S. Zha, et al.
Fitoterapia145(2020)104639
(300 MHz) δ 0.89 (3H, deformed t, J = 7.0 Hz), 1.20–1.55 (19H, m),
1.55–1.68 (4H, m), 2.02 (2H, q, J = 7.0 Hz), 2.30 (2H, t, J = 7.6 Hz),
3.67 (3H, s), 4.02 (1H, q, J = 6.5 Hz), 5.44 (1H, dd, J = 15.4, 7.0 Hz),
5.63 (1H, dt, J = 15.4, 6.8 Hz). 13C NMR (75 MHz) δ 14.02, 22.47,
24.91, 25.44, 28.83, 29.09, 29.18, 29.32, 29.47 (×2), 31.32, 32.11,
34.07, 37.27, 51.42, 73.18, 132.17, 132.97, 174.33. DART-MS m/z (rel
intensity) 312 (15), 296 (22), 295 (100), 293 (38), 282 (21). HR-DART-
MS m/z [M + H-H2O]+ 295.26347 (calcd for C19H35O2: 295.26371).
(2H, m), 2.04 (3H, s), 3.64 (2H, t, J = 6.7 Hz), 5.17 (1H, q, J = 7.0 Hz),
5.36 (1H, m), 5.68 (1H, dt, J = 15.5, 6.8 Hz). 13C NMR (75 MHz) δ
14.07, 21.38, 22.62, 25.15, 25.60, 28.78, 28.95, 29.14, 29.18, 29.32,
29.44, 31.81, 32.11, 32.66, 34.46, 62.93, 75.12, 128.33, 134.31,
170.50. DART-MS m/z (rel intensity) 326 (22), 267 (100), 429 (61),
177 (56). HR-DART-MS [M + H-AcOH]+ m/z 267.26766 (calcd for
C
18H35O: 267.26879).
2.8.14. (E)-10-(Acetoxy)octadec-8-enoic acid (19)
2.8.10. (E)-11-hydroxyoctadec-12-enoic acid (3)
A mixture of 18 (66.5 mg, 0.204 mmol) and PDC (268 mg,
0.713 mmol) dry DMF (2 mL) was stirred at rt. for 17 h. The mixture
was poured into water, extracted twice with ether, washed with brine,
dried over Na2SO4, and concentrated. The crude product was purified
by a column chromatography on silica gel eluted with hexane-EtOAc
(3:1) to give 19 (31.6 mg, 0.0928 mmol, 45%) as a pale oil. 1H NMR
(300 MHz) δ 0.88 (3H, t, J = 7.0 Hz), 1.16–1.41 (18H, m), 1.48–1.69
(4H, m), 1.95–2.11 (2H, m), 2.04 (3H, s), 2.34 (2H, t, J = 7.3 Hz), 5.17
(1H, q, J = 7.0 Hz), 5.36 (1H, m), 5.67 (1H, dt, J = 15.7, 7.0 Hz),
9.75–9.77 (1H, br.). 13C NMR (75 MHz) δ 14.09, 21.42, 22.63, 24.56,
25.18, 28.65, 28.80, 29.07, 29.21, 29.33, 29.46, 31.82, 32.07, 33.99,
34.48, 75.14, 128.45, 134.16, 170.58, 179.93. DART-MS m/z (rel in-
tensity) 281 [M + H-AcOH]+ (42), 89 (100), 61 (38). HR-DART-MS
[M + H-AcOH]+ m/z 281.24687 (calcd for C18H33O2: 281.24805).
The title compound was obtained by alkaline hydrolysis of 13 at rt.
in 78% yield in a similar procedure used for the synthesis of 4. White
crystals, mp 49 °C. 1H NMR (500 MHz) δ 0.89 (3H, t, J = 7.1 Hz),
1.23–1.41 (19H, m), 1.41–1.57 (2H, m), 1.57–1.668 (2H, m), 2.03 (2H,
q, J = 7.1 Hz), 2.34 (2H, t, J = 7.3 Hz), 4.04 (1H, q, J = 6.8 Hz), 5.44
(1H, dd, J = 15.4, 7.1 Hz), 5.63 (1H, dt, J = 15.4, 6.7 Hz), 9.75–9.77
(1H, br.). 13C NMR (125 MHz) δ 14.03, 22.49, 24.65, 25.43, 28.85,
29.00, 29.16, 29.28, 29.46 (×2), 31.34, 32.13, 33.93, 37.26, 73.27,
132.29, 132.89, 179.23. DART-MS m/z (rel intensity) 298 (36), 297
(46), 282 (76), 281 (100). HR-DART-MS m/z [M
281.24863 (calcd for C18H33O2: 281.24806).
