Organic & Biomolecular Chemistry
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(3 : 1 by 1H NMR spectroscopy). The Wittig reaction was reflux for 9 h, cooled to rt, and concentrated. The residue was
repeated and the products were purified by chromatography washed with Et2O repeatedly to give phosphonium salt 28
on silica gel (hexane/EtOAc). Carbonate 29: Rf = 0.75 (hexane/ (417 mg, 98%), which was used for the next reaction without
EtOAc 1 : 1); 1H NMR (300 MHz, CDCl3) δ 1.04 (t, J = 7.5 Hz, further purification.
3 H), 1.64–1.84 (m, 4 H), 2.05–2.16 (m, 2 H), 2.32 (t, J = 7.4 Hz,
To a solution of the above phosphonium salt 28 in THF
2 H), 2.80 (t, J = 5.4 Hz, 2 H), 2.98 (t, J = 7.2 Hz, 2 H), 3.66 (s, (2 mL) was added NaHMDS (1.0 M in THF, 0.51 mL,
3 H), 4.26 (dt, J = 7.7, 6.5 Hz, 1 H), 4.71 (t, J = 7.7 Hz, 1 H), 0.510 mmol) at −78 °C. After 30 min of stirring at −78 °C, alde-
5.30–5.47 (m, 4 H), 5.53 (dt, J = 11.0, 7.2 Hz, 1 H), 5.64 (dd, J = hyde 32 (50 mg, 0.255 mmol) in THF (1.5 mL) was added drop-
15.0, 7.7 Hz, 1 H), 6.05 (t, J = 11.0 Hz, 1 H), 6.21 (dd, J = 15.0, wise. The mixture was warmed to 0 °C over 3 h and poured
10.8 Hz, 1 H), 6.46 (dd, J = 15.0, 10.8 Hz, 1 H), 6.64 (dd, J = onto a mixture of saturated NH4Cl and EtOAc with vigorous
15.0, 11.0 Hz, 1 H); 13C–APT NMR (75 MHz, CDCl3) δ 9.0 (+), stirring. The resulting mixture was extracted with EtOAc three
24.7 (−), 25.6 (−), 26.0 (−), 26.3 (−), 26.5 (−), 33.4 (−), 51.5 (+), times. The combined extracts were washed with saturated
82.5 (+), 83.2 (+), 125.2 (+), 127.1 (+), 128.0 (+), 128.6 (+), 128.9 NaHCO3, dried over MgSO4 and concentrated to leave a
(+), 129.1 (+), 130.2 (+), 131.5 (+), 132.9 (+), 136.9 (+), 154.4 (−), residue, which was passed through a short column of silica gel
174.0 (−). Diol 30: Rf = 0.49 (hexane/EtOAc 1 : 1); 1H NMR (hexane/EtOAc) to give a mixture of carbonate 33 and diol 34
(400 MHz, CDCl3) δ 0.99 (t, J = 7.4 Hz, 3 H), 1.36–1.50 (m, 1 H), (3 : 2 by 1H NMR spectroscopy). The Wittig reaction was
1.54–1.66 (m, 1 H), 1.70 (quint., J = 7.4 Hz, 2 H), 2.10 (dt, J = repeated and the products were purified by chromatography
6.8, 7.4 Hz, 2 H), 2.24–2.33 (m, 1 H), 2.32 (t, J = 7.4 Hz, 2 H), on silica gel (hexane/EtOAc). Carbonate 33: Rf = 0.74 (hexane/
2.37 (s, 1 H), 2.81 (t, J = 5.6 Hz, 2 H), 2.92–3.00 (m, 2 H), EtOAc 1 : 1); 1H NMR (400 MHz, CDCl3) δ 1.02 (t, J = 7.4 Hz,
3.37–3.45 (m, 1 H), 3.67 (s, 3 H), 4.00 (t, J = 6.8 Hz, 1 H), 3 H), 1.53–1.77 (m, 4 H), 2.10 (q, J = 7.2 Hz, 2 H), 2.31 (t, J =
