Electronic supplementary material
Synthesis of deuterated compounds
Methyl (9Z,12Z,15Z)-2,2-dideuterooctadeca-9,12,15-trienoate (2)
Sodium metal (1.2 g, 52.2 mmol) was dissolved in CH3OD (50 ml). Methyl linolenate (1.0 g,
3.42 mmol, 1) was added and the resulting reaction mixture was heated to reflux for 6h. The
mixture was diluted with diethyl ether and 2M aqueous HCl was added [S1]. The organic
phase was separated and the aqueous phase was extracted twice with diethyl ether. The
combined organic phases were dried with magnesium sulfate, and the solvents were removed
under reduced pressure. The product mixture of the α-deuterated ester 2 and the
corresponding free acid was purified by column chromatography on silica gel with
pentane/diethyl ether 5:1.
Yield: 0.71 g (71%). Rf = 0.89 (pentane/diethyl ether 5:1). 1H-NMR (200 MHz, CDCl3): 0.97
(t, J = 7.4 Hz, 3H, CH3), 1.29-1.32 (m, 4H, 2xCH2), 1.33-1.35 (m, 4H, 2xCH2), 1.57 (t, J = 7.7
Hz, 2H, CH2CD2CO), 2.03-2.08 (m, 4H, 2xCH2), 2.79-2.82 (m, 2H, 2xCH2), 3.63 (s,3H,
CH3), 5.28-5.43 (m, 6H, 6xCH). EI-MS (70 eV) m/z (%): = 294 (11) [M]+, 263 (6), 238 (7),
163 (4), 149 (13), 135 (15), 121 (20), 108 (41), 95 (51), 79 (100), 67 (59), 55 (28), 41 (35).
(9Z,12Z,15Z)-1,1,2,2-Tetradeuterooctadeca-9,12,15-trien-1-ol (3)
A suspension of lithium aluminium deuteride (1.88 g, 44.8 mmol) in anhydrous diethyl ether
was cooled to 0°C under a nitrogen atmosphere. The deuterated ester 2 (3.23 g, 11.2 mmol)
was added in 60 ml of anhydrous diethyl ether. The suspension was allowed to warm up to
room temperature and the progress of the reaction was controlled by TLC. After the
consumption of the ester was complete, a 2M aqueous HCl-solution was added until two clear
phases were formed and the organic phase was separated. The aqueous layer was extracted
twice with diethyl ether and the organic phases were combined. The combined organic
phases were dried with MgSO4 and the solvents were removed under reduced pressure. The
crude product was purified by column chromatography on silica gel with pentane/diethyl
ether 1:1. [S2]
Yield: 2.98 g (95%). Rf = 0.45 (pentane/diethyl ether 1:1). 1H-NMR (400 MHz, CDCl3) : 0.98
(t, J = 7.6 Hz, 3H, CH3), 1.29-1.32 (m, 4H, 2x CH2), 1.33-1.35 (m, 6H, 3x CH2), 2.03–
2.08 (m,4H, 2x CH2), 2.79-2.82 (m, 4H, 2x CH2), 5.28-5.43 (m, 6H, 6xCH). 13C-NMR
(100 MHz, CDCl3): 14.3 (CH3), 20.5 (CH2), 25.5 (CH2), 25.6 (CH2), 26.2 (CH2 CD2), 27.2
(CH2), 29.2 (CH2), 29.3 (CH2), 29.5 (CH2), 29.6 (CH2), 127.1 (CH), 127.7 (CH),
128.3 (2xCH), 130.3 (CH), 131.9 (CH). EI-MS (70 eV) m/z (%): = 268 (8) [M]+, 212 (11),
149 (5), 135 (11), 121 (14), 108 (45), 95 (31), 93 (49), 79 (100), 67 (52), 55 (23), 41 (29).
(9Z,12Z,15Z)-1,1,2,2-Tetradeutero-1-iodoctadeca-9,12,15-triene (4)
An equimolar suspension of triphenyl phosphine (5.8 g, 22.2 mmol) and imidazole (1.51g,
22.2 mmol) in a solvent mixture containing anhydrous acetonitrile and anhydrous diethyl
ether in a ratio of 3:1 was prepared and cooled to 0°C under a nitrogen atmosphere, to which
iodine crystals (5.7g, 22.2 mmol) were added in portions. The mixture was stirred for 30
minutes at room temperature, followed by re-cooling to 0°C. The alcohol 3 (2.98g, 11.1
mmol) in anhydrous diethyl ether was added. [S3] The resulting reaction mixture was allowed
to warm up to room temperature and stirring was continued overnight. After completion of the
reaction aqueous saturated sodium hydrogen carbonate was added and the organic phase was
separated. The aqueous phase was washed twice with diethyl ether. The organic phases were
combined, dried with magnesium sulfate, and the solvents were removed under reduced
pressure. The crude product was purified by column chromatography on silica gel with
pentane/diethyl ether 5:1.
