ꢃ29.1 (C-4, 5, 6), 29.6 (C-7), 34.1 (C-2), 51.4 (OCH3), 68.9 (C-13), 123.4
(C-11), 128.0 (C-10), 131.7 (C-9), 137.7 (C-12), 174.3 (C-1) ppm; IR (neat): ꢁꢀ¼ 2952 (s), 2929
(s), 2857 (m), 1773 (s), 1617 (m), 1472 (m), 1463 (m), 1436 (m), 1362 (m), 1255 (s), 1196 (m),
1168 (m), 1142 (m), 1092 (m), 988 (m), 836 (s), 776 (m) cmꢄ1
; UV-Vis (CH2Cl2,
c ¼ 1.1 ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 272.5 (2090), 236.5 (18400) nm; MS (70 eV): m=z
(%) ¼ 368 (Mþ, 3.0), 353 ((Mþ-Me), 0.1), 321 (1.0), 311 ((Mþ-C4H9), 8.1), 279 ((311-CH4O),
9.2), 237 ((Mþ-OTBDMS), 0.9), 211 (3.9), 187 (2.9), 159 (4.1), 144 (4.1), 131 (4.2), 117 (9.2), 115
25
(7.8), 104 (9.2), 93 (15.1), 75 ((Me2Si¼OH)þ, 100), 73 (37.0), 57 (26.5); ½ꢂꢅD ¼ þ18ꢁ cm2 gꢄ1
25
(c ¼ 0.092, CH2Cl2); ½ꢂꢅ546 ¼ þ16ꢁ cm2 gꢄ1 (c ¼ 0.092, CH2Cl2).
(13S,9Z,11E)-13-tert-Butyldimethylsilyloxy-9,11-tetradecadienoic acid (13, C20H38O3Si)
A solution of 252 mg of LiOHꢃ H2O (6.00 mmol) in 3 cm3 of H2O was added to 220 mg of 12
(0.597 mmol) in 6 cm3 of THF. The mixture was stirred under reflux and Ar for 14h, cooled to
room temp., poured into 20cm3 of 2 N H2SO4, and extracted with 3ꢃ30cm3 of Et2O. The
combined organic phases were washed with 10 cm3 of 2 N H2SO4 and 10cm3 of brine, dried over
Na2SO4, and evaporated under reduced pressure. CC over 40g of silica with
cyclohexane:EtOAc:AcOH¼ 69:31:4 afforded 182 mg (86%) of 13 as a colourless oil. Rf ¼ 0.44
(silica, cyclohexane:EtOAc: AcOH¼ 69:31:4); 1H NMR (400MHz, CDCl3): ꢀ ¼ 2ꢃ0.04 (s,
Si(CH3)2, 0.88 (s, C(CH3)3), 1.21 (d, J ¼ 6.2 Hz, H-14), 1.29 (m, H-4, 5, 6), 1.33 (m, H-7),
1.59 (quint, J ¼ 6.8 Hz, H-3), 2.13 (q, J ¼ 7.4Hz, H-8), 2.32 (t, J ¼ 7.5 Hz, H-2), 4.35 (quint,
J ¼ 6.0 Hz, H-13), 5.37 (dt, J ¼ 10.3, 7.8 Hz, H-9), 5.63 (dd, J ¼ 15.0, 5.1Hz, H-12), 5.94 (t,
J ¼ 11.0Hz, H-10), 6.42 (dd, J ¼ 15.0, 11.4 Hz, H-11), 10.2 (s, br, OH) ppm; 13C NMR
(100 MHz, CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.6 (Si(CH3)2), 18.3 (C(CH3)3), 24.5 (C-14), 24.6 (C-3),
25.9 (C(CH3)3), 27.6 (C-8), 2ꢃ29.0 and 29.1 (C-4, 5, 6), 29.6 (C-7), 34.1 (C-2), 69.0 (C-13),
123.4 (C-11), 128.1 (C-10), 131.7 (C-9), 137.7 (C-12), 180.1 (C-1) ppm; IR (neat): ꢁꢀ¼ 3008 (m),
2929 (s), 2857 (m), 2677 (m, br), 1712 (s), 1608 (w), 1471 (m), 1463 (m), 1442 (m), 1412 (m),
1362 (m), 1289 (m), 1255 (s), 1142 (m), 1092 (m), 1049 (m), 986 (m), 836 (s), 776 (m) cmꢄ1
;
UV-Vis (CH2Cl2, c ¼ 1.34 ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 237.5 (17000) nm (molꢄ1 dm3 cmꢄ1);
MS (70 eV): m=z (%) ¼ 354 (Mþ, 21.4), 339 ((Mþ-Me), 1.4), 321 ((339-H2O), 7.6), 297 ((Mþ-
C4H9), 13.8), 279 ((297-H2O), 68.0), 253 (3.2), 239 (7.8), 222 (14.0), 211 (13.1), 187 (21.8),
131 (18.8), 117 (38.5), 95 (47.4), 81 (64.0), 79 (45.5), 75 ((Me2Si¼OH)þ, 100), 73
22
22
(76.3), 55 (32.7); ½ꢂꢅD ¼ þ14ꢁ cm2 gꢄ1 (c ¼ 0.20, CH2Cl2); ½ꢂꢅ546 ¼ þ11ꢁ cm2 gꢄ1 (c ¼ 0.20,
CH2Cl2).