+
H-H2O]+
2.8.11. 9-(Tetrahydropyran-2-yl)oxy-1-nonyne (15)
A solution of 14 (1.10 g, 7.83 mmol), dihydro-2H-pyran (1.24 g,
14.7 mmol), and p-TsOH·H2O (0.05 g) in dry CH2Cl2 (60 mL) was
stirred at rt. for 18 h. The mixture was then washed with 5% NaHCO3
solution (30 mL) and the aqueous layer was extracted with CH2Cl2. The
combined organic extracts were washed with brine, dried over Na2SO4,
and concentrated. The oily residue was chromatographed on silica gel
eluted with hexane-Et2O (19:1) to give 15 (1.52 g, 6.76 mmol, 69%) as
a colorless oil. 1H NMR (300 MHz) δ 1.21–1.46 (6H, m), 1.46–1.67 (8H,
m), 1.67–1.90 (2H, m), 1.94 (1H, t, J = 2.6 Hz), 2.18 (2H, dt, J = 6.9,
2.6 Hz), 3.38 (1H, dt, J = 9.5, 6.7 Hz), 3.45–3.56 (1H, m), 3.73 (1H, dt,
2.8.15. (E)-10-Hydroxyoctadec-8-enoic acid (2)
The title compound was obtained by alkaline hydrolysis of 19 at rt.
in 36% yield in a similar procedure used for the synthesis of 1. Pale
yellow crystals, mp 49 °C. 1H NMR (500 MHz) δ 0.88 (3H, t,
J = 6.9 Hz), 1.18–1.58 (19H, m), 1.59–1.72 (3H, m), 2.04 (2H, t,
J = 7.3 Hz), 2.34 (2H, t, J = 7.3 Hz), 3.45–3.73 (2H, br.), 4.04 (1H, q,
J = 6.7 Hz), 5.41–5.48 (1H, m), 5.61 (1H, dt, J = 15.4, 6.9 Hz). 13C
NMR (125 MHz) δ 14.09, 22.65, 24.57, 25.47, 28.26, 28.57, 28.76,
28.82, 29.25, 29.54, 31.86, 32.01, 33.88, 37.28, 73.27, 131.97, 133.12,
179.08. DART-MS m/z (rel intensity) 299 (31), 298 (34), 282 (38), 281
(100), 279 (58). HR-DART-MS [M + H-H2O]+ m/z 281.24670 (calcd
for C18H34O3: 281.24805).
J = 9.5, 7.0 Hz), 3.81 3.94 (1H, m), 4.58 (1H, dd, J = 4.1, 2.8 Hz). 13
C
NMR (75 MHz) δ 18.33, 19.66, 25.44, 26.07, 28.36, 28.63, 28.89,
29.64, 30.72, 62.30, 67.55, 68.06, 84.66, 98.80. DART-MS m/z (rel
intensity) 225 (9), 169 (12), 102 (19), 85 (100). HR-DART-MS m/ z
[M + H]+ 225.18602 (calcd for C14H25O2: 225.18546).
2.8.16. 1,10-Dihydroxyoctadec-8-ene (20)
A solution of 16 (167.7 mg, 0.455 mmol) in MeOH (3 mL) con-
taining a catalytic amount of PPTS was allowed to stand at rt. for 20 h.
