Takamura et al.
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δ 139.8, 139.7, 139.5, 134.2, 130.7, 128.5, 128.5, 128.5, 128.3,
127.9, 127.7, 127.5, 127.5, 109.4, 108.1, 97.3, 82.9, 81.8, 77.7,
77.1, 76.9, 75.7, 75.4, 75.3, 75.0, 74.6, 74.5, 73.4, 72.4, 59.9, 55.7,
41.5, 38.8, 37.2, 34.9, 33.2, 32.2, 30.1, 29.6, 29.4, 28.6, 27.9, 27.8,
26.8, 26.7, 26.1, 23.0, 21.1, 18.4, 16.1, 14.3, -5.2, -5.2; HRMS
(ESI) calcd for C62H96O11SiNa (M þ Na)þ 1067.6620, found
1067.6621. (Z)-Alkene 34: colorless oil; Rf = 0.38 (hexane/
colorless oil; Rf = 0.28 (hexane/EtOAc, 2:1); [R]27 þ41.2
D
(c 0.56, CHCl3); IR (neat) 3030, 1733 cm-1 1H NMR
;
(400 MHz, CDCl3) δ 7.35-7.25 (m, 15 H), 4.90 (d, J =
9.5 Hz, 1 H), 4.86-4.82 (m, 2 H), 4.69-4.58 (m, 5 H), 4.38 (d,
J = 12.0 Hz, 1 H), 4.28 (dd, J = 4.7, 2.4 Hz, 1 H), 4.07 (dt, J =
7.3, 4.6 Hz, 1 H), 3.92 (brt, J = 8.8 Hz, 1 H), 3.81-3.78 (m, 2 H),
3.74 (dd, J = 7.6, 2.9 Hz, 1 H), 3.49-3.42 (m, 2 H), 3.49-3.44
(m, 2 H), 3.44 (s, 3 H), 2.51 (dd, J = 15.6, 5.6 Hz, 1 H), 2.40 (dd,
J = 14.2, 9.5 Hz, 1 H), 2.09-1.99 (m, 3 H), 1.85-1.72 (m, 2 H),
1.61-1.42 (m, 4 H), 1.58 (d, J = 1.0 Hz, 3 H), 1.46 (s, 3 H), 1.39
(s, 3 H), 1.37 (s, 3 H), 1.36 (s, 3 H) 1.29-1.23 (m, 10 H), 0.88 (t,
J = 6.8 Hz, 3 H), 0.73 (d, J = 6.6 Hz, 3 H); 13C NMR (100 MHz,
CDCl3) δ 179.3, 138.8, 137.8, 137.7, 132.7, 130.0, 129.4, 128.4,
128.2, 128.2, 128.1, 127.9, 127.4, 127.2, 109.3, 107.7, 97.1, 81.4,
77.2, 76.1, 74.9, 74.8, 74.6, 74.4, 73.4, 71.9, 71.1, 71.0, 60.4, 56.1,
40.5, 39.2, 37.5, 36.1, 32.6, 31.8, 29.7, 29.1, 28.5, 28.2, 27.4, 27.4,
26.5, 26.1, 22.6, 21.4, 21.0, 15.0, 14.2, 14.1; HRMS (ESI) calcd
for C56H80O12Na (M þ Na)þ 967.5547, found 967.5560.
Carboxylic Acid 2. To a solution of tribenzyl ether 35
(15.2 mg, 16.1 μmol) in liquid NH3 (10 mL), THF (5.0 mL),
and t-BuOH (1.0 mL) was added Na (181 mg, 7.86 mmol) at
-78 °C. After the mixture was stirred at the same temperature
for 1 h, the reaction was quenched with saturated aqueous
NH4Cl, and the mixture was allowed to warm to room tem-
perature. The mixture was diluted with H2O and desalted by
passing through the polystyrene gel chromatography (TSK-
G3000S, H2O, aqueous 50% EtOH, EtOH). The aqueous
50% EtOH and EtOH fractions were concentrated to give triol
36 (11.0 mg) as a colorless oil, which was used for the next
reaction without further purification.
