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8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=17.4 (q), 31.7 (t), 55.2
(q), 56.0 (q), 57.9 (t), 65.3 (t), 71.9 (t), 78.4 (d), 113.7 (d), 128.3 (d),
128.86 (d), 128.89 (d), 129.4 (d), 130.1 (s), 137.3 (s), 159.1 ppm (s);
IR (neat): n˜ =3418 cmÀ1; MS (EI): m/z: 307 [M+ +H]; HRMS (EI): m/z
calcd for C18H27O4 [M+ +H]: 307.1909; found: 307.1905.
segment B (25, 40 mg, 0.085 mmol) in THF (1 mL), cooled to
À788C under argon, and stirred at À788C for 30 min. A solution of
44 (21 mg, 0.073 mmol) in THF (1 mL) was added dropwise and
the resulting solution was stirred at À788C for 3.5 h. The reaction
mixture was quenched with H2O; extracted with Et2O; and the
combined organic layer was washed with brine, dried over MgSO4,
filtered, and concentrated in vacuo to give a crude product, which
was purified by column chromatography on silica gel (AcOEt/
hexane 1:9 to 1:6) to afford 47 as a colorless oil (35 mg, 92%).
(6R)-Methoxymethyl 6-methoxy-10-(4-methoxybenzyloxy)-2,5-di-
methyldeca-2,4,8-trienoate (39): MnO2 (438 mg, 4.6 mmol) was
added to a solution of alcohol 35 (70 mg, 0.23 mmol) in benzene
(5 mL) and stirred at 508C for 50 min. The reaction mixture was fil-
tered through a pad of Celite and concentrated in vacuo to give
crude product 40, which was used without further purification.
tBuLi (0.31 mL, 0.53 mmol, 1.7m in pentane) was added to a solu-
tion of ethyl dibromopropionate[40] (34 mg, 0.13 mmol) in THF
(0.5 mL), cooled to À788C under argon, and stirred at À788C for
15 min and then stirred at 08C for 30 min. A solution of crude alde-
hyde 40 (20 mg, 0.066 mmol) in THF (1 mL) was added and the re-
sulting mixture was stirred at RT for 75 min and then MOMCl
(25 mL, 0.33 mmol) was added at 08C. After being stirred at RT for
2 h, the reaction mixture was quenched with a saturated solution
of NH4Cl; extracted with Et2O; and the combined organic layer was
washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo to give a crude product, which was purified by column chro-
matography on silica gel (AcOEt/hexane 1:8 to 1:7) to afford 39 as
a pale yellow oil (20 mg, 75%). [a]2D4 = +52.0 (c=1.0, CHCl3);
1H NMR (600 MHz, CDCl3): d=1.83 (s, 3H), 1.97 (s, 3H), 2.25 (ddd,
J=7.2, 8.0, 14.4 Hz, 1H), 2.48 (ddd, J=7.2, 7.2, 14.4 Hz, 1H), 3.21 (s,
3H), 3.48 (s, 3H), 3.80 (s, 3H), 4.04 (d, J=6.8 Hz, 2H), 4.31 (dd, J=
7.2, 7.2 Hz, 1H), 4.43 (s, 2H), 5.32 (s, 2H), 5.48–5.74 (m, 2H), 6.37 (d,
J=12.4 Hz, 2H), 6.87 (d, J=8.8 Hz, 2H), 7.26 (d, J=8.8 Hz, 2H),
7.58 ppm (d, J=12.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=12.2
(q), 18.7 (q), 32.0 (t), 55.2 (q), 56.4 (q), 57.5 (q), 65.4 (t), 71.8 (t), 78.3
(d), 90.5 (t), 113.7 (d), 124.9 (d), 126.2 (s), 128.2 (d), 128.6 (d), 129.4
(d), 130.3 (s), 132.8 (d), 146.0 (s), 159.1 (s), 167.9 ppm (s); IR (neat):
n˜ =1711 cmÀ1; MS (EI): m/z: 404 [M+]; HRMS (EI): m/z calcd for
C23H32O6 [M+]: 404.2199; found: 404.2191.
