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Organic & Biomolecular Chemistry
Page 8 of 13
DOI: 10.1039/C7OB02291C
ARTICLE
Journal Name
NH4Cl and extracted with EtOAc three times. The combined
organic layers were washed with brine, dried over MgSO4 and
concentrated to give a residue, which was purified by
chromatography on silica gel (hexane/EtOAc 5:1) to afford
alcohol 15 (712 mg, 87%): liquid; Rf = 0.23 (hexane/EtOAc
9:1); IR (neat) 3430, 1459, 1239, 1081 cm–1; 1H NMR (300
MHz, CDCl3) δ 0.63 (q, J = 8.4 Hz, 6 H), 0.91–1.14 (m, 12 H),
1.21 (t, J = 7.2 Hz, 1.5 H) and 1.22 (t, J = 7.2 Hz, 1.5 H), 1.32 (d,
J = 5.1 Hz, 3 H), 1.34–1.48 (m, 1 H), 1.56–1.80 (m, 2 H), 1.80–
1.94 (m, 1 H), 2.62 (br s, 0.5 H) and 2.79 (br s, 0.5 H), 3.30–
3.86 (m, 5 H), 3.93 (dt, J = 7.8, 4.5 Hz, 0.5 H) and 4.09 (dt, J =
7.5, 4.8 Hz, 0.5 H), 4.69 (q, J = 5.1 Hz, 0.5 H) and 4.79 (q, J =
5.1 Hz, 0.5 H); 13C–APT NMR (75 MHz, CDCl3) δ 5.0 (–), 6.8 (+),
11.0 and 11.2 (+), 15.30 and 15.33 (+), 20.2 and 20.7 (+), 21.4
and 21.7 (–), 34.0 and 34.4 (–), 60.3 and 60.6 (–), 60.8 (–),
71.7 and 72.3 (+), 79.8 and 83.3 (+), 99.0 and 107.8 (+); HRMS
(FAB+) calcd for C16H36O4SiNa [(M+Na)+] 343.2281, found
343.2283.
CDCl3) δ 0.59 (q, J = 7.8 Hz, 6 H), 0.88–1.05 (m, 12 H), 1.20 (t, J
= 7.1 Hz, 3 H), 1.31 (d, J = 5.4 Hz, 1.5 H) and 1.32 (t, J = 5.1 Hz,
1.5 H), 1.32–1.46 (m, 1 H), 1.62–1.82 (m, 3 H), 2.02–2.22 (m,
3 H), 2.26–2.42 (m, 3 H), 2.70–2.92 (m, 6 H), 3.26–3.92 (m, 4
H), 3.65 (s, 3 H), 4.69 (q, J = 5.4 Hz, 0.5 H) and 4.77 (q, J = 5.4
Hz, 0.5 H), 5.27–5.55 (m, 8 H); 13C–APT NMR (75 MHz, CDCl3)
δ 5.1 (–), 6.9 (+), 11.1 and 11.2 (+), 15.4 (+), 20.3 and 20.9 (+),
21.5 and 21.9 (–), 24.8 (–), 25.6 (–), 25.7 (–), 25.8 (–), 26.6 (–),
29.2 (–), 29.3 (–), 33.5 (–), 51.5 (+), 59.9 and 60.4 (–), 73.0
and 73.5 (+), 80.2 and 82.5 (+), 99.1 and 100.9 (+), 127.5 (+),
127.9 (+), 128.06 (+), 128.19 (+), 128.23 (+), 128.26 (+), 128.4
(+), 128.6 (+), 128.9 (+), 129.0 (+), 174.1 (–); HRMS (FAB+)
calcd for C31H56O5SiNa [(M+Na)+] 559.3795, found 559.3807.
