A.M. Twidle et al. / Phytochemistry 141 (2017) 61e69
67
(8H, m, H-2, H-3, H-14, H-15), 1.69e1.77 (8H, m, H-4, H-6, H-11, H-
13), 2.14e2.18 (4H, m, H-7, H-10), 3.01 (6H, s, 2 x OSO2CH3),
4.70e4.73 (2H, m, H-5, H-12), 5.38e5.40 (2H, m, H-8, H-9); dC
(100 MHz; CDCl3) 13.9 (C-1, C-16), 22.4 (C-2, C-15), 22.9 (C-7, C-10),
27.0 (C-3, C-14), 34.2 (C-4, C-6, C-11, C-13), 38.7 (OSO2CH3), 83.6 (C-
5, C-12). 129.3 (C-8, C-9); IR: nmax(film)/cmꢁ1; 2959, 2934, 2874,
1460, 1349, 1331, 1169, 971, 903 and 732; HRMS (ESIþ) found
(MNaþ): 435.1842 C18H36NaO6S2 requires 435.1846.
mixture was warmed to r.t., and stirred for 2 h. The mixture was
then cooled again to 0 ꢂC and the excess LiAlH4 was quenched with
successive additions of water (1 mL), aq. 10% NaOH (1 mL) and
water (3 mL). The mixture was extracted with DCM (20 mL ꢀ 2).
The combined organic extracts were washed with brine (20 mL)
and dried (MgSO4). The solvent was removed under vacuum to give
(9Z)-octadecen-1-ol (7) (2.45 g, 9.14 mmol, 91% yield) as a clear
colourless oil. dH (400 MHz; CDCl3; Me4Si) 0.88 (3H, t, J ¼ 8.0 Hz, H-
18),1.27e1.37 (24H, m, H-3, H-4, H-5, H-6, H-7, H-12, H-13, H-14, H-
15, H-16, H-17), 1.53e1.60 (3H, m, H-2, OH), 1.99e2.04 (4H, m, H-8,
H-11), 3.64 (2H, t, J ¼ 8.0 Hz, H-1), 5.31e5.39 (2H, m, H-9, H-10). The
1H NMR data matched that reported in literature (Sakai et al., 2011).
4.6.5. Synthesis of (8Z)-hexadecene (5)
To a cooled (0 ꢂC) suspension of LiAlH4 (155 mg, 4.08 mmol) in
dry THF (5 mL), a solution of dimesylate (4) (280 mg, 0.68 mmol) in
dry THF (5 mL) was added dropwise, under an argon atmosphere.
The reaction mixture was then slowly brought to reflux and reacted
for 1 h. The reaction was quenched with the sequential addition of
water (1 mL), aq. 10% NaOH (1 mL) and water (3 mL). The resulting
mixture was filtered and rinsed with pentane (20 mL ꢀ 2). The
organic layers were combined, washed with brine (20 mL) then
dried (MgSO4). The solvent was removed under vacuum and the
crude product was purified by column chromatography (silica gel,
pentane) to give (8Z)-hexadecene (5) (80 mg, 0.36 mmol, 53% yield,
97% chemical purity and 97% isomeric purity by GC) as a clear
colourless oil. dH (400 MHz; CDCl3; Me4Si) 0.87e0.90 (6H, m, H-1,
H-16), 1.24e1.35 (20H, m, H-2, H-3, H-4, H-5, H-6, H-11, H-12, H-13,
H-14, H-15), 1.99e2.04 (4H, m, H-7, H-10), 5.31e5.39 (2H, m, H-8,
H-9). The 1H NMR data matched that reported in literature
4.8.2. Synthesis of olealdehyde (8)
To a solution of alcohol (7) (2.40 g, 8.96 mmol) in DCM (30 mL),
Dess-Martin periodinane (4.24 g, 10 mmol) was added. The reaction
mixture was stirred for 3 h then quenched with aq. sat. NaHCO3
(20 mL). The aqueous phase was extracted with DCM (20 mL ꢀ 2)
and the combined organic layers were dried (MgSO4). The solvent
was removed under vacuum to give the crude product which was
purified by column chromatography (silica gel, pentane: DCM
gradient) to give olealdehyde (8) (1.36 g, 5.11 mmol, 57% yield) as a
clear colourless oil. dH (400 MHz; CDCl3; Me4Si) 0.88 (3H, t,
J ¼ 8.0 Hz, H-18), 1.27e1.31 (20H, m, H-4, H-5, H-6, H-7, H-12, H-13,
H-14, H-15, H-16, H-17), 1.61e1.65 (2H, m, H-3), 1.99e2.03 (4H, m,
H-8, H-11), 2.40e2.44 (2H, m, H-2), 5.32e5.39 (2H, m, H-9, H-10),
9.76 (1H, t, J ¼ 2.0 Hz, H-1). The 1H NMR data matched that reported
in literature (Uyanik et al., 2009).
€
(Soderman and Schwan, 2012).
4.7. Synthesis of (3Z,6Z,9Z)-heptadecatriene
4.8.3. Synthesis of (10Z)-nonadecen-2-ol (9)
To a solution of linolenic acid (278 mg, 1.00 mmol) and DMF
To a solution of aldehyde (8) (540 mg, 2.03 mmol) in dry THF
(5 mL) at 0 ꢂC, 3 M methyl magnesium bromide (2.0 mL, 6 mmol) in
Et2O was added dropwise under argon. The reaction mixture was
allowed to warm to r.t. over 1 h, then heated at reflux for 2 h. The
mixture was then cooled to 0 ꢂC and quenched with water (20 mL).
