Zhang et al.
SCHEME 9
1
Methyl 10-HPODE (1c). H NMR (400 MHz, CDCl
3
): δ 7.83
J ) 15.69, 2.09, 1H), 6.33 (dd, J ) 15.77, 0.92, 1H), 3.65 (s, 3H),
2.63 (t, J ) 7.36, 2H), 2.22 (dt, J ) 7.44, 2.75, 2H), 1.10-1.90
(
(
6
6
br, 1H), 5.73 (dt, J ) 15.43, 6.71, 1H), 5.26-5.50 (m, 3H), 4.28
td, J ) 7.51, 6.92, 1H), 3.64 (s, 3H), 2.40 (ddd, J ) 14.98, 7.49,
(m, 16H), 0.86 (t, J ) 7.34, 3H). 13C NMR (75 MHz, CDCl
3
): δ
.51, 1H), 2.27 (t, J ) 7.57, 2H), 2.19 (m, 1H), 2.04 (td, J ) 7.22,
.88, 2H), 1.99 (td, J ) 7.57, 7.39, 2H), 1.58 (m, 2H), 1.19-1.42
200.7, 200.5, 189.4, 174.3, 174.2, 151.3, 151.0, 136.6, 136.6, 134.9,
134.9, 129.6, 129.5, 51.6, 42.2, 42.1, 34.1, 34.0, 32.8, 32.6, 31.4,
30.1, 29.1, 29.0, 28.9, 27.8, 24.9, 24.8, 23.7, 23.5, 22.5, 22.3, 14.0,
(
m, 12H), 0.85 (t, J ) 7.20, 3H). 13C NMR (50 MHz, CDCl
3
,
APT): δ 174.4 (+), 136.8 (-), 132.6 (-), 128.1 (-), 124.0 (-),
6.5 (-), 51.5 (-), 34.1 (+), 32.2 (+), 31.6 (+), 30.7 (+), 29.3
+), 29.1 (+), 29.0 (+), 28.7 (+), 28.7 (+), 27.4 (+), 24.9 (+),
2.6 (+), 14.1 (-). MS: calcd for C19 , 326.2457; HREI
found, 326.2381.
Methyl 12-HPODE (1d). H NMR (400 MHz, CDCl
32 4
13.9. MS: calcd for C19H O , 322.2144; HREI found, 322.2147.
8
(
2
Methyl 10,12-dioxo-ocatadeca-8,13-dienoate (3c) was prepared
by dehydration of 2c by the same procedure as that used to prepare
1
H
34
O
4
3a and 3b. H NMR (600 MHz, CDCl ): δ 6.80 (m, 2H), 5.87
3
(ddt, J ) 15.65, 4.86, 1.54, 2H), 5.47 (s, 1H), 3.60 (s, 3H), 2.24 (t,
J ) 7.54, 2H), 2.16 (dt, J ) 13.96, 7.26, 4H), 1.56 (t, J ) 7.28,
2H), 1.35-1.43 (m, 4H), 1.23-1.32 (m, 6H), 0.84 (t, J ) 7.28,
1
3
): δ 7.93
(
(
6
6
s, 1H), 5.76 (dt, J ) 15.47, 6.85, 1H), 5.27-5.50 (m, 3H), 4.29
3H). 13C NMR (75 MHz, CDCl
): δ 183.9, 183.6, 174.2, 145.4,
145.0, 127.3, 127.2, 99.1, 51.5, 34.1, 32.6, 32.4, 30.4, 28.9, 28.8,
td, J ) 7.78, 7.01, 1H), 3.65 (s, 3H), 2.42 (ddd, J ) 14.33, 7.49,
3
.84, 1H), 2.28 (t, J ) 7.45, 2H), 2.22 (m, 1H), 2.10 (td, J ) 7.43,
.85, 2H), 2.05 (td, J ) 7.63, 6.94, 2H), 1.60 (m, 2H), 1.21-1.42
30 4
28.1, 24.8, 22.3, 13.9. MS: calcd for C19H O , 322.2144; HREI
found, 322.2155.