Yield: 3.5 g (84%). Rf = 0.93 (pentane/diethyl ether 5:1). 1H-NMR (400 MHz, CDCl3) : 0.98
(t, J = 7.5 Hz, 3H, CH3), 1.29-1.32 (m, 4H, 2x CH2), 1.33-1.35 (m, 6H, 3xCH2), 2.03-2.08
(m, 4H, 2x CH2), 2.81 (t, J = 5.7 Hz, 4H, 2x CH2), 5.28-5.43 (m, 6H, 6xCH). (100 MHz,
CDCl3): 14.3 (CH3), 20.6 (CH2), 25.5 (CH2), 25.6 (CH2), 27.2 (CH2), 28.5 (CH2), 29.2 (CH2),
29.3 (CH2), 29.6 (CH2), 30.3 (CH2), 127.1 (CH), 127.7 (CH), 128.3 (2xCH), 130.3 (CH),
132.0 (CH). EI-MS (70 eV) m/z (%): = 378 (11) [M]+, 322 (18), 159 (4), 149 (3), 135 (7), 121
(11), 108 (67), 93 (40), 79 (100), 67 (58), 55 (28), 41 (33).
(10Z,13Z,16Z)-2,2,3,3-Tetradeuterononadeca-10,13,16-triene-1-carbonitrile (5)
Anhydrous acetonitrile (0.475 g, 11.5 mmol) dissolved in dry THF (12 ml) at -78°C was
treated with n-BuLi (5 ml, 1.6M solution in hexane) under a nitrogen atmosphere. The
resulting reaction mixture was stirred at this temperature for 2 h, followed by the addition of
tetradeuterated iodide 141 (1.75 g, 4.62 mmol) dissolved in anhydrous THF (15 ml).[S4]
Stirring was continued at this temperature for 3 h, after which the mixture was warmed to
room temperature and stirred overnight. The mixture was hydrolyzed with water and extracted
with diethyl ether. The organic phase was separated and the aqueous phase was washed twice
with diethyl ether. The combined organic phase was dried over magnesium sulfate, and the
solvents were removed under reduced pressure. The crude product was purified by column
chromatography on silica gel using 10:1 pentane/diethyl ether as eluent mixture
Yield: 0.41 g (30%) .Rf = 0.27 (pentane/diethyl ether 10:1). 1H-NMR (400 MHz, CDCl3):
0.98 (t, J = 7.5 Hz, 3H, CH3), 1.29-1.32 (m, 4H, 2x CH2), 1.33-1.35 (m, 6H, 3x CH2), 2.032.08 (m, 4H, 2x CH2), 2.38 (s, 2H, CH2CN), 2.81 (t, J = 5.7 Hz, 4H, 2x CH2), 5.27-5.42 (m,
6H, 6xCH). 13C-NMR (100 MHz, CDCl3): 14.3 (CH3), 17.7 (CH2CN), 20.6 (CH2), 25.5
(CH2), 25.6 (CH2), 27.2 (CH2), 28.5 (CH2), 28.7 (CH2), 29.2 (CH2), 29.3 (CH2), 29.6 (CH2),
119.8 (CN), 127.1 (CH), 127.7 (CH), 128.2 (CH), 128.3 (CH), 130.3 (CH), 131.9 (CH). EIMS (70eV): m/z (%) = 291 (2) [M]+, 262 (2), 248 (2), 235 (2), 222 (6), 180 (2), 166 (3), 149
(5), 135 (9), 121 (12), 108 (24), 95 (53), 79 (100), 67 (73), 55 (41), 41 (61).
(11Z,14Z,17Z)-2,2,3,3,4,4-hexadeuteroicosa-11,14,17-trienoic acid (6)
To a solution of nitrile 5 (0.41 g, 1.40 mmol) in 60 % deuteroethanol in D2O, sodium deutero
hydroxide (1.1 g, 28 mmol) was added and the resulting reaction mixture was heated to reflux
for 24 h. After completion, the reaction mixture was treated with water and concentrated HCl.
[S5] The aqueous phase was extracted three times with diethyl ether. The separated organic
phases were combined, washed with water and saturated sodium chloride, dried with
magnesium sulfate, and filtered. After removal of solvent under vacuum, the crude product
was purified by column chromatography on silica gel with pentane/diethyl ether 2:1.
Yield: 0.195 g (45%). 1H-NMR (400 MHz, CDCl3): 0.97 (t, J = 7.6 Hz, 3H) 1.16 (t, J = 7.0
Hz, 2H, CH2CD2) 1.26-1.41 (m, 8H, 4xCH) 2.01-2.18 (m, 4H, 2x CH2) 2.81 (t, J = 5.6, 4H,
2x CH2) 5.27-5.42 (m, 6H, 6xCH). EI-MS (70eV) (MSTFA derivative): m/z (%) = 384 (16)
[M]+, 369 (75), 355 (6), 341 (5), 328 (7), 311 (4), 249 (2), 191 (6), 177 (7), 163 (8), 149 (18),
132 (40), 121 (27), 108 (54), 95 (61), 76 (100), 67 (50), 55 (20), 41 (23).
Literature
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[S2] Z. Yang, P. O. M. Hon, K. Y. Chui, Z. L. Xu, H. M. Chang, Tetrahedron Lett. 1991, 32,
2061-2064.
[S3] S. Hoarau, J. L. Fauchere, L. Pappalardo, M. L. Roumestant, P. Viallefont, Tetrahedron
Asymm. 1996, 7, 2585-2594.
[S4] M. G. Klein, J. H. Tumlinson, T. L. J. Ladd, R. E. Doolittle, J. Chem. Ecol. 1981, 7, 1-8.
[S5] C. V. Magatti, J. J. Kaminski, I. Rothberg, J. Org. Chem. 1991, 56, 3102-3108.