reduced pressure. To the resulting residue was diluted with H2O
(10.0 mL). The solution was cooled to 0 °C and added 6 N HCl
(2.5 mL) dropwise (pH = 3). The organic layer was extracted
with EtOAc (3 × 20 mL), the combined organic layers were
washed with brine and dried over anhydrous Na2SO4. The
solvents were evaporated under reduced pressure to obtain the
crude carboxylic acid, which was directly used for the next step
without further purification.
5.29 (m, 3H), 3.14 (t, J = 7.3 Hz, 2H), 2.76 (t, J = 7.2 Hz, 2H),
2.65 (q, J = 7.5 Hz, 2H), 2.58 – 2.52 (m, 2H), 2.05 (dt, J = 13.9,
7.0 Hz, 2H), 1.59 (p, J = 7.6 Hz, 2H), 1.42 – 1.31 (m, 4H). 13C
NMR (100 MHz, CDCl3): 142.4, 137.3 (2C), 130.7, 130.6 (2C),
130.5, 128.1, 127.3, 90.6, 35.4, 31.5, 31.2, 29.4, 28.8, 27.2, 25.8,
5.2.
[12-(4-Iodo-phenyl)-dodeca-3,6-dienyl]-triphenyl-phosphonium
iodide (55). Yield: 96%. HRMS (ESI) m/z calcd for [C36H39IP]+,
629.1829; found 629.1885. 1H NMR (400 MHz, CDCl3): δ 7.87 –
7.79 (m, 9H), 7.84 – 7.78 (m, 6H), 7.58 (d, J = 8.3 Hz, 2H), 6.92
(d, J = 8.1 Hz, 2H), 5.65 – 5.55 (m, 1H), 5.43 – 5.28 (m, 2H),
5.23 – 5.13 (m, 1H), 3.91 – 3.80 (m, 2H), 2.56 – 2.43 (m, 6H),
1.88 (q, J = 6.9 Hz, 2H), 1.58 – 1.51 (m, 2H), 1.32 – 1.26 (m,
4H). 13C NMR (100 MHz, CDCl3): 142.3, 137.3 (2C), 135.1
(3C), 133.8 (6C), 130.7 – 130.4 (10C), 126.9, 126.2, 118.1 (3C),
90.6, 35.4, 31.1, 29.3, 28.8, 27.1, 25.6, 23.4, 20.4.
A 1.0 M solution of TBAF in THF (1.32 mL, 1.32 mmol) and
two drops of acetic acid were added to a solution of carboxylic
acid (500 mg) in dry THF (10 mL) at rt. The mixture was stirred
at 50 °C, for 10 h. After reaction was completed, THF was
removed in vacuo, the mixture was diluted with EtOAc (15 mL).
The combined organic layers were washed with brine, and the
mixture was extracted with EtOAc (3 × 20 mL). The organic
extracts were dried over Na2SO4 and concentrated in vacuo. The
crude residue was purified by silica gel column chromatography
using 70% EtOAc/hexane to afford compound 52 (256 mg, 75%
over two steps) as a highly viscous colorless liquid. HRMS (ESI)
5-(tert-Butyl-diphenyl-silanyloxy)-20-(4-iodo-phenyl)-icosa-
6,8,11,14-tetraenoic acid methyl ester (56). Yield: 98%. HRMS
(ESI) m/z calcd for [C43H55IO3Si+H]+, 775.3038; found
1
m/z calcd for [C32H43N3O3+H]+: 518.3383; found, 518.3502. H
1
755.0714. H NMR (400 MHz, CDCl3): δ 7.73 – 7.60 (m, 4H),
NMR (400 MHz, CDCl3): δ 7.3 (d, J = 8.0 Hz, 2H), 7.1 (d, J =
8.0 Hz, 2H), 6.5 (dd, J = 15.0, 11.4 Hz, 1H), 6.0 (t, J = 10.4 Hz,
1H), 5.68 (dd, J = 15.3, 6.6 Hz, 1H), 5.45-5.32 (m, 5H), 4.22-
4.17 (m, 1H), 3.34 (t, J = 6.6 Hz, 2H), 2.95 (t, J = 5.8 Hz, 2H),
2.80 (t, J = 6.1 Hz, 2H), 2.58 (t, J = 7.4 Hz, 2H), 2.48-2.39 (m,
4H), 2.07-2.04 (m, 2H), 1.82-1.33 (m, 14H). 13C NMR (100
MHz, CDCl3): 178.7, 142.6, 136.4, 131.5, 130.6, 130.3, 128.9
(2C), 128.3, 128.2, 127.7, 127.5 (2C), 125.2, 120.9, 88.5, 81.3,
71.8, 35.7, 31.2, 29.7, 29.5, 28.9, 28.0, 27.2, 26.1, 25.9, 25.7,
25.2, 20.9, 20.2, 19.0. IR (cm-1): 2926, 2855, 2094 (N3, azide),
1730 (C=O, carboxyl), 1554, 1510, 1456.