1
[a]2D2 = +73.4 (c=1.4, CHCl3); H NMR (400 MHz, CDCl3): d=0.98 (d,
3H, J=6.8 Hz), 1.27 (s, 12H), 1.85 (s, 3H), 1.94 (ddd, J=7.2, 7.2,
13.6 Hz, 1H), 1.97 (s, 3H), 2.0–2.16 (m, 5H), 2.23 (ddd, J=6.8, 6.8,
13.6 Hz, 1H), 2.38 (ddd, J=7.2, 7.6, 14.4 Hz, 1H), 2.60 (ddd, J=6.8,
7.2, 14.4 Hz, 1H), 3.22 (s, 3H), 3.48 (s, 3H), 4.34 (dd, J=6.8, 7.6 Hz,
1H), 5.20 (ddd, J=7.2, 7.2, 11.2 Hz, 1H), 5.33 (s, 2H), 5.35–5.42 (m,
3H), 5.68 (dt, J=6.8, 15.2 Hz, 1H), 6.00 (dd, J=11.2, 11.2 Hz, 1H),
6.27 (dd, J=11.2, 15.2 Hz, 1H), 6.38 (d, J=12.4 Hz, 1H), 6.56 (dd,
J=6.8, 18.0 Hz, 1H), 7.59 ppm (d, J=12.4 Hz, 1H); 13C NMR
(150 MHz, CDCl3): d=12.2 (q), 18.6 (q), 18.7 (q), 24.7 (q), 32.0 (t),
32.4 (t), 33.0 (t), 39.1 (t), 39.4 (d), 56.4 (q), 57.5 (q), 78.4 (d), 83.0 (s),
90.5 (t), 124.1 (d), 124.9 (d), 125.0 (d), 125.5 (d), 126.1 (s), 128.7 (d),
130.6 (d), 131.1 (d), 133.0 (d), 135.1 (d), 146.2 (s), 159.4 (d),
168.0 ppm (s); IR (neat): n˜ =1713, 1635, 1362 cmÀ1; MS (FAB): m/z:
551 [M+ +Na]; HRMS (FAB): m/z calcd for C31H49BNaO6 [M+ +Na]:
551.3520; found: 551.3516.
(6R,17S)-Bis(methoxymethyl)
20-(2-hydroxyethyl)-6-methoxy-
2,5,17-trimethyldocosa-2,4,8,10,14,18,20-heptaenedioate (48): A
solution of segment A (11, 73 mg, 0.26 mmol) in MeOH (2 mL) was
added to a solution of [PdCl2(PPh3)2] (18 mg, 0.026 mmol) in MeOH
(1 mL) at RT and stirred for 10 min. NEt3 (0.22 mL, 1.5 mmol) and
a solution of 47 (135 mg, 0.26 mmol) in MeOH (2 mL) were succes-
sively added and the resulting mixture was stirred at RT for 8 h.
The mixture was evaporated to give a crude product, which was
purified by column chromatography on silica gel (AcOEt/hexane
1:3 to 1:1) and HPLC (Kanto Migthysil Si 60 250–10 (5 mm), AcOEt/
hexane 3:2, 5.0 mLminÀ1) to afford 48 as a pale yellow oil (124 mg,
86%). [a]2D4 = +65.0 (c 1.0, CHCl3); 1H NMR (600 MHz, CDCl3): d=
1.04 (d, J=6.0 Hz, 3H), 1.52 (brs, 1H), 1.86 (s, 3H), 1.97 (s, 3H),
2.05 (ddd, J=7.2, 7.2, 13.8 Hz, 1H), 2.08–2.15 (m, 5H), 2.34–2.44
(m, 2H), 2.58 (ddd, J=7.2, 7.8, 13.8 Hz, 1H), 2.58–2.68 (m, 2H), 3.22
(s, 3H), 3.47 (s, 3H), 3.48 (s, 3H), 3.77 (dt, J=6.0, 6.6 Hz, 2H), 4.34
(t, J=7.2 Hz, 1H), 5.20 (dt, J=7.2, 11.4 Hz, 1H), 5.27 (s, 2H), 5.33 (s,
2H), 5.32–5.43 (m, 2H), 5.67 (dt, J=6.6, 15.0 Hz, 1H), 5.70 (s, 1H),
5.99 (dd, J=10.8, 11.4 Hz, 1H), 6.11 (dd, J=7.8, 15.6 Hz, 1H), 6.27
(dd, J=10.8, 15.0 Hz, 1H), 6.38 (d, J=12.0 Hz, 1H), 7.51 (d, J=
15.6 Hz, 1H), 7.59 ppm (d, J=12.0 Hz, 1H); 13C NMR (150 MHz,
CDCl3): d=12.1 (q), 18.7 (q), 19.4 (q), 32.0 (t), 32.2 (t), 32.8 (t), 37.5
(d), 37.6 (t), 39.8 (t), 56.3 (q), 57.5 (q), 61.8 (t), 78.4 (d), 89.8 (t), 90.5
(t), 116.0 (d), 124.2 (d), 124.8 (d), 124.9 (d), 125.5 (d), 126.0 (s), 128.2
(d), 130.6 (d), 131.5 (d), 132.9 (d), 135.0 (d), 145.0 (d), 146.2 (s),
(6R)-Methoxymethyl 10-hydroxy-6-methoxy-2,5-dimethyldeca-
2,4,8-trienoate (43): DDQ (14 mg, 0.060 mmol) was added to a so-
lution of ether 39 (10 mg, 0.025 mmol) in CH2Cl2/H2O (10:1, 0.5 mL)
and stirred at RT for 51 h. The reaction mixture was treated with
a saturated solution of NaHCO3; extracted with CH2Cl2; and the
combined organic layer was washed with brine, dried over MgSO4,
filtered, and concentrated in vacuo to give a crude product, which
was purified by column chromatography on silica gel (AcOEt/
hexane 1:2 to 1:1) to afford 43 as a pale yellow oil (6.0 mg, (84%).
