Total Synthesis of EI-1941-1, -2, -3
ature, and the reaction mixture was stirred for 1 h. The
reaction mixture was concentrated under reduced pressure.
The residue was purified by silica gel column chromatography
(AcOEt/hexane ) 1:1-1:3) to afford carboxylic acid 23t (23 mg,
98%) as a colorless oil: 1H NMR (400 MHz, CD3OD) δ 0.14
(3H, s), 0.21 (3H, s), 0.90 (9H, s), 0.92 (3H, t, J ) 7.3 Hz), 1.44
(2H, sextet, J ) 7.3 Hz), 1.99-2.21 (2H, m), 3.53 (1H, d, J )
3.9 Hz), 3.72 (1H, dd, J ) 3.9 Hz), 5.21 (1H, br-s), 6.32 (1H,
td, J ) 6.8 Hz, 16.0 Hz), 6.46 (1H, d, J ) 16.0 Hz); 13C NMR
(100 MHz, CD3OD) δ -4.7, -4.7, 13.7, 17.9, 21.8, 25.5, 36.1,
53.6, 55.7, 65.6, 122.1, 134.5, 137.9, 143.4, 172.6, 196.3; FT-
IR (neat) ν 3375, 2929, 2858, 1693, 1680, 1464, 1338, 1099,
781, 741 cm-1; HRMS (FAB) [M + Na]+ calcd for [C18H28O5Si
+ Na]+ 375.1604, found 375.1577; [R]22D -61.4 (c 0.11, MeOH).
NMR (125 MHz, CDCl3) δ 13.5, 17.9, 25.7, 29.6, 50.0, 51.3,
62.7, 67.3, 104.7, 117.2, 149.8, 162.5, 166.9; FT-IR (neat) ν
3419, 2927, 2856, 1726, 1651, 1585, 1464, 1254, 1080, 974, 839,
781 cm-1; HRMS (FAB) [M]+ calcd for C18H28O5Si 352.1706,
found 352.1680; [R]23 +104.1 (c 0.08, MeOH). 30: 1H NMR
D
(400 MHz, CDCl3) δ 0.12 (3H, s), 0.22 (3H, s), 0.85 (9H, s),
0.95 (3H, t, J ) 7.4 Hz), 1.67 (2H, sextet, J ) 7.4 Hz), 2.44
(2H, t, J ) 7.4 Hz), 3.47 (1H, dd, J ) 2.5, 4.3 Hz), 3.59 (1H,
dd, J ) 2.2, 4.3 Hz), 4.79 (1H, d, J ) 8.8 Hz), 5.12 (1H, d, J )
2.2 Hz), 6.29 (1H, s); 13C NMR (100 MHz, CDCl3) δ -5.0, -4.6,
13.5, 18.1, 20.2, 25.8, 29.7, 35.8, 53.1, 54.4, 62.4, 66.1, 101.4,
117.2, 149.4, 162.3, 165.4; FT-IR (neat) ν 3410, 2929, 2856,
1722, 1645, 1574, 1464, 1252, 1117, 1065, 920, 839, 777 cm-1
;
HRMS (FAB) [M]+ calcd for C18H28O5Si 352.1706, found
352.1689; [R]23 +81.3 (c 0.21, MeOH).