Methyl (5Z,8Z,11Z,14Z,17S,18S)-18-(1-ethoxyethoxy)-17-
hydroxyicosa-5,8,11,14-tetraenoate (17). To an ice-cooled
solution of 16 (96 mg, 0.18 mmol) in THF (0.6 mL) was added
TBAF (1.0 M in THF, 0.27 mL, 0.27 mmol). The solution was
stirred at 0 °C for 2 h and diluted with brine. The mixture was
extracted with EtOAc three times. The combined extracts
were washed with brine, dried over MgSO4 and concentrated
to leave a residue, which was purified by chromatography on
silica gel (hexane/EtOAc 9:1) to produce alcohol 17 (55 mg,
73%): liquid; Rf = 0.19 and 0.28 (toluene/EtOAc 9:1); IR (neat)
(3S,4S)-4-(1-Ethoxyethoxy)-3-((triethylsilyl)oxy)hexanal (8).
To an ice-cooled flask containing MS4A (740 mg) were added
a solution of alcohol 15 (470 mg, 1.47 mmol) in CH2Cl2 (3 mL)
and NMO (258 mg, 2.20 mmol). The mixture was stirred at
0 °C for 20 min and solid TPAP (52 mg, 0.148 mmol) was
added. After 3 h of stirring at 0 °C, the mixture was diluted
with EtOAc, filtered through a plug of silica gel and eluted
with EtOAc. The combined filtrates ware concentrated to give
a residue, which was purified by chromatography on silica gel
1
3456, 1740, 1438 cm–1; H NMR (300 MHz, CDCl3) δ 0.93 (t, J
= 7.4 Hz, 1.5 H) and 0.95 (t, J = 7.4 Hz, 1.5 H), 1.21 (t, J = 7.1
Hz, 1.5 H) and 1.23 (t, J = 7.1 Hz, 1.5 H), 1.35 (d, J = 5.4 Hz, 1.5
H) and 1.36 (d, J = 5.1 Hz, 1.5 H), 1.36–1.68 (m, 2 H), 1.71
(quint., J = 7.5 Hz, 2 H), 2.06–2.16 (m, 2 H), 2.19–2.38 (m, 4
H), 2.48 (br s, 0.5 H) and 2.50 (br s, 0.5 H), 2.74–2.92 (m, 6 H),
3.28–3.75 (m, 6 H), 4.63 (q, J = 5.4 Hz, 0.5 H) and 4.78 (q, J =
5.4 Hz, 0.5 H), 5.28–5.64 (m, 6 H); 13C–APT NMR (75 MHz,
CDCl3) δ 9.7 (+), 15.27 and 15.33 (+), 20.4 (+), 23.9 (–), 24.2 (–
), 24.8 (–), 25.62 (–), 25.65 (–), 25.86 (–), 25.91 (–), 26.6 (–),
30.9 and 31.3 (–), 33.4 (–), 51.2 (+), 60.9 and 61.6 (–), 71.8
and 72.5 (+), 80.3 (+), 84.3 (+) 100.2 and 101.4 (+), 125.9 (+),
126.0 (+), 128.0 (+), 128.1 (+), 128.20 (+), 128.25 (+), 128.29
(+), 128.8 (+), 129.0 (+), 129.7 (+), 130.2 (+), 174.1 (–); HRMS
(FAB+) calcd for C25H43O5 [(M+Na)+] 423.3110, found
423.3103.