7.60 – 7.55 (m, 2H), 7.40 – 7.33 (m, 6H), 6.91 (d, J = 8.2 Hz,
2H), 6.16 (dd, J = 15.0, 11.2 Hz, 1H), 5.87 (t, J = 11.1 Hz, 1H),
5.58 (dd, J = 15.0, 6.8 Hz, 1H), 5.41 – 5.26 (m, 5H), 4.21 (q, J =
6.0 Hz, 1H), 3.62 (s, 3H), 2.81 – 2.74 (m, 4H), 2.57 – 2.50 (m,
2H), 2.18 (t, J = 7.1 Hz, 2H), 2.03 (q, J = 6.6 Hz, 2H), 1.61 –
1.50 (m, 6H), 1.42 – 1.29 (m, 4H), 1.06 (s, 9H). 13C NMR (100
MHz, CDCl3): 173.9, 142.4, 137.2 (2C), 135.9 (4C), 135.7, 134.2
(2C), 130.5 (2C), 130.2, 129.5 (3C), 128.7, 128.1, 127.7, 127.6,
127.4 (4C), 125.4, 90.5, 73.7, 51.4, 37.2, 35.4, 34.0, 31.2, 29.4,
28.8, 27.1, 27.1 (3C), 26.0, 25.6, 20.1, 19.4.
Methyl (S,6E,8Z,11Z,14Z)-20-(4-(6-azidohex-1-yn-1-yl)phenyl)-
5-((tert-butyldiphenylsilyl)oxy)icosa-6,8,11,14-tetraenoate (51).
Yield: 64%. HRMS (ESI) m/z calcd for [C48H63N3O3Si+H]+,
Synthesis of 53, 54, and 56. These compounds were
synthesized as described above.
1
6-(4-Iodo-phenyl)-hexanal (53). Yield: 88%. HRMS (ESI) m/z
770.4711; found 770.5009. H NMR (400 MHz, CDCl3): 7.68 –
1
calcd for [C12H15IO+H]+, 303.0240; found 302.9735. H NMR
7.61 (m, 4H), 7.41 – 7.33 (m, 6H), 7.29 (d, J = 8.0 Hz, 2H), 7.08
(d, J = 7.9 Hz, 2H), 6.16 (dd, J = 15.0, 11.2 Hz, 1H), 5.87 (t, J =
11.1 Hz, 1H), 5.58 (dd, J = 15.0, 6.9 Hz, 1H), 5.39 – 5.28 (m,
5H), 4.21 (q, J = 6.1 Hz, 1H), 3.63 (s, 3H), 3.34 (t, J = 6.7 Hz,
2H), 2.81 – 2.74 (m, 4H), 2.57 (t, J = 7.6 Hz, 2H), 2.45 (t, J = 6.8
Hz, 2H), 2.18 (t, J = 7.2 Hz, 2H), 2.03 (q, J = 7.0 Hz, 2H), 1.79
(dt, J = 14.2, 6.7 Hz, 2H), 1.68 (dt, J = 14.1, 6.6 Hz, 2H), 1.60 –
1.48 (m, 6H), 1.42 – 1.29 (m, 4H), 1.06 (s, 9H). 13C NMR (100
MHz, CDCl3): 173.9, 142.6, 136.0 (4C), 135.7, 134.2 (2C), 131.4
(2C), 130.3, 129.6, 129.5 (4C), 128.7, 128.3 (2C), 128.1, 127.7,
127.6, 127.5, 127.4, 125.5, 120.9, 88.4, 81.3, 73.7, 51.4, 51.1,
37.2, 35.8, 34.0, 31.2, 29.5, 28.9, 28.0, 27.2, 27.1 (3C), 26.0,
25.9, 25.6, 20.1, 19.4, 19.0.