454
A. Huefner et al.
(13S,9Z,11E)-13-Hydroxy-9,11-tetradecadienoic acid (14, C14H24O3)
A 1 N solution of TBAF inTHF (1.3cm3, 1.3 mmol)was added toa solutionof150 mgof13 (0.423 mmol)
in 5 cm3 of abs. THF under Ar and it was stirred for 70min. After evaporation under reduced pressure the
residue was dissolved in 40 cm3 of CH2Cl2, washed with 2ꢃ10 cm3 of 2 N H2SO4 and 3ꢃ20 cm3 of H2O,
dried over Na2SO4, and evaporated under reduced pressure. PLC with cyclohexane:EtOAc:AcOH¼
25:25:2 yielded 80mg (79%) of 14 as a colourless wax. Rf ¼ 0.41 (cyclohexane:EtOAc:AcOH¼
25:25:2); 1H NMR (400MHz, DMSO-d6): ꢀ ¼ 1.10 (d, J ¼ 6.6 Hz, H-14), 1.25 (m, H-4, 5, 6), 1.31 (quint,
J ¼ 6.3 Hz, H-7), 1.44 (quint, J ¼ 6.6Hz, H-3), 1.79 (s, br, CH-OH), 2.07 (t, J ¼ 7.0 Hz, H-2), 2.11 (q,
J ¼ 7.3 Hz, H-8), 4.17 (quint, J ¼ 6.2 Hz, H-13), 5.34 (dt, J ¼ 10.8, 7.7Hz, H-9), 5.65 (dd, J ¼ 15.0,
5.9 Hz, H-12), 5.92 (t, J ¼ 11.0 Hz, H-10), 6.38 (dd, J ¼ 15.0, 11.0 Hz, H-11) ppm; 13C NMR (100 MHz,
DMSO-d6): ꢀ ¼ 24.0 (C-14), 25.3 (C-3), 27.3 (C-8), 28.8, 28.9, and 29.0 (C-4, 5, 6), 29.3 (C-7), 35.3 (C-
2), 66.5 (C-13), 123.2 (C-11), 128.5 (C-10), 131.3 (C-9), 139.3 (C-12), 175.6 (C-1) ppm; IR (neat):
ꢁꢀ¼ 3398 (m, br), 2924 (s), 2854 (s), 1711 (s), 1562 (vs), 1462 (m), 1446 (m), 1423 (m), 1369 (m), 1280
(m), 1134 (m), 985 (m), 945 (m) cmꢄ1; UV-Vis (MeOH, c ¼ 1.27ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 229.5
(15800), 271.5 (1220) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 240 (Mþ, 2.1), 222 ((Mþ-H2O),
21.9), 207 ((222-Me), 1.2), 194 ((222-C2H4), 3.7), 179 (8.3), 164 (11.2), 161 (12.0), 136 (20.8), 121
27
(19.2), 107 (23.6), 95 (97.2), 81 (83.7), 79 (99.5), 67 (100.0), 55 (94.6); ½ꢂꢅD ¼ þ8:8ꢁ cm2 gꢄ1 (c ¼ 0.13,
27
MeOH); ½ꢂꢅ546 ¼ þ6:4ꢁ cm2 gꢄ1 (c ¼ 0.13, MeOH).
(13S,9E,11E)-Methyl 13-tert-butyldimethylsilyloxy-9,11-tetradecadienoate (15, C21H40O3Si)
(11Z)-Isomer 12 (240mg, 0.65mmol) and 284 mg of diphenyl disulfide (1.30 mmol) were dissolved in
8 cm3 of abs. benzene. The solution was filled into four 5 mm NMR tubes and Ar was bubbled through
for 5 min. The tubes were closed and placed in an irradiation apparatus and irradiated for 16h at room
temp. with a high pressure mercury lamp with a 1% potassium chromate filter in a thickness of 1 cm.
The reaction mixture was evaporated under reduced pressure. CC over 50g of silica with
cyclohexane:EtOAc¼ 9:1 gave 184 mg (77%) of 15 as a colourless oil. Rf ¼ 0.42 (cyclohexane:
1
EtOAc¼ 9:1); H NMR (400MHz, benzene-d6): ꢀ ¼ 2ꢃ0.21 (s, Si(CH3)2), 1.12 (s, C(CH3)3), 1.25
(m, H-4, 5, 6), 1.35 (d, J ¼ 6.3 Hz, H-14), 1.38 (m, H-7), 1.65 (quint, J ¼ 7.2 Hz, H-3), 2.09 (q,
J ¼ 7.1 Hz, H-8), 2.22 (t, J ¼ 7.4 Hz, H-2), 4.41 (quint, J ¼ 6.1 Hz, H-13), 5.74 (dt, J ¼ 14.8, 6.7Hz,
H-9), 5.75 (dd, J ¼ 14.8, 5.9 Hz, H-12), 6.18 (dd, J ¼ 14.9, 10.3Hz, H-10), 6.38 (dd, J ¼ 15.2, 10.6Hz,
H-11) ppm; 13C NMR (100 MHz, benzene-d6): ꢀ ¼ ꢄ4:6 and ꢄ4.3 (Si(CH3)2), 18.4 (C(CH3)3), 24.9
(C-14), 25.2 (C-3), 26.1 (C(CH3)3), 29.3 and 2ꢃ29.4 (C-4, 5, 6), 29.6 (C-7), 33.0 (C-8), 34.1 (C-2),
50.9 (OCH3), 69.5 (C-13), 129.1 (C-11), 130.4 (C-10), 134.3 (C-9), 137.4 (C-12), 173.3 (C-1) ppm; IR
(neat): ꢁꢀ¼ 2951 (s), 2929 (s), 2857 (s), 1743 (s), 1660 (w), 1472 (m), 1436 (m), 1362 (m), 1287 (m),
1253 (m), 1196 (m), 1170 (m), 1143 (m), 1090 (m), 989 (m), 836 (s), 777 (m) cmꢄ1; UV-Vis (CH2Cl2,
c ¼ 0.95ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 235.5 (16430) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z
(%) ¼ 368 (Mþ, 7.0), 353 ((Mþ-Me), 1.0), 321 (0.5), 311 ((Mþ-C4H9), 12.0), 279 ((311-CH4O),
14.8), 237 ((Mþ-OTBDMS), 1.8), 211 (6.7), 187 (4.8), 159 (2.8), 145 (4.8), 131 (4.7), 117 (16.9),
25
115 (7.9), 107 (20.0), 93 (23.0), 75 ((Me2Si¼OH)þ, 100), 73 (54.2), 59 (20.0); ½ꢂꢅD ¼ 0ꢁ cm2 gꢄ1
25
(c ¼ 0.09, CH2Cl2); ½ꢂꢅ546 ¼ 0ꢁ cm2 gꢄ1 (c ¼ 0.09, CH2Cl2).