5.32–5.49 (m, 5 H), 5.70 (dd, J = 15.2, 6.8 Hz, 1 H), 6.04 (t, J = 7.4 Hz, 2 H), 2.80 (t, J = 5.8 Hz, 2 H), 2.97 (t, J = 7.4 Hz, 2 H),
11.2 Hz, 1 H), 6.21 (dd, J = 14.8, 10.8 Hz, 1 H), 6.39 (dd, J = 3.66 (s, 3 H), 4.61 (ddd, J = 9.2, 7.8, 4.8 Hz, 1 H), 5.15 (t, J =
15.2, 10.8 Hz, 1 H), 6.55 (dd, J = 14.8, 11.2 Hz, 1 H); 13C–APT 7.8 Hz, 1 H), 5.32–5.44 (m, 4 H), 5.52 (dt, J = 11.0, 7.4 Hz, 1 H),
NMR (75 MHz, CDCl3) δ 10.1 (+), 24.8 (−), 25.7 (−), 25.9 (−), 5.64 (dd, J = 15.2, 7.8 Hz, 1 H), 6.05 (t, J = 11.0 Hz, 1 H), 6.22
26.3 (−), 26.7 (−), 33.6 (−), 51.7 (+), 75.7 (+), 76.1 (+), 127.5 (+), (dd, J = 14.8, 10.8 Hz, 1 H), 6.45 (dd, J = 15.2, 10.8 Hz, 1 H),
128.5 (+), 128.8 (+), 129.1 (+), 131.1 (+), 132.0 (+), 132.4 (+), 6.63 (dd, J = 14.8, 11.0 Hz, 1 H); 13C–APT NMR (100 MHz,
133.0 (+), 174.4 (−).
CDCl3) δ 10.0 (+), 23.5 (−), 24.8 (−), 25.7 (−), 26.3 (−), 26.6 (−),
To an ice-cold solution of the above mixture in THF (4 mL) 33.5 (−), 51.6 (+), 80.3 (+), 81.6 (+), 122.6 (+), 127.2 (+), 128.1
and MeOH (4 mL) was added 2 N LiOH (2.5 mL, 5.00 mmol). (+), 128.6 (+), 129.0 (+), 129.2 (+), 130.4 (+), 131.3 (+), 132.9 (+),
The mixture was stirred at 0 °C for 5 h and diluted with 136.9 (+), 154.6 (−), 174.1 (−). Diol 34: Rf = 0.48 (hexane/EtOAc
McIlvaine’s phosphate buffer (pH 5.0). The resulting mixture 1 : 1); 1H NMR (400 MHz, CDCl3) δ 0.98 (t, J = 7.4 Hz, 3 H),
was extracted with Et2O three times. The combined extracts 1.36–1.54 (m, 2 H), 1.70 (quint., J = 7.4 Hz, 2 H), 2.06–2.14 (m,
were dried over MgSO4 and concentrated to leave a residue, 3 H), 2.27 (br s, 1 H), 2.32 (t, J = 7.4 Hz, 2 H), 2.80 (t, J = 5.6 Hz,
which was purified by chromatography on silica gel (Et2O) to 2 H), 2.92–2.99 (m, 2 H), 3.58–3.67 (m, 1 H), 3.66 (s, 3 H),
give (18R)-resolvin E3 (132 mg, 78% over two steps), which was 4.13–4.19 (m, 1 H), 5.32–5.48 (m, 5 H), 5.77 (dd, J = 15.2,
further purified by using recycling HPLC (LC-Forte/R equipped 7.0 Hz, 1 H), 6.03 (t, J = 11.2 Hz, 1 H), 6.22 (dd, J = 15.0,
with YMC-Pack SIL-60, hexane/EtOAc 25 : 75, 25 mL min−1): 10.8 Hz, 1 H), 6.37 (dd, J = 15.2, 10.8 Hz, 1 H), 6.54 (dd, J =
liquid; Rf = 0.39 (CH2Cl2/MeOH 10 : 1); [α]2D2 +31 (c 0.19, 15.0, 11.2 Hz, 1 H); 13C–APT NMR (100 MHz, CDCl3) δ 10.3 (+),
MeOH); lit.6 [α]2D5 +34 (c 0.16, MeOH); 1H NMR (400 MHz, 24.8 (−), 25.3 (−), 25.7 (−), 26.3 (−), 26.7 (−), 33.6 (−), 51.7 (+),
CD3OD) δ 0.97 (t, J = 7.4 Hz, 3 H), 1.28–1.42 (m, 1 H), 1.52–1.63 75.4 (+), 75.9 (+), 127.5 (+), 128.5 (+), 128.7 (+), 128.8 (+),
(m, 1 H), 1.67 (quint., J = 7.2 Hz, 2 H), 2.13 (q, J = 7.2 Hz, 2 H), 129.1 (+), 130.9 (+), 131.0 (+), 132.0 (+), 133.4 (+), 174.3 (−).