EtOAc, 4:1); [R]27D þ17.7 (c 0.96, CHCl3); IR (neat) 2929 cm-1
;
1H NMR (400 MHz, C6D6) δ 7.41-7.37 (m, 5 H), 7.28-7.08 (m,
10 H), 5.18 (d, J = 9.5 Hz, 1 H), 4.81-4.70 (m, 3 H), 4.64 (q, J =
5.8 Hz, 1 H), 4.56 (t, J = 6.8 Hz, 2 H), 4.51-4.46 (m, 2 H), 4.16
(brt, J = 8.6 Hz, 1 H), 4.10-4.05 (m, 1 H), 4.02-3.98 (m, 2 H),
3.93-3.89 (m, 2 H), 3.86-3.78 (m, 2 H), 3.74-3.69 (m, 1 H),
3.66-3.59 (m, 2 H), 3.18 (s, 3 H), 2.77-2.71 (m, 1 H), 2.64 (dd,
J = 14.0, 9.4 Hz, 1 H), 2.54 (dd, J = 14.0, 3.4 Hz, 1 H), 2.20-2.15
(m, 1 H), 2.07 (t, J = 12.2 Hz, 1 H), 1.95 (s, 3 H), 1.92-1.74 (m,
3 H), 1.67-1.49 (m, 3 H), 1.52 (s, 3 H), 1.47 (s, 3 H), 1.45 (s, 3 H),
1.34 (s, 3 H), 1.31-1.24 (m, 10 H), 0.98 (s, 9 H), 0.95 (d, J =
6.4 Hz, 3 H), 0.89 (t, J = 6.4 Hz, 3 H), 0.05 (s, 3 H), 0.05 (s, 3 H);
13C NMR (100 MHz, C6D6); δ 139.8, 139.6, 139.5, 133.8, 132.0,
128.5, 128.5, 128.5, 127.9, 127.7, 127.6, 127.5, 109.4, 108.1, 97.4,
83.4, 81.8, 77.6, 77.2, 77.2, 76.6, 75.7, 75.6, 75.5, 75.4, 74.7, 73.5,
72.6, 60.0, 55.9, 39.1, 37.0, 35.1, 33.8, 33.2, 32.3, 30.2, 29.8, 29.3,
28.6, 27.9, 27.9, 26.9, 26.9, 26.3, 25.0, 23.2, 21.2, 18.6, 14.4, -5.0,
-5.0; HRMS (ESI) calcd for C62H96O11SiNa (M þ Na)þ
1067.6620, found 1067.6621.
Carboxylic Acid 35. To a solution of TBS ether 33 (15.2 mg,
14.5 μmol) in THF (0.50 mL) was added TBAF (1.0 M in THF,
0.10 mL, 0.10 mmol) at room temperature. After the mixture
was stirred at the same temperature for 4 h, the mixture was
poured into Et2O, washed with H2O and brine, and dried over
MgSO4. Concentration and column chromatography (hexane/
EtOAc, 3:1) gave the corresponding alcohol (13.6 mg, quant.):
colorless oil; Rf = 0.39 (hexane/EtOAc, 2:1); [R]27D þ64.5 (c 0.36,
CHCl3); IR (neat) 3502, 2930 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.37-7.27 (m, 15 H), 4.94 (d, J = 9.5 Hz, 1 H), 4.86-4.75 (m,
2 H), 4.69-4.67 (m, 2 H), 4.59 (d, J = 3.9 Hz, 1 H), 4.56 (d, J =
4.4 Hz, 1 H), 4.43 (d, J = 11.7 Hz, 1 H), 4.29 (dd, J = 4.9, 2.9 Hz,
1 H), 3.87-3.77 (m, 4 H), 3.69 (dd, J = 10.3, 3.2 Hz, 1 H), 3.60-
3.36 (m, 7 H), 3.43 (s, 3 H), 2.42 (dd, J = 14.2, 9.5 Hz, 1 H), 2.13-
2.02 (m, 2 H), 1.81-1.74 (m, 1 H), 1.71-1.63 (m, 1 H), 1.59-1.43
(m, 6 H), 1.57 (s, 3 H), 1.52 (s, 3 H), 1.38 (s, 3 H), 1.37 (s, 3 H), 1.35
(s, 3 H), 1.29-1.22 (m, 10 H), 0.88 (t, J = 7.1 Hz, 3 H), 0.75 (d,
J = 6.6 Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ 138.4, 138.4,
133.3, 130.8, 128.7, 128.4, 128.4, 128.4, 128.3, 128.1, 127.7, 127.7,
109.5, 108.0, 97.0, 81.4, 80.6, 78.8, 76.3, 75.9, 74.9, 74.7, 74.7, 74.6,
74.5, 74.5, 73.5, 71.3, 59.9, 56.2, 41.3, 36.7, 36.3, 33.9, 32.6, 31.8,
29.7, 29.1, 28.6, 28.1, 27.5, 27.3, 26.5, 26.0, 22.6, 21.2, 15.9, 14.1;
HRMS (ESI) calcd for C56H82O11Na (M þ Na)þ 953.5755,
found 953.5742.