(13S,9E,11E)-13-tert-Butyldimethylsilyloxy-9,11-tetradecadienoic acid (16, C20H38O3Si)
As described for 12 hydrolysis of 110 mg of 15 (0.30 mmol) with 127mg of LiOHꢃH2O gave 47 mg
(46%) of 16 as a colourless oil. Rf ¼ 0.37 (cyclohexane:EtOAc:AcOH ¼ 50:10:2.4); 1H NMR (400 MHz,
CDCl3): ꢀ ¼ 2ꢃ0.03 (s, Si(CH3)2), 0.88 (s, C(CH3)3), 1.19 (d, J ¼ 6.2 Hz, H-14), 1.28 (m, H-4, 5, 6), 1.32
(m, H-7), 1.60 (quint, J ¼ 7.2 Hz, H-3), 2.03 (q, J ¼ 7.0 Hz, H-8), 2.32 (t, J ¼ 7.5 Hz, H-2), 4.29 (quint,

Isomers of the 13-Hydroxy-2,4,9-tetradecatrienoic Acid
455
J ¼ 6.1 Hz, H-13), 5.54 (dd, J ¼ 15.0, 5.9 Hz, H-12), 5.60 (dt, J ¼ 14.8, 6.5 Hz, H-9), 5.97 (dd, J ¼ 14.8,
10.6Hz, H-10), 6.06 (dd, J ¼ 14.8, 10.3Hz, H-11) ppm; 13C NMR (100MHz, CDCl3): ꢀ ¼ ꢄ4:8 and
ꢄ4.6 (Si(CH3)2), 18.3 (C(CH3)3), 24.5 (C-14), 24.6 (C-3), 25.9 (C(CH3)3), 2ꢃ29.0 and 29.1 (C-4, 5, 6),
29.2 (C-7), 32.6 (C-8), 34.1 (C-2), 69.1 (C-13), 128.5 (C-11), 129.8 (C-10), 134.2 (C-9), 135.5 (C-12),
180.2 (C-1) ppm; IR (neat): ꢁꢀ¼ 3020 (m), 2929 (s), 2857 (s), 2677 (m, br), 1711 (s), 1661 (w), 1471 (m),
1463 (m), 1441 (m), 1412 (m), 1362 (m), 1287 (m), 1255 (s), 1142 (m), 1089 (m), 1049 (m), 989 (m), 835
(s), 776 (m) cmꢄ1; UV-Vis (CH2Cl2, c ¼ 1.96 ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 238.5 (12200) nm
24
(molꢄ1 dm3 cmꢄ1); MS (70 eV): no significant spectrum gageable; ½ꢂꢅD ¼ þ7:5ꢁ cm2 gꢄ1 (c ¼ 0.11,
24
CH2Cl2); ½ꢂꢅ546 ¼ 0ꢁ cm2 gꢄ1 (c ¼ 0.11, CH2Cl2).
(13S,9E,11E)-13-Hydroxy-9,11-tetradecadienoic acid (17, C14H24O3)
As described for 13 desilylation of 35 mg of 16 (0.10 mmol) with 0.30 cm3 of a 1 N solution of TBAF
in THF (0.30 mmol) afforded 14mg (59%) of 17 as a colourless oil. Rf ¼ 0.39 (silica,
1
cyclohexane:EtOAc:AcOH¼ 25:25:2); H NMR (400MHz, MeOH-d4): ꢀ ¼ 1.22 (d, J ¼ 5.9 Hz, H-
14), 1.33 (m, H-4, 5, 6), 1.39 (quint, J ¼ 6.4 Hz, H-7), 1.59 (quint, J ¼ 6.4 Hz, H-3), 2.07 (q, J ¼ 7.0 Hz,
H-8), 2.26 (t, J ¼ 7.3 Hz, H-2), 4.23 (quint, J ¼ 6.2 Hz, H-13), 5.57 (dd, J ¼ 15.2, 6.8 Hz, H-12), 5.66
(dt, J ¼ 14.7, 6.5 Hz, H-9), 6.01 (dd, J ¼ 15.0, 10.6Hz, H-10), 6.14 (dd, J ¼ 15.2, 10.5Hz, H-11) ppm;
13C NMR (100MHz, MeOH-d4): ꢀ ¼ 23.9 (C-14), 26.4 (C-3), 30.4 and 2ꢃ30.5 (C-4, 5, 6), 30.7 (C-7),
33.9 (C-8), 35.4 (C-2), 69.4 (C-13), 131.1 (C-11), 131.5 (C-10), 135.9 (C-9), 136.3 (C-12), 178.2 (C-1)
ppm; IR (neat): ꢁꢀ¼ 3368 (m, br), 2971 (m), 2928 (s), 2856 (s), 1710 (s), 1456 (m), 1411 (m), 1370 (s),
1280 (m), 1136 (m), 1058 (m), 990 (s), 943 (m) cmꢄ1; UV-Vis (MeOH, c ¼ 1.41ꢆ 10ꢄ4 mol dmꢄ3):
ꢃ
max (") ¼ 230.5 (17000) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 240 (Mþ, 3.0), 239 ((Mþ-H),
1.6), 222 ((Mþ-H2O), 26.5), 207 ((222-Me), 2.0), 194 ((222-C2H4), 3.1), 179 (8.1), 164 (14.1), 161
(10.4), 136 (15.2), 121 (15.4), 104 (25.6), 95 (71.9), 81 (61.1), 79 (55.4), 67 (70.0), 55 (100);
20
20
½ꢂꢅD ¼ þ20ꢁ cm2 gꢄ1 (c ¼ 0.071, MeOH); ½ꢂꢅ546 ¼ þ7:0ꢁ cm2 gꢄ1 (c ¼ 0.071, MeOH).
