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Organic & Biomolecular Chemistry
Page 9 of 11
DOI: 10.1039/C8OB02116C
Journal Name
ARTICLE
(COCl)2 (0.195 mL, 2.27 mmol, 3 equiv) in CH2Cl2 (6 mL) was
slowly added DMSO (2.0 M in CH2Cl2, 2.24 mL, 4.48 mmol, 6
equiv) at −78 °C. A soluꢀon of alcohol 29 (293 mg, 0.731
mmol, 1.0 equiv) in CH2Cl2 (6 mL) was added to the solution
at −78 °C. Aꢁer an addiꢀonal 15 min of sꢀrring at −78 °C, Et3N
(1.10 mL, 7.89 mmol, 11 equiv) was added. After being stirred
at 0 °C for 15 min, the mixture was diluted with saturated
NaHCO3 solution (aq.) and extracted with hexane three times.
The combined organic extracts were dried over MgSO4 and
concentrated. The residue was purified by chromatography
The solution was stirred at rt for 1 h and diluted with
McIlvaine’s phosphate buffer (pH 5.0). The mixture was
extracted with Et2O three times. The combined organic
extracts were dried over MgSO4 and concentrated. The
residue was purified by chromatography on silica gel
(hexane
was further purified by using recycling HPLC (LC-Forte
equipped with YMC-Pack SIL-60, hexane EtOAc 1:1, 20
mL min): white solids; mp 42–43 °C; Rf 0.30 (hexane EtOAc
/EtOAc 2:1) to afford diol 32 (71 mg, 90%), which
/
R
/
/
/
20
1
2:1); [α]D +9.4 (c 0.96, CHCl3); H NMR (400 MHz, CDCl3) δ
0.88 (t, J = 7.2 Hz, 3 H), 1.20–1.55 (m, 8 H), 1.71 (quint., J =
7.6 Hz, 2 H), 1.99 (br s, 1 H), 2.11 (br s, 1 H), 2.12 (q, J = 7.2 Hz,
2 H), 2.33 (t, J = 7.6 Hz, 2 H), 2.93 (t, J = 6.0 Hz, 2 H), 3.67 (s, 3
H), 3.63–3.76 (m, 1 H), 4.10–4.18 (m, 1 H), 5.34–5.48 (m, 3 H),
5.77 (dd, J = 15.2, 7.2 Hz, 1 H), 6.03 (t, J = 11.2 Hz, 1 H), 6.22
(dd, J = 14.8, 10.8 Hz, 1 H), 6.37 (dd, J = 15.2, 10.8 Hz, 1 H),
6.53 (dd, J = 14.8, 11.2 Hz, 1 H); 13C–APT NMR (75 MHz,
CDCl3) δ 14.1 (+), 22.7 (–), 24.8 (–), 25.6 (+), 26.3 (–), 26.7 (–),
31.9 (–), 32.3 (–), 33.5 (–), 51.6 (+), 74.4 (+), 75.7 (+), 128.3 (+),
128.6 (+), 128.8 (+), 129.4 (+), 130.8 (+), 131.1 (+), 132.0 (+),
133.5 (+), 174.2 (–); HRMS (FAB+) calcd for C21H34O4Na
on silica gel (hexane
mg, 93%), which was further purified by using recycling HPLC
(LC-Forte R equipped with YMC-Pack SIL-60, hexane EtOAc
95:5, 20 mL min). Aldehyde 30 (183 mg, 63%); colorless
liquid; Rf 0.55 (hexane
/EtOAc 19:1) to afford aldehyde 30 (271
/
/
/
20
/
EtOAc 9:1); [α]D +0.93 (c 1.05,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 0.02 (s, 3 H), 0.03 (s, 3 H),
0.11 (s, 9 H), 0.87 (s, 9 H), 0.89 (t, J = 6.8 Hz, 3 H), 1.18–1.53
(m, 8 H), 3.61 (dt, J = 6.0, 4.6 Hz, 1 H), 4.08 (t, J = 6.0 Hz, 1 H),
6.14 (dd, J = 15.2, 8.0 Hz, 1 H), 6.31 (dd, J = 15.4, 6.0 Hz, 1 H),
6.41 (dd, J = 15.4, 10.8 Hz, 1 H), 7.11 (dd, J = 15.2, 10.8 Hz, 1
H), 9.57 (d, J = 8.0, 1 H); 13C–APT NMR (100 MHz, CDCl3) δ –
4.6 (+), –4.1 (+), 0.2 (+), 14.0 (+), 18.2 (–), 22.6 (–), 24.6 (–),
25.9 (+), 32.0 (–), 33.8 (–), 75.8 (+), 76.2 (+), 128.6 (+), 131.4
(+), 146.0 (+), 151.7 (+), 193.9 (+); HRMS (FAB+) calcd for
C21H42O3Si2Na [(M+Na)+] 421.2570, found 421.2571.