(
m, 12H), 0.88 (t, J ) 7.15, 3H). 13C NMR (50 MHz, CDCl
3
,
1
APT): δ 174.5 (+), 137.1 (-), 132.4 (-), 127.9 (-), 124.1 (-),
4a+4b. H NMR (300 MHz, CDCl ): δ 7.21 (d, J ) 15.93,
3
8
(
1
3
6.5 (-), 51.5 (-), 34.1 (+), 32.1 (+), 31.2 (+), 30.7 (+), 29.4
1H), 7.04 (dd, J ) 14.52, 6.94, 1H), 6.96 (dd, J ) 15.73, 2.34,
+), 29.3 (+), 29.1 (+), 29.1 (+), 27.4 (+), 25.0 (+), 22.2 (+),
1H), 6.36 (d, J ) 15.85, 1H), 2.65 (t, J ) 7.32, 2H), 2.2-2.4 (m,
4H), 1.1-1.8 (m, 14H), 0.89 (t, J ) 7.31, 3H). 13C NMR (75 MHz,
34 4
4.0 (-). MS: calcd for C19H O , 326.2457; HREI found,
26.2446.
CDCl ): δ 200.7, 200.5, 189.4, 179.0, 178.6, 151.3, 150.9, 136.6,
3
Generation of the Individual 10,13-diHPODE and 9,12-
136.5, 134.9, 134.8, 129.5, 129.4, 42.1, 42.0, 33.8, 33.7, 32.7, 32.6,
diHPODE. They are generated from 10-HPODE and 12-HPODE
31.3, 30.1, 29.7, 29.0, 28.9, 28.8, 27.7, 24.6, 24.5, 23.6, 23.4, 22.4,
22.3, 13.9, 13.8. Those italicized values are for 4b, 9,12-diketo.
MS: calcd for C18H O , 308.1988; HREI found, 308.1994.
28 4
the same way as the mixture of dihydroperoxides.
1
Methyl 10,13-DiHPODE (2a). H NMR (400 MHz, CD
3
OD):
δ 5.6-5.8 (m, 3H), 5.46 (ddt, J ) 15.10, 7.16, 1.45, 1H), 4.72
Conversion of Dihydroperoxides 2a and 2b into Diols 14a
and 14b. Immediately after their purification, the mixture of
dihydroperoxides 2a and 2b was treated with triphenylphosphine
in CH Cl at room temperature for 1 h to generate a mixture of
methyl dihydroxydienoates 13a and 13b that was purified by flash
chromatography on a column that was preconditioned with triethyl-
(dd, J ) 7.34, 6.64, 1H), 4.25 (td, J ) 7.02, 6.46, 1H), 3.64 (s,
3
2
H), 2.30 (t, J ) 7.40, 2H), 2.07 (td, J ) 7.71, 7.16, 2H), 1.59 (m,
H), 1.23-1.46 (m, 12H), 0.89 (t, J ) 6.95, 3H). 13C NMR (50
2
2
MHz, CD
3
OD, APT): δ 176.0 (+), 136.9 (-), 134.7 (-), 132.8
(
3
-), 128.9 (-), 87.4 (-), 86.8 (-), 52.0 (-), 34.8 (+), 33.7 (+),
3.4 (+), 32.9 (+), 30.0 (+), 29.9 (+), 29.8 (+), 26.0 (+), 26.0
amine. The product (R ) 0.17, 6.5 mg, 32%) eluted with 40%
f
+
1
(
-
+), 23.7 (+), 14.4 (-). HRMS (EI): m/z calcd for C19
H O
32 6
(M )
ethyl acetate in hexanes. H NMR (300 MHz, CD OD): δ 5.62
3
OH - H
2
O, 291.2325; found, 291.2323.