(9S,5Z,7E)-9-tert-Butyldimethylsilyloxy-5,7-decadienol (19, C16H32O2Si)
and (9S,5E,7E)-9-tert-Butyldimethylsilyloxy-5,7-decadienol (20, C16H32O2Si)
To a suspension of 1.34 g of 18 (3.13 mmol) in 42cm3 of abs. THF at room temp. under Ar 3.9cm3 of a
1.6 N solution of BuLi in n-hexane (6.2mmol) were added and the mixture was stirred for 45min. A
solution of 675 mg of 10 (3.13 mmol) in 5 cm3 of abs. THF was added and stirring was continued for
60min. The mixture was evaporated under reduced pressure, diluted with 40cm3 of H2O, and was
extracted with 3ꢃ70cm3 of CH2Cl2. The combined organic phases were washed with 2ꢃ20cm3 of
brine, dried over Na2SO4, and evaporated under reduced pressure. CC over 400 g of silica with
cyclohexane:EtOAc¼ 1:1 gave 518 mg (58%) of a 2:3 mixture of 19 and 20. 19: Rf ¼ 0.51 (silica,
cyclohexane:EtOAc¼ 1:1); 1H NMR (400MHz, CDCl3): ꢀ ¼ 2ꢃ0.01 (s, Si(CH3)2), 0.85 (s, C(CH3)3),
1.18(d, J ¼ 6.6 Hz, H-10), 1.41 (quint, J ¼ 7.1Hz, H-3), 1.54 (quint, J ¼ 7.1Hz, H-2), 2.18 (q, J ¼ 7.3 Hz,
H-4), 3.62 (t, J ¼ 6.4 Hz, H-1), 4.33 (quint, J ¼ 6.0 Hz, H-9), 5.36 (dt, J ¼ 10.6, 7.7 Hz, H-5), 5.64 (dd,
J ¼ 15.0, 5.1 Hz, H-8), 5.95 (t, J ¼ 11.0 Hz, H-6), 6.41 (dd, J ¼ 15.0, 11.0Hz, H-7) ppm; 13C NMR
(100 MHz, CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.7 (Si(CH3)2), 18.3 (C(CH3)3), 24.4 (C-10), 25.8 (C-3), 25.9
(C(CH3)3), 27.4 (C-4), 32.3 (C-2), 62.7 (C-1), 68.9 (C-9), 123.3 (C-7), 128.4 (C-6), 131.2 (C-5), 137.9
(C-8) ppm; IR (neat): ꢁꢀ¼ 3347 (m), 2956 (s), 2930 (s), 2858 (s), 1472 (m), 1463 (m), 1255 (s), 1148 (m),
1074 (s), 984 (m), 835 (s), 776 (s) cmꢄ1; UV-Vis (CH2Cl2, c ¼ 0.67ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 236.5
(20400) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 284 (Mþ, 2.0), 269 ((Mþ-Me), 0.1), 253 ((Mþ-
OMe), 0.1), 227 ((Mþ-C4H9), 2.9), 211 (3.9), 183 (11.3), 171 (3.9), 155 (8.8), 145 (4.9), 135 (8.8), 119
(9.8), 117 (9.1), 115 (9.1) 107 (17.2), 105 (11.3), 93 (31.9), 91 (22.1), 79 (43.1), 77 (22.1), 75
19
((Me2Si¼OH)þ, 100), 73 (39.2), 67 (12.1), 57 (23.0), 55 (13.2); ½ꢂꢅD ¼ þ16ꢁ cm2 gꢄ1 (c ¼ 0.28,
19
CH2Cl2), ½ꢂꢅ546 ¼ þ18ꢁ cm2 gꢄ1 (c ¼ 0.28, CH2Cl2).

