Total Synthesis of (-)-Mniopetal E
J . Org. Chem., Vol. 65, No. 25, 2000 8605
column chromatography on silica gel (EtOAc/toluene, 1:2) to
provide 1.37 g (94%) of 49, and 46.3 mg (3%) of 48 was
recovered.
56.16, 56.22, 67.8, 77.1, 83.6, 96.8 × 2, 125.3, 130.8 × 2, 144.6,
210.0; HRMS calcd for C19H32O6S2 (M+) 420.1640, found
420.1643.
(2R,3S,4S,7E,9E)-3,4-Bis(m et h oxym et h oxy)-1-ter t-b u -
tyld im eth ylsilyloxy-6,6-d im eth yl-10-(1,3-d ith iola n -2-yl)-
7,9-d eca d ien -2-ol (50). To a cold (0 °C), stirred solution of
49 (370 mg, 0.875 mmol) in CH2Cl2 (8 mL) were added Et3N
(0.35 mL, 2.51 mmol), TBSCl (162 mg, 1.07 mmol), and
4-DMAP (11.2 mg, 91.7 µmol). The mixture was stirred for 20
h, and then Et3N (0.12 mL, 0.86 mmol) and TBSCl (63.5 mg,
0.421 mmol) were added at 0 °C. The mixture was stirred for
an additional 6 h and diluted with saturated brine (40 mL).
The resulting mixture was extracted with CH2Cl2. The com-
bined organic layers were dried and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (EtOAc/hexane, 1:12) to provide 429 mg (91%) of 50 as a
colorless oil (E,E-isomer:other isomers ) >15:1, was deter-
mined by 1H NMR analysis); TLC Rf 0.28 (EtOAc/hexane, 1:5);
[R]22D +24.8 (c 1.71, CHCl3); IR 3480, 1650 cm-1; 1H NMR (300
MHz) δ 0.09 (s, 6H), 0.91 (s, 9H), 1.07 (s, 6H), 1.57-1.71 (m,
2H), 1.95-2.30 (br, 1H), 3.18-3.43 (m, 4H), 3.38 (s, 6H), 3.50-
3.58 (m, 1H), 3.65 (dd, J ) 6.0, 9.9 Hz, 1H), 3.75 (br d, J ) 8.1
Hz, 1H), 3.82 (dd, J ) 3.3, 9.9 Hz, 1H), 3.87-3.93 (m, 1H),
4.59, 4.63 (ABq, J ) 6.6 Hz, 1H × 2), 4.63, 4.83 (ABq, J ) 6.6
Hz, 1H × 2), 5.08 (d, J ) 9.3 Hz, 1H), 5.62 (dd, J ) 9.3, 14.7
Hz, 1H), 5.74 (d, J ) 15.4 Hz, 1H), 5.94 (dd, J ) 10.3, 15.4
Hz, 1H), 6.14 (dd, J ) 10.3, 14.7 Hz, 1H); 13C NMR (75 MHz)
δ -5.4 × 2, 18.2, 25.9 × 3, 27.1, 28.0, 35.8, 39.5 × 2, 43.3,
54.4, 55.9, 56.2, 64.1, 70.9, 77.6, 79.8, 96.9, 97.3, 124.6, 130.2,
131.2, 145.6; HRMS calcd for C25H48O6SiS2 (M+) 536.2662,
found 536.2662.
(3S ,4S ,7E ,9E )-3,4-B is (m e t h o x y m e t h o x y )-1-(d ie t h -
ylp h osp h on o)a cet oxy-6,6-d im et h yl-10-(1,3-d it h iola n -2-
yl)-7,9-d eca d ien -2-on e (53). To a cold (0 °C), stirred solution
of 52 (191 mg, 0.45 mmol) in CH2Cl2 (4 mL) were added
(EtO)2P(O)CH2CO2H (0.15 mL, 0.93 mmol), Et3N (0.16 mL,
1.15 mmol), 4-DMAP (11.0 mg, 90.0 µmol), and 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide hydrochloride (177 mg,
0.97 mmol). The mixture was stirred for 15 h and then diluted
with 0.05 M aqueous HCl (30 mL). The resulting mixture was
extracted with CH2Cl2. The combined organic layers were
washed with 0.05 M aqueous NaOH (30 mL). The organic layer
was separated, and the aqueous layer was extracted with CH2-
Cl2. The combined organic layers were washed with H2O (30
mL). The organic layer was separated, and the aqueous layer
was extracted with CH2Cl2. The organic layers were combined,
dried, and concentrated in vacuo. The residue was purified by
column chromatography on silica gel (acetone/toluene, 1:7) to
provide 232 mg (87%) of 53 as a colorless oil (E,E-isomer:other
1
isomers) >15:1, was determined by H NMR analysis); TLC,