The mixture was extracted with Et2O (20 mL ꢀ 3) and the combined
organic layers were dried (MgSO4). The solvent was removed under
vacuum and the crude product was purified by column chroma-
tography (silica gel, hexane: EtOAc gradient) to give (10Z)-non-
adecen-2-ol (9) (435 mg, 1.54 mmol, 76% yield) as a clear colourless
oil. dH (400 MHz; CDCl3; Me4Si) 0.86e0.90 (3H, m, H-19), 1.18e1.21
(3H, m, H-1), 1.21e1.60 (25H, m, H-3, H-4, H-5, H-6, H-7, H-8, H-13,
H-14, H-15, H-16, H-17, H-18, OH), 1.99e2.04 (4H, m, H-9, H-12),
3.79 (1H, br s, H-2), 5.31e5.36 (2H, m, H-10, H-11); dC (100 MHz;
CDCl3) 14.1 (C-19), 22.7 (C-18), 23.5 (C-1), 25.8 (C-4), 27.19 and
27.21 (C-9, C-12), 29.2, 29.3, 29.5, 29.6, 29.7, 29.8 (C-5, C-6, C-7, C-8,
C-13, C-14, C-15, C-16), 31.9 (C-17), 39.4 (C-3), 68.2 (C-2), 129.8 and
130.0 (C-10, C-11); IR: nmax(film)/cmꢁ1; 3351, 2959, 2923, 2854,
1465, 1376, and 722; HRMS (ESIþ) found (MNaþ): 305.2807
(50
mL, 0.65 mmol) in dry CHCl3 (5 mL), under an argon atmosphere,
a solution of oxalyl chloride (94
mL, 1.09 mmol) in dry CHCl3 (1 mL)
was added dropwise. After 1 h the mixture was heated at reflux for
a further 3 h. The resulting acid chloride was cooled to r.t. and put
aside for use in the next part of the reaction.
2-Mercaptopyridine, N-oxide sodium salt (179 mg, 1.20 mmol)
and DMAP (1 mg, 0.008 mmol) were dissolved in dry CHCl3 (5 mL),
then heated to reflux under an argon atmosphere to form a white
suspension. The acid chloride prepared above was added dropwise
with concomitant irradiation from a tungsten lamp (240 V, 500 W)
producing a bright yellow solution. After 90 min at reflux the re-
action mixture had faded to a dull yellow/brown colour and was
allowed to cool to r.t. Once cooled, the mixture was diluted with
DCM (20 mL) and washed with 1 M HCl and brine (20 mL) and dried
(MgSO4). The solvent was then removed under vacuum and the
crude product was purified by column chromatography (silica gel,
pentane) to give (3Z,6Z,9Z)-heptadecatriene (6) (140 mg,
0.60 mmol, 60% yield, 97% chemical purity and 85% isomeric purity
by GC) as a clear yellow oil. Due to the low isomeric purity the
triene was subjected to further chromatography using AgNO3 (10%)
on silica gel (hexane: EtOAc gradient). The isomeric purity was
improved to 99%, determined by GC. dH (400 MHz; CDCl3; Me4Si)
0.88 (3H, t, J ¼ 4.0 Hz, H-1), 0.98 (3H, t, J ¼ 4.0 Hz, H-17), 1.27e1.37
(10H, m, H-12, H-13, H-14, H-15, H-16), 2.03e2.10 (4H, m, H-2, H-
11), 2.75e2.83 (4H, m, H-5, H-8), 5.30e5.43 (6H, m, H-3, H-4, H-6,
H-7, H-9, H-10). The 1H NMR data matched that reported in liter-
ature (Silk et al., 2015).
C19H38NaO requires 305.2815.
4.8.4. Synthesis of (10Z)-nonadecen-2-yl methanesulfonate (10)
To a stirred solution of alcohol (9) (400 mg, 1.42 mmol) and Et3N
(396
chloride (219
m
L, 2.84 mmol) in dry DCM (10 mL) under argon at 0 ꢂC, mesyl
mL, 2.84 mmol) was added dropwise. The mixture was
allowed to warm to r.t. and stirred for 2 h. The mixture was washed
with water (10 mL), 1M HCl (5 mL ꢀ 2), aq. sat. NaHCO3 solution
(20 mL) and brine (20 mL) and dried (MgSO4). The solvent was
removed under vacuum to give (10Z)-nonadecen-2-yl meth-
anesulfonate (10) (482 mg, 1.34 mmol, 94% yield) as a pale yellow-
grey oil which was used in the next step without further purifica-
tion. dH (400 MHz; CDCl3; Me4Si) 0.86e0.90 (3H, m, H-19),
1.27e1.41 (24H, m, H-3, H-4, H-5, H-6, H-7, H-8, H-13, H-14, H-15,
H-16, H-17, H-18, OH),1.41 (3H, d, J ¼ 4.0 Hz, H-1),1.99e2.04 (4H, m,
H-9, H-12), 2.99 (3H, s, OSO2CH3), 4.75e4.83 (1H, m, H-2),
4.8. Synthesis of (9Z)-nonadecene
4.8.1. Synthesis of (9Z)-octadecen-1-ol (7)
To a cool (0 ꢂC) suspension of LiAlH4 (1.14 g, 30.0 mmol) in dry
THF (20 mL), a solution of oleic acid (2.82 g, 10 mmol) in dry THF
(10 mL) was added dropwise with constant stirring. The reaction