456
A. Huefner et al.
20: Rf ¼ 0.48 (silica, cyclohexane:EtOAc¼ 1:1); 1H NMR (400MHz, CDCl3): ꢀ ¼ 0.02 and 0.03 (s,
Si(CH3)2), 0.88 (s, C(CH3)3), 1.18 (d, J ¼ 6.6 Hz, H-10), 1.43 (m, H-3), 1.55 (m, H-2), 2.08 (q,
J ¼ 7.1 Hz, H-4), 3.61 (t, J ¼ 6.6 Hz, H-1), 4.29 (quint, J ¼ 6.2 Hz, H-9), 5.55 (dd, J ¼ 14.7, 5.5Hz,
H-8), 5.60 (dt, J ¼ 14.7, 7.0 Hz, H-5), 5.98 (dd, J ¼ 14.7, 10.6 Hz, H-6), 6.07 (ddd, J ¼ 14.7, 11.6,
1.1 Hz, H-7) ppm; 13C NMR (100MHz, CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.6 (Si(CH3)2), 18.3 (C(CH3)3), 25.8
and 25.9 (C-3, 10), 25.9 (C(CH3)3), 32.2 and 32.3 (C-2, 4), 62.8 (C-1), 69.0 (C-9), 128.3 (C-7), 130.1
(C-6), 133.7 (C-5), 135.9 (C-8) ppm; IR (neat): ꢁꢀ¼ 3347 (m), 2956 (s), 2930 (s), 2858 (s), 1472 (w),
1463 (w), 1255 (m), 1143 (w), 1073 (m), 988 (s), 835 (s), 776 (m) cmꢄ1; UV-Vis (CH2Cl2,
c ¼ 0.81ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 235.0 (16300) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z
(%) ¼ 284 (Mþ, 3.9), 269 ((Mþ-Me) 0.1), 253 ((Mþ-OMe), 0.1), 227 ((Mþ-C4H9), 2.0), 211 (4.9),
183 (8.8), 171 (3.9), 155 (7.8), 145 (6.7), 135 (13.2), 119 (6.7), 117 (12.7), 115 (11.8), 107 (19.1), 105
(10.8), 93 (41.2), 91 (20.1), 79 (42.8), 77 (19.2), 75 ((Me2Si¼OH)þ, 100), 73 (44.1), 67 (12.9), 57
19
19
(15.0), 55 (17.6); ½ꢂꢅD ¼ 0ꢁ cm2 gꢄ1 (c ¼ 0.31, CH2Cl2); ½ꢂꢅ546 ¼ 0ꢁ cm2 gꢄ1 (c ¼ 0.31, CH2Cl2).
(9S,5Z,7E)-9-tert-Butyldimethylsilyloxy-5,7-decadienal (21, C16H30O2Si)
and (9S,5E,7E)-9-tert-Butyldimethylsilyloxy-5,7-decadienal (22, C16H30O2Si)
To a solution of 729 mg of PCC (3.38 mmol) in 17cm3 of abs. CH2Cl2 four drops of pyridine were
added . After stirring for a few min at room temp. 469mg of the (Z=E) mixture 19 þ 20 (1.65 mmol) in
4.5 cm3 of abs. CH2Cl2 were added and stirred for further 60 min at room temp. The reaction mixture
was filtered over a column (3cm diameter, 3 cm alumina, 3 cm silica, 3 cm alumina) and eluted with
CH2Cl2. Eluate and washings were dried over Na2SO4. Evaporation under reduced pressure yielded
401 mg (86%) of a 2:3 mixture of 21 and 22 as a colourless oil. 21: Rf ¼ 0.61 (silica,
cyclohexane:EtOAc¼ 2:1); 1H NMR (400MHz, CDCl3): ꢀ ¼ 2ꢃ0.03 (s, Si(CH3)2), 0.86 (s,
C(CH3)3), 1.20 (d, J ¼ 6.2 Hz, H-10), 1.70 (quint, J ¼ 7.4Hz, H-3), 2.19 (q, J ¼ 7.6 Hz, H-4), 2.41
(td, J ¼ 7.7, 1.5 Hz, H-2), 4.33 (quint, J ¼ 5.9 Hz, H-9), 5.32 (dt, J ¼ 10.6, 7.7 Hz, H-5), 5.65 (dd,
J ¼ 15.0, 5.8Hz, H-8), 5.98 (t, J ¼ 11.5Hz, H-6), 6.38 (dd, J ¼ 15.0, 11.4Hz, H-7), 9.73 (t, J ¼ 1.5 Hz,
H-1) ppm; 13C NMR (100MHz, CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.7 (Si(CH3)2), 18.3 (C(CH3)3), 21.9 (C-3),
24.4 (C-10), 25.8 (C(CH3)3), 26.9 (C-4), 43.2 (C-2), 68.1 (C-9), 123.0 (C-7), 129.3 (C-6), 129.9 (C-5),
138.6 (C-8), 202.3 (C-1) ppm; IR (neat): ꢁꢀ¼ 2956 (s), 2929 (s), 2887 (m), 2857 (s), 1728 (s), 1472
(w), 1463 (w), 1256 (s), 996 (s), 952 (w), 835 (s), 776 (m) cmꢄ1; UV-Vis (CH2Cl2,
c ¼ 1.4 ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 238.5 (15900) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z
(%) ¼ 282 (Mþ, 0.1), 225 ((Mþ-C4H9), 15.2), 207 (1.0), 197 (1.0), 181 (7.8), 169 (6.7), 157 (3.9),
143 (6.4), 133 (13.7), 119 (13.7), 107 (11.8), 105 (19.0), 95 (16.8), 91 (23.0), 79 (31.9), 77 (13.7), 75
22
((CH3)2Si¼OH)þ, 100), 73 (38.7), 67 (9.1), 57 (11.0), 55 (8.2); ½ꢂꢅD ¼ 21ꢁ cm2 gꢄ1 (c ¼ 0.16,
22
CH2Cl2); ½ꢂꢅ546 ¼ 21ꢁ cm2 gꢄ1 (c ¼ 0.16, CH2Cl2).