(400 MHz, CDCl3): δ 9.76 (s, 1H), 7.59 (d, J = 8.0 Hz, 2H), 6.92
(d, J = 7.9 Hz, 2H), 2.55 (t, J = 7.7 Hz, 2H), 2.42 (t, J = 7.1 Hz,
2H), 1.69 – 1.32 (m, 4H), 1.41 – 1.30 (m, 2H). 13C NMR (100
MHz, CDCl3): 202.6, 142.0, 137.3 (2C), 130.5 (2C), 90.7, 43.79,
35.2, 31.0, 28.6, 21.9.
tert-Butyl-[12-(4-iodo-phenyl)-dodeca-3,6-dienyloxy]-dimethyl-
silane (54). Yield: 56%. HRMS (ESI) m/z calcd for
[C24H39IOSi+H]+, 499.1888; found 499.1250. 1H NMR (400
MHz, CDCl3): δ 7.58 (d, J = 8.2 Hz, 2H), 6.92 (d, J = 8.2 Hz,
2H), 5.48 – 5.32 (m, 4H), 3.61 (t, J = 7.0 Hz, 2H), 2.78 (t, J = 5.9
Hz, 2H), 2.57 – 2.52 (m, 2H), 2.34 – 2.25 (m, 2H), 2.07 – 2.00
(m, 2H), 1.60 – 1.54 (m, 2H), 1.38 – 1.31 (m, 4H), 0.90 (s, 9H),
0.06 (s, 6H). 13C NMR (100 MHz, CDCl3): 142.4, 137.3 (2C),
130.6 (2C), 130.1, 129.9, 128.0, 126.0, 90.5, 62.9, 35.4, 31.2,
31.2, 29.5, 28.8, 27.1, 26.0 (3C), 25.8, 18.4, −5.2 (2C).
(S,6E,8Z,11Z,14Z)-20-(4-(6-aminohex-1-yn-1-yl)phenyl)-5-
hydroxyicosa-6,8,11,14-tetraenoic acid (57). To a stirred
solution of 52 (105 mg, 0.203 mmol) in THF (10 mL) was added
2 drops of water and TPP (266 mg, 1.01 mmol). The reaction
mixture was kept at rt for 24 h. The reaction mixture was
concentrated under reduced pressure and dried using anhydrous
benzene. The residue was purified by silica gel chromatography
using 15% MeOH/CH2Cl2 as eluent to afford the compound 57
(77.0 mg, 80%) as viscous liquid. Yield: 60%, 114 mg. HRMS
(ESI) m/z calcd for [C32H45NO3−H2O]+: 474.3367; found,
12-(4-Iodo-phenyl)-dodeca-3,6-dien-1-ol (54 step c). Yield:
60%. HRMS (ESI) m/z calcd for [C18H25IO+H]+, 385.1023;
1
found 385.0617. H NMR (400 MHz, CDCl3): δ 7.58 (d, J = 8.3
Hz, 2H), 6.92 (d, J = 8.1 Hz, 2H), 5.53 (q, J = 7.9 Hz, 1H), 5.46 –
5.28 (m, 3H), 3.65 (t, J = 6.4 Hz, 2H), 2.81 (t, J = 7.0 Hz, 2H),
2.54 (t, J = 7.8 Hz, 2H), 2.35 (q, J = 6.7 Hz, 2H), 2.06 (p, J = 6.8
Hz, 2H), 1.58 (p, J = 7.6 Hz, 2H), 1.43 – 1.31 (m, 4H). 13C NMR
(100 MHz, CDCl3): 142.4, 137.3 (2C), 131.5, 130.6 (2C), 130.3,
127.6, 125.4, 90.6, 62.3, 35.4, 31.2, 30.8, 29.4, 28.8, 27.2, 25.8.
1
474.3739. H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.0 Hz,
2H), 7.05 (d, J = 7.2 Hz, 2H) 6.56-6.45 (m, 1H), 6.01-5.91 (m,
1H), 5.71-5.67 (m, 1H), 5.37-5.26 (m, 5H), 4.13 (q, J = 7.3 Hz,
1H), 3.62 (br s, 1H), 3.52-3.42 (m, 2H), 2.82-2.70 (m, 2H), 2.67-
2.60 (m, 2H), 2.40-2.35 (m, 1H), 2.34-2.30 (m, 2H), 2.25-2.20
(m, 2H), 2.09-2.00 (m, 3H), 1.72-1.50 (m, 8H). 1.42-1.12 (m,
8H). 13C NMR (100 MHz, CDCl3): 173.9, 142.6, 134.4 (2C),
1-Iodo-4-(12-iodo-dodeca-6,9-dienyl)-benzene (54 step d).
Yield: 90%. HRMS (ESI) m/z calcd for [C18H24I2+H]+, 495.0040;
1
found 494.9524. H NMR (400 MHz, CDCl3): δ 7.58 (d, J = 8.3
Hz, 2H), 6.93 (d, J = 8.2 Hz, 2H), 5.55 – 5.46 (m, 1H), 5.43 –