1
[(M+Na)+] 373.2355, found 373.2363. The H NMR spectrum
was consistent with that reported.17a
(5Z,8Z,10E,12E,14R,15S)-14,15-Dihydroxyicosa-5,8,10,12-
tetraenoic acid (14R,15S-diHETE) (22). To a solution of diol
32 (9.3 mg, 0.0265 mmol, 1.0 equiv) in MeOH (0.2 mL) and
H2O (0.1 mL) was added LiOH·H2O (10.4 mg, 0.248 mmol, 9
equiv). After 1 h of stirring at rt, McIlvaine’s phosphate buffer
(pH 5.0) was added. The resulting mixture was extracted with
Et2O three times. The combined organic extracts were dried
over MgSO4 and concentrated. The residue was purified by
Methyl
(5Z,8Z,10E,12E,14R,15S)-15-[(tert-
butyldimethylsilyl)oxy]-14-[(trimethylsilyl)oxy]icosa-
5,8,10,12-tetraenoate (31). To an ice-cold solution of
phosphonium salt 24 (561 mg, 1.13 mmol, 2.7 equiv) in THF
(2 mL) was added NaHMDS (1.0 M in THF, 1.00 mL, 1.00
mmol, 2.3 equiv) dropwise. The mixture was stirred at 0 °C
for 1 h and cooled to –78 °C. A solution of aldehyde 30 (170
mg, 0.426 mmol, 1.0 equiv) in THF (2 mL) was added to the
mixture, which was then warmed to rt over 1 h and diluted
with saturated NH4Cl solution (aq.). The resulting mixture was
extracted with hexane three times. The combined organic
extracts were dried over MgSO4 and concentrated. The
residue was purified by chromatography on silica gel
chromatography on silica gel (hexane/EtOAc 1:2) to afford
14R,15S-diHETE (22) (7.1 mg, 80%): white solids; mp 58–59
20
°C; Rf 0.35 (hexane/EtOAc 1:2); [α]D +26 (c 0.71, CHCl3); UV
1
(MeOH) λmax 263, 273, 284 nm (ε 40000, 53000, 42000); H
NMR (400 MHz, CD3OD) δ 0.91 (t, J = 6.8 Hz, 3 H), 1.22–1.60
(m, 8 H), 1.66 (quint., J = 7.2 Hz, 2 H), 2.14 (q, J = 7.2 Hz, 2 H),
2.30 (t, J = 7.2 Hz, 2 H), 2.96 (t, J = 6.0 Hz, 2 H), 3.44–3.52 (m,
1 H), 3.96 (t, J = 6.6 Hz, 1 H), 4.64 (br s, 3 H), 5.32–5.47 (m, 3
H), 5.79 (dd, J = 14.8, 6.6 Hz, 1 H), 6.02 (t, J = 11.2 Hz, 1 H),
6.24 (dd, J = 14.8, 10.8 Hz, 1 H), 6.36 (dd, J = 14.8, 10.8 Hz, 1
H), 6.57 (dd, J = 14.8, 11.2 Hz, 1 H); 13C–APT NMR (75 MHz,
CD3OD) δ 11.4 (+), 20.7 (–), 23.0 (–), 23.7 (+), 24.1 (–), 24.5 (–),
30.1 (–), 30.8 (–), 31.3 (–), 72.7 (+), 73.9 (+), 126.0 (+), 126.4
(+), 126.8 (+), 127.4 (+), 128.2 (+), 130.5 (+), 130.8 (+), 131.1
(+), 174.5 (–); HRMS (FAB+) calcd for C20H31O4 [(M–H)+]
335.2222, found 335.2220.
(hexane
/
EtOAc 19:1) to afford olefin 31 (200 mg, 87%):
colorless liquid; Rf 0.65 (hexane
/
EtOAc 9:1); [α]D20 –13 (c 1.31,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 0.03 (s, 6 H), 0.09 (s, 9 H),
0.87 (s, 9 H), 0.88 (t, J = 6.8 Hz, 3 H), 1.18–1.49 (m, 8 H), 1.71
(quint., J = 7.2 Hz, 2 H), 2.12 (q, J = 7.2 Hz, 2 H), 2.33 (t, J = 7.2
Hz, 2 H), 2.93 (t, J = 6.4 Hz, 2 H), 3.54–3.60 (m, 1 H), 3.67 (s, 3
H), 3.96 (dd, J = 7.2, 4.4 Hz, 1 H), 5.33–5.46 (m, 3 H), 5.67–
5.77 (m, 1 H), 6.03 (t, J = 11.2 Hz, 1 H), 6.13–6.26 (m, 2 H),
6.40–6.51 (m, 1 H); 13C–APT NMR (75 MHz, CDCl3) δ –4.5 (+),
–3.9 (+), 0.5 (+), 14.2 (+), 18.4 (–), 22.7 (–), 24.8 (–), 24.9 (–),
26.1 (+), 26.2 (–), 26.7 (–), 32.2 (–), 33.5 (–), 33.8 (–), 51.6 (+),
76.5 (+), 76.8 (+), 127.4 (+), 128.6 (+), 128.9 (+), 129.4 (+),
130.2 (+), 131.6 (+), 132.9 (+), 134.7 (+), 174.2 (–); HRMS
(FAB+) calcd for C30H55O4Si2 [(M–H)+] 535.3639, found
535.3616.
(S,Z)-tert-Butyldimethyl[(1-(trimethylsilyl)oct-1-en-3-
yl)oxy]silane [(S)-13a]. The conversion of racemic 7a to 13a
was repeated with (S)-7a. In brief, alcohol (S)-7a (1.01 g, 5.09
mmol, 1.0 equiv) in MeOH (3 mL) was added to a mixture of
Ni(OAc)2·4H2O (1.51 g, 6.07 mmol, 1.2 equiv), NaBH4 (223 mg,
5.89 mmol, 1.2 equiv) and ethylenediamine (0.680 mL, 10.1
mmol, 2.0 equiv) in MeOH (8 mL) under hydrogen, the
mixture was stirred at rt for 5 h to afford allylic alcohol (S)-
12a (890 mg, 88%). A solution of (S)-12a (1.04 g, 5.19 mmol,
1.0 equiv), TBDMSCl (913 mg, 6.06 mmol, 1.2 equiv) and
Methyl (5Z,8Z,10E,12E,14R,15S)-14,15-dihydroxyicosa-
5,8,10,12-tetraenoate (32). To an ice-cold solution of ether
31 (121 mg, 0.225 mmol, 1.0 equiv) in THF (1 mL) was added
TBAF (1.0 M in THF, 1.79 mL, 1.79 mmol, 8 equiv) dropwise.
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