22: Rf ¼ 0.61 (silica, cyclohexane:EtOAc¼ 2:1); 1H NMR (400MHz, CDCl3): ꢀ ¼ 2ꢃ0.03 (s,
Si(CH3)2), 0.88 (s, C(CH3)3), 1.18 (d, J ¼ 6.2 Hz, H-10), 1.71 (quint, J ¼ 7.3 Hz, H-3), 2.10 (q,
J ¼ 7.2 Hz, H-4), 2.42 (t, J ¼ 7.1Hz, H-2), 4.30 (quint, J ¼ 6.0 Hz, H-9), 5.55 (dt, J ¼ ca. 15, ca.
7 Hz, H-5), 5.57 (dd, J ¼ ca. 15, ca. 6 Hz, H-8), 5.98 (dd, J ¼ 14.7, 10.3Hz, H-6), 6.07 (dd,
J ¼ 14.7, 10.6Hz, H-7), 9.74 (s, H-1) ppm; 13C NMR (100 MHz, CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.6
(Si(CH3)2), 18.3 (C(CH3)3), 21.6 (C-3), 24.5 (C-10), 25.9 (C(CH3)3), 31.8 (C-4), 43.2 (C-2), 68.9
(C-9), 128.0 (C-7), 130.9 (C-6), 132.4 (C-5), 136.5 (C-8), 202.4 (C-1) ppm; IR (neat): ꢁꢀ¼ 3430 (w),
2956 (m), 2930 (s), 2858 (m), 1689 (m), 1472 (w), 1463 (w), 1255 (m), 1092 (w), 989 (w), 836 (s),
777 (m) cmꢄ1
;
UV-Vis (CH2Cl2, c ¼ 1.2 ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 236.0 (15700) nm
(molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 281 ((Mþ-1), 0.1), 267 ((Mþ-Me), 1.0), 225
((Mþ-C4H9), 7.8), 211 (2.0), 197 (2.0), 181 (8.8), 169 (6.8), 157 (5.9), 143 (6.8), 133 (16.1), 119
(14.2), 107 (18.1), 105 (27.8), 95 (20.0), 91 (31.3), 79 (47.9), 77 (20.0), 75 ((Me2 Si¼OH)þ, 100), 73
22
22
(43.9), 67 (10.9), 57 (20.0), 55 (9.8); ½ꢂꢅD ¼ 0ꢁ cm2 gꢄ1 (c ¼ 0.073, CH2Cl2), ½ꢂꢅ546 ¼ 0ꢁ cm2 gꢄ1
(c ¼ 0.073, CH2Cl2).

Isomers of the 13-Hydroxy-2,4,9-tetradecatrienoic Acid
457
(13S,2E,11E)-Ethyl 13-tert-butyldimethylsilyloxy-2,4,9,11-tetradecatetraenoate
(23, mixture of four 4,9-isomers, C22H38O3Si)
Under Ar 646 mg of 5 (1.42 mmol) and 851 mg of K2CO3 in 30cm3 of abs. DMF were heated to
120ꢁC. A solution of 401 mg of aldehydes 21þ 22 (1.42 mmol) in 7 cm3 of abs. DMF was added and
stirring at 120ꢁC was continued for 1.5 h. After cooling to room temp. the reaction mixture was poured
into 75 cm3 of H2O and extracted with 3ꢃ120 cm3 of Et2O. The combined extracts were washed with
185 cm3 of brine, dried over Na2SO4, and the solvent was evaporated under reduced pressure. CC over
100 g of silica with cyclohexane:EtOAc¼ 20:1 gave 257 mg (48%) of the (Z=E) mixture 23 as a
colourless oil. Rf: 0.28 (silica, cyclohexane:EtOAc¼ 20:1).