1
[a]2D1 =À17.9 (c=0.84, CHCl3); H NMR (400 MHz, CDCl3): d=1.87 (s,
3H), 1.98 (s, 3H), 2.20 (ddd, J=6.4, 6.4, 14.0 Hz, 1H), 2.58 (ddd, J=
8.0, 8.0, 14.0 Hz, 1H), 3.22 (s, 3H), 3.50 (s, 3H), 4.09 (dd, J=6.8,
12.8 Hz, 1H), 4.21 (dd, J=7.6, 12.8 Hz, 1H), 4.32 (dd, J=6.4, 8.0 Hz,
1H), 5.33 (d, J=9.6 Hz, 1H), 5.36 (d, J=9.6 Hz, 1H), 5.53–5.85 (m,
2H), 6.38 (d, J=12.0 Hz, 1H), 7.59 ppm (d, J=12.0 Hz, 2H);
13C NMR (100 MHz, CDCl3): d=12.1 (q), 18.8 (q), 32.0 (t), 56.5 (q),
57.5 (q), 57.8 (t), 78.1 (d), 90.6 (t), 124.5 (d), 126.2 (s), 128.1 (d),
131.4 (d), 132.8 (d), 146.2 (s), 168.0 ppm (s); IR (neat): n˜ =3435,
1709 cmÀ1; MS (EI): m/z: 284 [M+]; HRMS (EI): m/z calcd for
C15H24O5 [M+]: 284.1624; found: 284.1625.
153.2 (s), 165.4 (s), 168.0 ppm (s); IR (neat): n˜ =3503, 1713 cmÀ1
.
BKA: Acetate buffer (0.75 mL, pH 4), 1-Me-AZADO (0.3 mg,
1.8 mmol), and PhI(OAc)2 (15 mg, 0.046 mmol) were added to a solu-
tion of alcohol 48 (5 mg, 8.9 mmol) in CH2Cl2 (0.75 mL), cooled to
08C under argon, and stirred at RT for 3 h. The reaction mixture
was quenched with a saturated solution of Na2S2O3 at 08C and
stirred for 30 min. The resulting mixture was extracted with Et2O,
and the combined organic layer was washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo to give a crude prod-
uct, which was purified by column chromatography on silica gel
(CHCl3/hexane 1:1) to afford 49 as a pale yellow oil (5.1 mg, 99%).
The monocarboxylic acid (49; 2.3 mg, 3.6 mmol) was dissolved in
THF (0.5 mL) and treated with 6m HCl (0.5 mL) at 08C. The reaction
(6R,17S)-Methoxymethyl 6-methoxy-2,5,17-trimethyl-19-(4,4,5,5-
tetramethyl[1,3,2]dioxaborolan-2-yl)nonadeca-2,4,8,10,14,18-
hexaenoate (47): MnO2 (280 mg, 2.9 mmol) was added to a solu-
tion of alcohol 43 (21 mg, 0.073 mmol) in benzene (2 mL) and
stirred at RT for 1 h. The reaction mixture was filtered through
a pad of Celite and concentrated in vacuo to give crude product
44, which was used without further purification. KHMDS (0.29 mL,
0.15 mmol, 0.5m in toluene) was added dropwise to a solution of
Chem. Eur. J. 2015, 21, 11590 – 11602
11600
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