A solution of triol 36 obtained above in H2O-TFA (3:1,
0.50 mL) was heated to 40 °C and stirred at the same temperature
for 24 h. The mixture was concentrated to give the mixture of
carboxylic acid 2 and its corresponding lactone (9.0 mg) as a
colorless oil, which was used for the next reaction without further
purification.
A solution of the mixture of carboxylic acid 2 and its
corresponding lactone obtained above in MeOH (0.60 mL)
and aqueous KOH (1.0 M, 0.30 mL) was heated to 30 °C and
stirred at the same temperature for 14 h. The resultant mixture
was diluted with H2O and desalted by passing through poly-
styrene gel column chromatography (TSK-G3000S, H2O, aqu-
eous 50% EtOH, EtOH), and the aqueous 50% EtOH and
EtOH fractions were concentrated. The residue was purified by
column chromatography (ODS, aqueous 30% to 50% MeOH)
to give carboxylic acid 2 (8.4 mg, 95% in three steps): colorless
oil; Rf = 0.32 (ODS, aqueous 70% MeOH); [R]23 þ10.6
D
1
(c 0.05, CH3OH); IR (neat) 3406, 2925, 1633, 1576 cm-1; H
NMR (800 MHz, CD3OD) δ 5.08 (d, J = 9.2 Hz, 1 H), 4.04 (dd,
J = 11.5, 6.0 Hz, 1 H), 3.90 (t, J = 3.7 Hz, 1 H), 3.89 (t, J =
6.9 Hz, 1 H), 3.74 (td, J = 10.0, 1.8 Hz, 1 H), 3.71 (ddd, J = 10.0,
3.6, 2.8 Hz, 1 H), 3.68 (td, J = 6.9, 3.7 Hz, 1 H), 3.56 (d, J =
3.7 Hz, 1 H), 3.52 (dd, J = 10.0, 2.8 Hz, 1 H), 3.39-3.37 (m,
1 H), 3.25 (dd, J = 4.8, 2.8 Hz, 1 H), 2.59-2.53 (m, 1 H), 2.41-
2.39 (m, 2 H), 2.26 (dd, J = 12.8, 7.4 Hz, 1 H), 2.22 (dd, J = 13.8,
6.5 Hz, 1 H), 1.96 (ddd, J = 14.4, 10.6, 1.8 Hz, 1 H), 1.68 (s, 3 H),
1.63 (dt, J = 13.8, 6.4 Hz, 1 H), 1.54-1.49 (m, 3 H), 1.46-1.41
(m, 2 H), 1.35-1.30 (m, 10 H), 0.96 (d, J = 6.4 Hz, 3 H), 0.90 (t,
J = 6.9 Hz, 3 H); 13C NMR (150 MHz, CD3OD) δ 180.2, 134.8,
131.5, 76.3, 75.9, 74.2, 73.8, 72.3, 71.9, 71.6, 71.6, 70.1, 42.3,
42.0, 41.7, 37.1, 34.0, 33.1, 30.8, 30.5, 30.1, 27.1, 23.7, 21.4, 16.8,
14.4; HRMS (ESI) calcd for C27H50O11Na (M þ Na)þ 573.3251,
found 573.3237.
To a solution of the alcohol obtained above (13.6 mg,
14.6 μmol) in CH2Cl2 (0.25 mL) and DMSO (0.25 mL) were
added Et3N (21 μL, 0.154 mmol) and SO3 pry (12.2 mg,
3
77 μmol) at room temperature. After the mixture was stirred
at the same temperature for 30 min, the mixture was poured into
Et2O, washed with H2O and brine, and dried over MgSO4.
Concentration gave the corresponding aldehyde (15.8 mg) as a
pale yellow oil, which was used for the next reaction without
further purification.
To a solution of aldehyde obtained above in t-BuOH
(0.40 mL) and H2O (0.10 mL) were added 2-methyl-2-butene
(32 μL, 0.308 mmol), NaH2PO4 (11.1 mg, 92.4 μmol), and
NaClO2 (10.4 mg, 92.4 μmol) at room temperature. After the
mixture was stirred at the same temperature for 30 min, the
mixture was diluted with H2O and extracted with EtOAc. The
organic layer was washed with brine and dried over MgSO4.
Concentration and column chromatography (CHCl3/MeOH,
49:1) gave carboxylic acid 35 (12.8 mg, 93% in two steps):
Acknowledgment. We thank Okayama Foundation for
Science and Technology, NOVARTIS Foundation (Japan)
for the Promotion of Science, The Mitsubishi Foundation,
J. Org. Chem. Vol. 74, No. 17, 2009 6665