Rf 0.44 (acetone/toluene, 1:1); [R]22 -4.3 (c 1.80, CHCl3); IR
D
1730, 1650 cm-1; H NMR (300 MHz) δ 1.02, 1.05 (2s, 3H ×
1
2), 1.35 (t, J ) 7.2 Hz, 6H), 1.60 (d, J ) 5.4 Hz, 2H), 3.10 (d,
J ) 21.5 Hz, 2H), 3.21-3.39 (m, 4H), 3.37, 3.39 (2s, 3H × 2),
3.85 (dt, J ) 2.2, 5.4 Hz, 1H), 4.20 (quintet, J ) 7.2 Hz, 4H),
4.30 (d, J ) 2.2 Hz, 1H), 4.60, 4.64 (ABq, J ) 6.8 Hz, 1H × 2),
4.68, 4.77 (ABq, J ) 6.5 Hz, 1H × 2), 4.95, 5.08 (ABq, J )
17.6 Hz, 1H × 2), 5.08 (d, J ) 9.3 Hz, 1H), 5.63 (dd, J ) 9.3,
14.7 Hz, 1H), 5.66 (d, J ) 15.2 Hz, 1H), 5.91 (dd, J ) 10.3,
(3S,4S,7E,9E)-3,4-Bis(m eth oxym eth oxy)-1-ter t-bu tyldim -
eth ylsilyloxy-6,6-d im eth yl-10-(1,3-d ith iola n -2-yl)-7,9-d ec-
a d ien -2-on e (51). To a stirred solution of 50 (86.9 mg, 0.16
mmol) in DMSO (4 mL) were added Et3N (0.46 mL, 3.30 mmol)
and SO3‚pyridine (263 mg, 1.65 mmol). The mixture was
stirred for 20 h and diluted with EtOAc (30 mL). The resulting
mixture was washed with H2O (15 mL × 2). The organic layer
was dried and concentrated in vacuo. The residue was purified
by column chromatography on silica gel (EtOAc/hexane, 1:15)
to provide 69.2 mg (79%) of 51 as a colorless oil (E,E-isomer:
other isomers ) >15:1, was determined by 1H NMR analysis);
TLC Rf 0.49 (EtOAc/hexane, 1:3); [R]22D +14.2 (c 1.83, CHCl3);
15.2 Hz, 1H), 6.13 (dd, J ) 10.3, 14.7 Hz, 1H); 13C NMR (75
MHz) δ 16.3 × 2 (d, 3J P,C ) 6.2 Hz), 27.2, 27.7, 33.7 (d, J P,C
)
1
134.3 Hz), 35.5, 39.5 × 2, 43.2, 54.2, 56.1, 56.2, 62.8 × 2 (d,
2J P,C ) 6.2 Hz), 68.6, 76.9, 84.0, 96.76, 96.79, 125.1, 130.6,
2
130.8, 144.7, 165.1 (d, J P,C ) 6.2 Hz), 202.2; HRMS calcd for
C
25H43O10S2P (M+) 598.2036, found 598.2032.
3-[(1S,2S,5E,7E)-1,2-Bis(m eth oxym eth oxy)-4,4-dim eth yl-
8-(1,3-d ith iola n -2-yl)-5,7-octa d ien yl]-2-bu ten -4-olid e (54).
To a cold (0 °C), stirred solution of 53 (172 mg, 0.29 mmol) in
toluene (4 mL) were added 18-crown-6 (161 mg, 0.61 mmol)
and K2CO3 (42.1 mg, 0.305 mmol). The mixture was stirred
for 4.5 h and diluted with saturated brine (25 mL). The
resulting mixture was extracted with CH2Cl2. The combined
organic layers were dried and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(EtOAc/hexane, 1:4) to provide 98.9 mg (77%) of 54 as a
colorless oil (E,E-isomer:other isomers ) >15:1, was deter-
mined by 1H NMR analysis); TLC, Rf 0.58 (EtOAc/hexane, 1:1);
[R]24.5D +6.9 (c 0.97, CHCl3); IR 1780, 1750, 1640 cm-1; 1H NMR
(300 MHz) δ 1.03, 1.08 (2s, 3H × 2), 1.40 (dd, J ) 4.5, 14.9
Hz, 1H), 1.57 (dd, J ) 5.9, 14.9 Hz, 1H), 3.20-3.38 (m, 4H),
3.36, 3.38 (2s, 3H × 2), 3.71-3.79 (m, 1H), 4.59-4.61 (m, 1H),
4.59, 4.69 (ABq, J ) 6.8 Hz, 1H × 2), 4.61, 4.70 (ABq, J ) 6.6
Hz, 1H × 2), 4.81 (dd, J ) 1.7, 18.1 Hz, 1H), 4.98 (dd, J ) 2.0,
18.1 Hz, 1H), 5.08 (d, J ) 9.3 Hz, 1H), 5.58 (d, J ) 15.6 Hz,
1H), 5.67 (dd, J ) 9.3, 14.8 Hz, 1H), 5.95 (dd, J ) 10.3, 15.6
Hz, 1H), 6.00-6.01 (m, 1H), 6.13 (dd, J ) 10.3, 14.8 Hz, 1H);
13C NMR (75 MHz) δ 26.7, 28.2, 35.6, 39.5 × 2, 44.1, 54.1, 55.9,
56.2, 72.2, 76.2, 76.8, 95.3, 96.9, 118.5, 125.8, 130.4, 131.4,
143.9, 166.5, 173.1; HRMS calcd for C21H32O6S2 (M+) 444.1640,
found 444.1641.