(13S,2E,4E,9E,11E)-Ethyl 13-tert-butyldimethylsilyloxy-2,4,9,11-tetradecatetraenoate
(24, C22H38O3Si)
The mixture 23 (254 mg, 0.67 mmol) and 586 mg of diphenyl disulfide (2.68 mmol) were dissolved in
10cm3 of abs. benzene. The solution was filled into three 5 mm NMR tubes and Ar was bubbled through
for 5 min. The tubes were closed and placed in an irradiation apparatus and irradiated for 90h at room
temp. with a high pressure mercury lamp with a 1% potassium chromate filter in a thickness of 1 cm. The
reaction mixture was evaporated under reduced pressure. CC over 50g of silica with cyclohexane:
EtOAc¼ 20:1 gave 133 mg (45%) of 24 as a colourless oil. Rf ¼ 0.24 (silica, cyclohexane:EtOAc¼ 20:1);
1H NMR (400 MHz, benzene-d6): ꢀ ¼ 0.20 (s, Si(CH3)2), 1.12 (s, C(CH3)3), 1.13 (t, J ¼ 7.0 Hz,
O–CH2CH3), 1.32 (quint, J ¼ 7.3 Hz, H-7), 1.34 (d, J ¼ 6.6 Hz, H-14), 1.89 (q, J ¼ 7.5 Hz, H-8), 1.97
(q, J ¼ 7.5 Hz, H-6), 4.18 (q, J ¼ 7.2 Hz, O–CH2CH3), 4.39 (quint, J ¼ 6.2Hz, H-13), 5.64 (dt, J ¼ 15.1,
7.2 Hz, H-9), 5.74 (dt, J ¼ 15.8, 6.7 Hz, H-5), 5.76 (dd, J ¼ 14.2, 6.0 Hz, H-12), 5.97 (dd, J ¼ 15.2,
10.9Hz, H-4), 6.00 (d, J ¼ 15.4Hz, H-2), 6.13 (dd, J ¼ 15.3, 10.6Hz, H-10), 6.38 (dd, J ¼ 14.8,
10.2Hz, H-11), 7.57 (dd, J ¼ 15.4, 11.2Hz, H-3) ppm; 13C NMR (100MHz, benzene-d6): ꢀ ¼ ꢄ4:6
and ꢄ4.3 (Si(CH3)2), 14.4 (O–CH2CH3), 18.4 (C(CH3)3), 24.9 (C-14), 26.1 (C(CH3)3), 28.4 (C-7), 32.3
(C-6), 32.4 (C-8), 60.1 (O–CH2CH3), 69.4 (C-13), 120.1 (C-2), 128.8 (C-11), 129.0 (C-4), 130.9 (C-10),
1
133.4 (C-9), 136.5 (C-12), 143.7 (C-5), 145.0 (C-3), 166.8 (C-1) ppm; H NMR (400MHz, CDCl3):
ꢀ ¼ 2ꢃ0.02 (s, Si(CH3)2), 0.86 (t, J ¼ 6.2 Hz, O–CH2CH3), 0.87 (s, C(CH3)3), 1.18 (d, J ¼ 6.6 Hz, H-14),
1.50 (quint, J ¼ 7.3 Hz, H-7), 2.06 (q, J ¼ 7.0 Hz, H-8), 2.14 (q, J ¼ 7.1Hz, H-6), 4.17 (q, J ¼ 7.1 Hz,
O–CH2CH3), 4.29 (quint, J ¼ 6.1Hz, H-13), 5.54 (m, H-12), 5.58 (m, H-9), 5.75 (d, J ¼ 15.4 Hz, H-2),
5.98 (m, H-10), 6.05 (m, H-11), 6.13 (m, H-4), 6.13 (m, H-5), 7.23 (dd, J ¼ 15.4, 9.9 Hz, H-3) ppm;
13C NMR (100MHz, CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.6 (Si(CH3)2), 14.3 (O–CH2CH3), 18.2 (C(CH3)3), 24.5
(C-14), 25.9 (C(CH3)3), 28.2 (C-7), 32.0 (C-8), 32.3 (C-6), 60.1 (O–CH2CH3), 68.9 (C-13), 119.3 (C-2),
128.2 (C-11), 128.6 (C-4), 130.4 (C-10), 133.1 (C-9), 136.1 (C-12), 144.0 (C-5), 144.9 (C-3), 167.2 (C-1)
ppm; IR (neat): ꢁꢀ¼ 3436 (w), 2956 (s), 2930 (s), 2858 (m), 1716 (s), 1645 (m), 1472 (w), 1463 (w),
1368 (m), 1256 (s), 1141 (m), 1093 (w), 1000 (m), 836 (s), 777 (m) cmꢄ1; UV-Vis (CH2Cl2, c ¼
1.5 ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 255.5 (14300) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 378
(Mþ, 0.1), 363 ((Mþ-Me), 1.0), 321 ((Mþ-C4H9), 38.2), 305 ((Mþ-C3H5O2), 1.0), 295 (18.3), 275
(2.9), 249 (2.9), 223 (2.9), 207 (1.0), 185 (2.5), 173 (9.8), 147 (14.7), 131 (16.7), 119 (14.7), 117
(18.1), 105 (15.7), 103 (14.2), 91 (25.5), 79 (24.0), 75 ((Me2Si¼OH)þ, 100), 73 (33.3), 67 (11.8), 57
22
22
(19.6); ½ꢂꢅD ¼ þ5:3ꢁ cm2 gꢄ1 (c ¼ 0.13, CH2Cl2); ½ꢂꢅ546 ¼ þ3:1ꢁ cm2 gꢄ1 (c ¼ 0.13, CH2Cl2).
(13S,2E,4E,9E,11E)-13-tert-Butyldimethylsilyloxy-2,4,9,11-tetradecatetraenoic acid
(25, C20H34O3Si)
A solution of 81 mg of LiOHꢃ H2O (1.9mmol) in 1.0cm3 of H2O was added to 73mg of 24
(0.19 mmol) in 1.9 cm3 of abs. THF under Ar. After stirring under reflux for 18h and cooling to room
temp. the reaction mixture was poured into 6.4 cm3 of 2 N H2SO4 and extracted with 3ꢃ10 cm3 of
Et2O. The combined organic layers were washed with 2ꢃ3 cm3 of 2 N H2SO4 and 2ꢃ3 cm3 of brine,