(hexane/EtOAc 14:1) to afford aldehyde
8 (712 mg, 79%):
liquid; Rf = 0.48 (hexane/EtOAc 5:1); IR (neat) 1731, 1459,
1
1128, 1099 cm–1; H NMR (300 MHz, CDCl3) δ 0.61 (q, J = 7.5
Hz, 6 H), 0.95 (t, J = 7.8 Hz, 9 H), 0.99 (t, J = 7.2 Hz, 3 H), 1.20
(t, J = 7.2 Hz, 1.5 H) and 1.21 (t, J = 7.2 Hz, 1.5 H), 1.28 (d, J =
4.8 Hz, 1.5 H) and 1.30 (d, J = 5.1 Hz, 1.5 H), 1.24–1.40 (m, 1
H), 1.64–1.86 (m, 1 H), 2.43–2.74 (m, 2 H), 3.33–3.70 (m, 3 H),
4.36 (quint., J = 4.2 Hz, 0.5 H) and 4.49 (quint., J = 4.2 Hz, 0.5
H), 4.68 (t, J = 5.4 Hz, 0.5 H) and 4.76 (t, J = 5.4 Hz, 0.5 H),
9.78–9.83 (m, 1 H); 13C–APT NMR (75 MHz, CDCl3) δ 4.9 (–),
6.8 (+), 11.0 and 11.1 (+), 15.29 and 15.35 (+), 20.1 and 20.6
(+), 21.60 and 21.67 (–), 46.0 and 46.2 (–), 60.2 and 60.7 (–),
68.0 and 68.8 (+), 79.1 and 81.8 (+), 99.1 and 101.4 (+), 201.9
and 202.1 (+); HRMS (FAB+) calcd for C16H34O4SiNa [(M+Na)+]
341.2124, found 341.2121.
Methyl (5Z,8Z,11Z,14Z,17S,18S)-18-(1-ethoxyethoxy)-17-
((methanesulfonyl)oxy)icosa-5,8,11,14-tetraenoate (6). To
an ice-cooled solution of alcohol 17 (54 mg, 0.13 mmol) in
CH2Cl2 (0.4 mL) were added Et3N (0.36 mL, 2.6 mmol) and
MsCl (0.10 mL, 1.3 mmol). The solution was stirred at 0 °C for
3 h and diluted with saturated NaHCO3. The mixture was
extracted with CH2Cl2 three times. The combined extracts
were washed with brine, dried over MgSO4 and concentrated
to leave a residue, which was purified by chromatography on
Methyl (5Z,8Z,11Z,14Z,17S,18S)-18-(1-ethoxyethoxy)-17-
((triethylsilyl)oxy)icosa-5,8,11,14-tetraenoate (16). To an ice-
cooled suspension of the phosphonium salt
7 (1.07 g, 1.72
mmol) in THF (6 mL) was added NaHMDS (1.0 M in THF, 1.06
mL, 1.06 mmol). The resulting orange mixture was stirred at
0 °C for 1 h, and cooled to –78 °C. A solution of aldehyde
8
(224 mg, 0.705 mmol) in THF (2.3 mL) was added to the
mixture, which was stirred at –78 °C for 5 h and then warmed
to rt before addition of hexane. The resulting mixture was
filtered through a pad of silica gel with hexane/EtOAc (4:1).
silica gel (toluene/EtOAc 9:1) to produce mesylate 6 (55 mg,
85%): liquid; Rf = 0.33 and 0.47 (hexane/EtOAc 4:1); IR (neat)
1738, 1438, 1175, 914 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.97
(t, J = 7.5 Hz, 1.5 H) and 1.01 (t, J = 7.5 Hz, 1.5 H), 1.20 (t, J =
6.9 Hz, 1.5 H) and 1.22 (t, J = 6.9 Hz, 1.5 H), 1.32 (d, J = 5.4 Hz,
1.5 H) and 1.33 (d, J = 5.4 Hz, 1.5 H), 1.42–1.59 (m, 1 H) and
1.68–1.81 (m, 3 H), 2.05–2.17 (m, 2 H), 2.33 (t, J = 7.5 Hz, 2 H),
2.41–2.61 (m, 2 H), 2.74–2.92 (m, 6 H), 3.02 (s, 1.5 H) and
3.03 (s, 1.5 H), 3.41–3.76 (m, 3 H), 3.67 (s, 3 H), 4.62–4.83 (m,
The combined filtrates were dried over MgSO4 and
concentrated to give a residue, which was purified by
chromatography on silica gel (hexane/EtOAc 14:1) to afford
tetraene 16 (318 mg, 84%): liquid; Rf = 0.23 (hexane/EtOAc
14:1); IR (neat) 1741, 1240, 1079 cm–1; 1H NMR (300 MHz,
8 | J. Name., 2012, 00, 1-3
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