After the MeOH had been removed in vacuo, the residue was chroma-
tographed on silica gel eluted with hexane-EtOAc (2:1) to give 20
(59.5 mg, 0.209 mmol, 46%) as a colorless oil. 1H NMR (300 MHz) δ
0.88 (3H, t, J = 7.0 Hz), 1.22–1.62 (25H, m), 1.64–1.71 (1H, m), 2.02
(1H, q, J = 7.0 Hz), 2.21 (1H, dt, J = 7.0, 1.8 Hz), 3.64 (2H, t,
J = 6.7 Hz), 4.03 (1H, q, J = 6.8 Hz), 5.44 (1H, m), 5.62 (1H, dt,
J = 15.2, 6.7 Hz). DART-MS m/z (rel intensity) 284 (18), 283 (33), 281
(25), 267 (71), 265 (100), 249 (38), 247 (31). HR-DART-MS [M + H-
H2O]+ m/z 267.26888 (calcd for C18H35O: 267.26879).
2.8.12. (E)-18-(Tetrahydropyran-2-yl)oxyoctadec-10-en-9-ol (16)
To a solution of 15 (0.758 g, 3.38 mmol) in dry hexane (5 mL), a
1 M toluene solution of DIBAL (3.71 mL, 3.71 mmol) was added
dropwise at rt. under Ar atmosphere, and the mixture was stirred at
60 °C for 2 h. The mixture was then cooled to −78 °C and nonanal
(0.577 mg, 4.06 mmol) dissolved in toluene (4 mL) was added drop-
wise. After 2 h at −60 °C, the reaction mixture was warmed up to rt.,
quenched with water, and acidified with 1 M HCl. The whole was ex-
tracted twice with EtOAc, washed with brine, dried over Na2SO4, and
concentrated. The oily residue was chromatographed on silica gel
eluted with hexane-EtOAc (7:1 to 2:1) gave crude 16 (0.548 g,
1.49 mmol, 44%) as a mixture of diastereomers. DART-MS m/z (rel
intensity) 367 (5), 352 (33), 351 (100), 333 (37), 283 (37), 281 (33), 85
(94).
2.8.17. p-Bromophenacyl ester of oleic acid (25)
A mixture of oleic acid (2.82 g, 10.0 mmol) and K2CO3 (2.28 g,
16.0 mmol) in dry acetone (25 mL) was stirred at rt. for 30 min. p-
Bromophenacy bromide (3.06 g, 11.0 mmol) was then added and the
whole was stirred overnight. The reaction mixture was filtrated and the
filtrate was evaporated. The residue was then extracted with diethyl
ether, washed with 5% NaHCO3 solution, dried over anhydrous
Na2SO4, and concentrated. The crystalline product was recrystallized
from methanol, washed with hexane to remove unreacted oleic acid,
giving 25 as a pale yellow powder. 1H NMR (400 MHz) δ 0.88 (3H, t,
J = 7.3 Hz), 1.17–1.45 (20H, m), 1.70 (2H, m), 1.96–2.08 (4H, m),
2.48 (2H, t, J = 7.3 Hz), 5.28 (2H, s), 5.32–5.38 (2H, m), 7.64 (2H, d,
J = 8.8 Hz), 7.78 (2H, d, J = 8.8 Hz). 13C NMR (100 MHz) δ 14.09,
22.67, 24.85, 27.14, 27.18, 29.03, 29.06, 29.14, 29.29 (×2), 29.49,
29.67, 29.74, 31.87, 33.84, 65.61, 129.05, 129.21 (×2), 129.73,
129.95, 132.18 (×2), 132.94, 173.15, 191.44.
2.8.13. (E)-10-(Acetoxy)octadec-8-en-1-ol (18)
A solution of the crude 16 (0.548 mg, 1.49 mmol) in Ac2O (0.5 mL)
and pyridine (1 mL) was stirred at rt. for 40 h. The reaction was
quenched with water, acidified with 2 M HCl, and extracted twice with
ether. The ethereal extracts were combined, washed with 5% NaHCO3,
dried over Na2SO4, and concentrated. The crude product 17 was dis-
solved EtOH (12 mL) and a catalytic amount of p-TsOH·H2O (0.05 g)
was added. After the mixture had been stirred at rt. for 25 min, it was
concentrated and purified by a column chromatography on silica gel
eluted with hexane-EtOAc (3:1) to give 18 (160 mg, 0.491 mmol, 33%)
as a pale yellow oil. 1H NMR (300 MHz) δ 0.88 (3H, t, J = 6.7 Hz),
1.19–1.44 (20H, m), 1.46–1.68 (4H, m), 1.61 (1H, br. s), 1.96–2.09
4