2.30 (t, J = 7.2 Hz, 2 H), 2.85 (t, J = 5.6 Hz, 2 H), 2.99 (t, J = 5.8
To an ice-cold solution of the above mixture in THF (2 mL)
Hz, 2 H), 3.30–3.38 (m, 1 H), 3.97 (t, J = 6.6 Hz, 1 H), 4.89 (br s, and MeOH (2 mL) was added 2 N LiOH (1.0 mL, 2.00 mmol).
3 H), 5.32–5.46 (m, 5 H), 5.74 (dd, J = 15.0, 6.6 Hz, 1 H), 6.04 (t, The mixture was stirred at 0 °C for 5 h and diluted with
J = 11.2, 1 H), 6.24 (dd, J = 14.8, 10.8 Hz, 1 H), 6.38 (dd, J = McIlvaine’s phosphate buffer (pH 5.0). The resulting mixture
15.0, 10.8 Hz, 1 H), 6.58 (dd, J = 14.8, 11.2 Hz, 1 H); 13C–APT was extracted with Et2O three times. The combined extracts
NMR (75 MHz, CD3OD) δ 10.6 (+), 26.0 (−), 26.6 (−), 27.1 (−), were dried over MgSO4 and concentrated to leave a residue,
27.6 (−), 34.3 (−), 76.6 (+), 77.3 (+), 128.6 (+), 129.2 (+), 129.6 which was purified by chromatography on silica gel (Et2O) to
(+), 129.8 (+), 130.1 (+), 131.2 (+), 133.4 (+), 133.7 (+), 134.3 (+), give (18S)-resolvin E3 (54 mg, 64% over two steps), which was
1
177.1 (−). The H and 13C NMR spectra were identical to those further purified by using recycling HPLC (LC-Forte/R equipped
reported in ref. 6.
with YMC-Pack SIL-60, hexane/EtOAc 25 : 75, 25 mL min−1):
liquid; Rf = 0.44 (CH2Cl2/MeOH 10 : 1); [α]2D3 +11 (c 0.15,
MeOH); lit.6 [α]D27 +7.7 (c 0.15, MeOH); 1H NMR (400 MHz,
CD3OD) δ 0.98 (t, J = 7.4 Hz, 3 H), 1.30–1.44 (m, 1 H), 1.54–1.64
(5Z,8Z,11Z,13E,15E,17R,18S)-17,18-Dihydroxyicosa-
5,8,11,13,15-pentaenoic acid ((18S)-Resolvin E3)
A solution of iodide 46 (234 mg, 0.727 mmol) and PPh3 (m, 1 H), 1.67 (quint., J = 7.2 Hz, 2 H), 2.13 (q, J = 7.2 Hz, 2 H),
(279 mg, 1.06 mmol) in MeCN (3.5 mL) was heated under 2.30 (t, J = 7.2 Hz, 2 H), 2.85 (t, J = 5.6 Hz, 2 H), 2.99 (t, J = 5.8 Hz,
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