1
IR 1730, 1650 cm-1; H NMR (300 MHz) δ 0.09, 0.10 (2s, 3H
× 2), 0.92 (s, 9H), 1.01, 1.05 (2s, 3H × 2), 1.55 (dd, J ) 3.9,
14.9 Hz, 1H), 1.63 (dd, J ) 6.8, 14.9 Hz, 1H), 3.18-3.38 (m,
4H), 3.37 (s, 6H), 3.85-3.92 (m, 1H), 4.40, 4.49 (ABq, J ) 18.7
Hz, 1H × 2), 4.50 (d, J ) 2.0 Hz, 1H), 4.60, 4.67 (ABq, J ) 6.8
Hz, 1H × 2), 4.62, 4.72 (ABq, J ) 6.8 Hz, 1H × 2), 5.07 (d, J
) 9.3 Hz, 1H), 5.63 (dd, J ) 9.3, 14.7 Hz, 1H), 5.64 (d, J )
15.5 Hz, 1H), 5.91 (dd, J ) 10.3, 15.5 Hz, 1H), 6.12 (dd, J )
10.3, 14.7 Hz, 1H); 13C NMR (75 MHz) δ -5.5, -5.4, 18.5, 25.8
× 3, 27.0, 27.9, 35.5, 39.5 × 2, 42.9, 54.2, 56.0, 56.1, 68.9, 76.3,
83.0, 96.5, 96.7, 125.1, 130.5, 130.9, 144.9, 207.8; HRMS calcd
for C24H42O5SiS2 (M+ - CH3OH) 502.2243, found 502.2225.
(3S,4S,7E,9E)-3,4-Bis(m eth oxym eth oxy)-6,6-d im eth yl-
10-(1,3-d ith iola n -2-yl)-1-h yd r oxy-7,9-d eca d ien -2-on e (52).
To a cold (0 °C), stirred solution of 51 (149 mg, 0.28 mmol) in
MeOH (4 mL) was added CSA (6.5 mg, 28 µmol). The mixture
was stirred for 2 h and diluted with saturated NaHCO3 (25
mL). The resulting mixture was extracted with CH2Cl2. The
combined organic layers were dried and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (EtOAc/hexane, 1:3) to provide 98.2 mg (84%) of 52 as a
colorless oil (E,E-isomer:other isomers ) >15:1, was deter-
mined by 1H NMR analysis); TLC Rf 0.47 (EtOAc/hexane, 2:3);
[R]27D +3.9 (c 1.17, CHCl3); IR 3460, 1720, 1650 cm-1; 1H NMR
(300 MHz) δ 1.03, 1.05 (2s, 3H × 2), 1.56 (dd, J ) 4.6, 14.9
Hz, 1H), 1.63 (dd, J ) 6.4, 14.9 Hz, 1H), 3.18-3.42 (m, 4H),
3.36, 3.39 (2s, 3H × 2), 3.84-3.91 (m, 1H), 4.34 (d, J ) 2.4
Hz, 1H), 4.46 (s, 2H), 4.59, 4.64 (ABq, J ) 6.8 Hz, 1H × 2),
4.64, 4.77 (ABq, J ) 6.6 Hz, 1H × 2), 5.08 (d, J ) 9.3 Hz, 1H),
5.64 (dd, J ) 9.3, 14.7 Hz, 1H), 5.65 (d, J ) 15.4 Hz, 1H), 5.92
(dd, J ) 10.3, 15.4 Hz, 1H), 6.13 (dd, J ) 10.3, 14.7 Hz, 1H);
13C NMR (75 MHz) δ 27.2, 27.8, 35.5, 39.5 × 2, 43.6, 54.2,
(1S,2R,3S,6S,9S,10S)- (55),43 (1R,2R,3S,6R,9R,10R)- (56),
a n d (1R,2R,3S,6S,9S,10R)-2,3-Bis(m eth oxym eth oxy)-5,5-
d im eth yl-9-(1,3-d ith iola n -2-yl)-12-oxa tr icyclo[8.3.0.01,6]-
tr id ec-7-en -11-on e (58). Compound 54 (95.2 mg, 0.21 mmol)
was dissolved in degassed toluene (7.1 mL), and a crystal of
BHT was added. The solution was transferred into a 20 mL
sealed tube equipped with a screwed stopper, and the tube
was filled with argon. The tube was heated to 180 °C for 34 h.
After being cooled to ambient temperature, the solution was
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (EtOAc/hexane, 1:6) to provide
58.2 mg (62%) of 55, 20.3 mg (21%) of 56, and 2.1 mg (2%) of
58. Compound 55 was obtained as colorless amorphous solids;