Methyl 9,12-DiHPODE (2b). H NMR (400 MHz, CD
(m, 3H), 5.42 (dd, J ) 15.62, 6.59, 1H), 4.50 (dd, J ) 6.37, 5.55,
1H), 4.01 (td, J ) 12.72, 6.15, 1H), 3.64 (s, 3H), 2.30 (t, J ) 7.51,
2H), 2.04 (dd, J ) 14.40, 7.14, 2H), 1.59 (t, J ) 6.76, 2H), 1.20-
1
3
OD):
δ 5.76 (m, 2H), 5.68 (dd, J ) 15.60, 7.48, 1H), 5.55 (dd, J )
1.53 (m, 14H), 0.90 (t, J ) 7.09, 3H). 13C NMR (CD OD, 50 MHz,
1
1
5.55, 7.09, 1H), 4.72 (dd, J ) 12.85, 6.33, 1H), 4.25 (dd, J )
4.35, 6.13, 1H), 3.64 (s, 3H), 2.30 (t, J ) 7.38, 2H), 2.07 (dd, J
3
APT): δ 176.1 (+), 176.0 (+), 134.7 (-), 133.6 (-), 133.1 (-),
132.8 (-), 73.9 (-), 73.1 (-), 52.0 (-), 38.4 (+), 34.8 (+), 33.2
(+), 33.1 (+), 33.0 (+), 32.6 (+), 30.5 (+), 30.4 (+), 30.2 (+),
30.0 (+), 29.8 (+), 26.5 (+), 26.3 (+), 26.1 (+), 26.0 (+), 23.8
(+), 23.3 (+), 14.4 (-), 14.3 (-). MS: calcd for C H O -OH,
)
7
9.43, 7.17, 2H), 1.59 (m, 2H), 1.20-1.50 (m, 12H), 0.90 (t, J )
.29, 3H). 13C NMR (50 MHz, CD
3
OD, APT): δ 176.0 (+), 137.0
(
-), 134.7 (-), 132.9 (-), 128.7 (-), 87.4 (-), 86.8 (-), 52.0
(
3
-), 34.8 (+), 33.7 (+), 33.2 (+), 32.4 (+), 30.5 (+), 30.3 (+),
19
32
4
0.1 (+), 26.6 (+), 26.0 (+), 23.2 (+), 14.3 (-).HRMS (EI): m/z
309.2430; HREI found, 309.2439; for C H O -OH-H O,
1
9
32
4
2
+
calcd for (M ) - OH - H
2
O, 291.2325; found, 291.2306.
291.2324; HREI found, 291.2311. After hydrolysis with PPL, a
Dehydration of Dihydroperoxides 2a and 2b. Acetic anhydride
30 µL) and pyridine (120 µL) were added to a solution of 2a and
mixture of the dihydroxydienoic acids 14a and 14b was obtained.
1
(
2
3
H NMR (300 MHz, CD OD): δ 5.62 (m, 3H), 5.49 (ddt, J )
b (20 mg) in dry CH
2
Cl
2
(2 mL). The resulting mixture was
15.65, 6.57, 1.47 Hz, 1H), 4.53 (dd, J ) 7.00, 5.77 Hz, 1H), 4.04
(1H), 2.27 (t, J ) 7.60 Hz, 2H), 2.08 (td, J ) 8.07, 6.87 Hz, 2H),
allowed to stand at room temperature for 4 h until all of the
dihydroperoxides were consumed. Flash chromatography (15%
1
3
1.62 (m, 2H), 1.27-1.59 (m, 14H), 0.93 (t, J ) 7.09 Hz, 3H).
C
ethyl acetate in hexanes, TLC, R
f
) 0.28) afforded a mixture of 3a
and 3b (10.7 mg, 59%). H NMR (300 MHz, CDCl ): δ 7.18 (dd,
J ) 15.85, 1.07, 1H), 7.02 (dd, J ) 15.85, 2.08, 1H), 6.93 (dd,
3
NMR (50 MHz, CD OD, APT): δ 134.7 (-), 134.6 (-), 133.6
1
3
(-), 133.6 (-), 133.2 (-), 133.1 (-), 132.9 (-), 132.8 (-), 73.9
(-), 73.2 (-), 73.1 (-), 38.4 (+), 35.2 (+), 33.2 (+), 33.1 (+),
5612 J. Org. Chem., Vol. 71, No. 15, 2006