458
A. Huefner et al.
dried over Na2SO4, and the solvent was evaporated under reduced pressure. CC over ca. 2 g of silica
with cyclohexane:EtOAc:AcOH¼ 35:15:2 gave 63 mg (94%) of 25 as a colourless oil. Rf ¼ 0.31 (silica,
cyclohexane:EtOAc:AcOH¼ 35:15:2); 1H NMR (400MHz, CDCl3): ꢀ ¼ 2ꢃ0.04 (s, Si(CH3)2), 0.89 (s,
C(CH3)3), 1.19 (d, J ¼ 6.6Hz, H-14), 1.52 (quint, J ¼ 7.3 Hz, H-7), 2.08 (q, J ¼ 7.1 Hz, H-8), 2.18 (q,
J ¼ 6.8 Hz, H-6), 4.30 (quint, J ¼ 6.2 Hz, H-13), 5.56 (dd, J ¼ 15.8, 4.8Hz, H-12), 5.58 (dt, J ¼ 15.0,
7.0 Hz, H-9), 5.76 (d, J ¼ 15.4 Hz, H-2), 5.99 (m, H-10), 6.04 (m, H-11), 6.17 (m, H-4), 6.17 (m, H-5),
7.32 (dd, J ¼ 15.4, 9.9 Hz, H-3) ppm; 13C NMR (100MHz, CDCl3): ꢀ ¼ ꢄ4:8 and ꢄ4.6 (Si(CH3)2),
18.3 (C(CH3)3), 24.5 (C-14), 25.9 (C(CH3)3), 28.2 (C-7), 32.0 (C-8), 32.4 (C-6), 67.0 (C-13), 118.4 (C-
2), 128.2 (C-11), 128.5 (C-4), 130.5 (C-10), 133.1 (C-9), 136.1 (C-12), 145.6 (C-5), 147.3 (C-3), 172.6
(C-1) ppm; IR (neat): ꢁꢀ¼ 2956 (s), 2929 (s), 2857 (m), 2667 (w, vbr), 1690 (s), 1640 (m), 1472 (w),
1463 (w), 1417 (m), 1305 (m), 1275 (m), 1257 (s), 1143 (m), 1089 (w), 1000 (m), 990 (m), 835 (s), 776
(m) cmꢄ1; UV-Vis (CH2Cl2, c ¼ 0.58ꢆ 10ꢄ4 mol dmꢄ3): ꢃmax (") ¼ 236.0 (23100), 263.0 (26400) nm
(molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 350 (Mþ, 1.1), 293 ((Mþ-C4H9), 4.1), 275 ((293-H2O),
9.0), 249 (7.7), 235 (3.6), 218 (8.9), 211 (13.1), 185 (25.5), 173 (24.3), 159 (13.7), 147 (15.4), 133
(27.5), 117 (24.4), 107 (22.9), 91 (24.4), 81 (26.1), 79 (36.5), 75 ((Me2Si¼OH)þ, 100), 73 (62.7), 55
21
21
(20.0); ½ꢂꢅD ¼ þ5:0ꢁ cm2 gꢄ1 (c ¼ 0.30, CH2Cl2); ½ꢂꢅ546 ¼ þ4:3ꢁ cm2 gꢄ1 (c ¼ 0.30, CH2Cl2).
(13S,2E,4E,9E,11E)-13-Hydroxy-2,4,9,11-tetradecatetraenoic acid (26, C14H20O3)
In a procedure as described for 13 desilylation of 25mg of 25 (0.071mmol) with 0.21cm3 of a 1 N
solution of TBAF in THF (1.3mmol) afforded 9 mg (54%) of 26 as a colourless oil. Rf ¼ 0.36 (silica,
cyclohexane:EtOAc:AcOH¼ 25:25:2); 1H NMR (400 MHz, MeOH-d4): ꢀ ¼ 1.22 (d, J ¼ 6.5 Hz, H-14),
1.54 (quint, J ¼ 7.3 Hz, H-7), 2.11 (q, J ¼ 7.0Hz, H-8), 2.19 (q, J ¼ 7.0 Hz, H-6), 4.24 (quint,
J ¼ 6.2 Hz, H-13), 5.60 (dd, J ¼ 15.2, 6.4Hz, H-12), 5.67 (dt, J ¼ 14.7, 7.0 Hz, H-9), 5.78 (d,
J ¼ 15.8, Hz, H-2), 6.04 (dd, J ¼ 15.2, 10.5Hz, H-10), 6.16 (m, H-5, 11), 6.23 (dd, J ¼ 15.2,
10.5Hz, H-4), 7.23 (dd, J ¼ 15.2, 10.0 Hz, H-3) ppm; 13C NMR (100MHz, MeOH-d4): ꢀ ¼ 23.9
(C-14), 29.8 (C-7), 33.4 (C-8), 33.7 (C-6), 69.3 (C-13), 121.0 (C-2), 130.3 (C-4), 130.9 (C-11),
132.0 (C-10), 135.2 (C-9), 136.6 (C-12), 145.6 (C-5), 147.0 (C-3), 171.2 (C-1) ppm; IR (neat):
ꢁꢀ¼ 3420 (m, br), 2934 (s), 2868 (s), 1715 (s), 1644 (m), 1455 (m), 1436 (m), 1374 (m), 1258 (s),
1182 (m), 1141 (m), 1061 (m), 1002 (m), 978 (m) cmꢄ1; UV-Vis (MeOH, c ¼ 0.54 10ꢄ4 mol dmꢄ3):
ꢃmax (") ¼ 232.0 (29900), 254.0 (28800) nm (molꢄ1 dm3 cmꢄ1); MS (70 eV): m=z (%) ¼ 218 ((Mþ-
H2O), 3.3), 199 ((218-Me), 8.5), 183 (6.9), 173 (7.4), 147 (12.0), 131 (17.0), 107 (41.9), 95 (40.1), 81
21
21
(52.3), 79 (93.9), 67 (53.0), 55 (100); ½ꢂꢅD ¼ þ15ꢁ cm2 gꢄ1 (c ¼ 0.065, MeOH); ½ꢂꢅ546 ¼ 0ꢁ cm2 gꢄ1
(c ¼ 0.065, MeOH).
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¨
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