D
(2S,3S,7R,8S,11R)-3-(tert-Butyldimethylsiloxy)-8-chlo-
rmercurio-7-propyl-1,6-dioxatricyclo[8.1.0.04,9]undec-4-
en-5,10-dione (26). To a solution of carboxylic acid 23t (21.0
mg, 0.06 mmol) in EtCN (2.1 mL) were added MS4A (6.3 mg,
30 wt %) and Hg(OTf)2/MeCN (0.25 mL, 0.071 mmol) at -78
°C, and the reaction mixture was stirred for 3 min. The
reaction mixture was quenched with saturated aqueous NaH-
CO3 and saturated aqueous NaCl (1:1). The organic materials
were extracted with AcOEt, washed with saturated aqueous
NaCl, dried over anhydrous Na2SO4, and then concentrated
under reduced pressure. The residue was purified by silica gel
column chromatography (AcOEt/hexane ) 1:3) to afford 26
(35.0 mg, 99%) as a colorless solid: 1H NMR (400 MHz, CDCl3)
δ 0.12 (3H, s), 0.24 (3H, s), 0.87 (9H, s), 0.96 (3H, t, J ) 7.3
Hz), 1.49-1.70 (2H, m), 1.77-1.93 (2H, m), 2.82 (1H, br-d, J
) 11.6 Hz), 3.70 (1H, br-d, J ) 3.8 Hz), 3.75 (1H, dd, J ) 1.9,
3.8 Hz), 4.55 (1H, ddd, J ) 3.5, 7.9, 11.6 Hz), 5.43 (1H, br-s);
13C NMR (150 MHz, CDCl3) δ -4.9, -4.5, 13.7, 18.2, 25.6, 29.7,
38.8, 42.4, 53.1, 55.4, 61.9, 80.6, 136.5, 142.2, 164.2, 196.9; FT-
IR (neat) ν 2958, 2929, 2858, 2360, 1714, 1680, 1252, 1090,
839, 781 cm-1; HRMS (FAB) [M + H]+ calcd for C18H28ClHgO5-
(2S,3S,7S,10R,11S)-3-(tert-Butyldimethylsiloxy)-10-hy-
droxy-7-propyl-1,6-dioxatricyclo[8.1.0.04,9]undec-4-en-5-
one (31) and (2S,3S,7R,10R,11S)-3-(tert-Butyldimethyl-
siloxy)-10-hydroxy-7-propyl-1,6-dioxatricyclo[8.1.0.04,9]-
undec-4-en-5-one (32). To a solution of 29 (10.0 mg, 0.0284
mmol) in AcOEt (2.8 mL) was added 10% Pd/C (3.0 mg, 0.0028
mmol) at room temperature, and the reaction mixture was
stirred for 3 h under an H2 atmosphere. The reaction mixture
was filtered through a pad of Celite, and concentrated under
reduced pressure. The residue was purified by preparative
thin-layer chromatography (AcOEt/hexane ) 1:3) to afford an
inseparable mixture of 31 and 32 (9.5 mg, 95%, 95:5 diaste-
reoselectivity) as a colorless oil. 31: 1H NMR (400 MHz, CDCl3)
δ 0.12 (3H, s), 0.22 (3H, s), 0.85 (9H, s), 0.91 (3H, t, J ) 7.3
Hz), 1.37-1.58 (2H, m), 1.74-1.79 (1H, m), 2.29-2.34 (1H,
m), 2.38 (1H, dd, J ) 4.9, 18.0 Hz), 2.62 (1H, dd, J ) 8.4, 18.0
Hz), 3.34-3.36 (1H, m), 3.43-3.45 (1H, m), 4.32 (1H, br-d, J
) 8.7 Hz), 4.45-4.51 (1H, m), 5.03 (1H, d, J ) 2.4 Hz); 13C
NMR (100 MHz, CDCl3) δ -5.0, -4.7, 13.7, 17.9, 18.2, 25.7,
32.0, 36.4, 50.3, 51.8, 62.2, 67.5, 124.3, 148.6, 163.9; FT-IR
(neat) ν 3423, 2958, 2931, 2858, 1716, 1254, 1084, 868, 839,
779 cm-1; HRMS (FAB) [M + H]+ calcd for C18H31O5Si
355.1941, found 355.1948.
Si 589.1101, found 589.1074; [R]23 +48.8 (c 0.087, MeOH).
D
(2R,3S,11S)-3-(tert-Butyldimethylsiloxy)-7-propyl-1,6-
dioxatricyclo[8.1.0.04,9]undec-4,7-dien-5,10-dione (28). To
a solution of carboxylic acid 23t (100.0 mg, 0.567 mmol) in
THF (5.7 mL) was added p-benzoquinone (26.2 mg, 2.84 mmol)
and Pd(PhCN)2Cl2 (12.4 mg, 0.0567 mmol) at room tempera-
ture, and the reaction mixture was stirred for 20 h. The
reaction mixture was filtered through a pad of Celite, and
concentrated under reduced pressure. The residue was purified
by silica gel column chromatography (AcOEt/hexane ) 1:3-
1:5) to afford 28 (70.0 mg, 70%) as a yellow oil: 1H NMR (400
MHz, CDCl3) δ 0.15 (3H, s), 0.26 (3H, s), 0.85 (9H, s), 0.96
(3H, t, J ) 7.5 Hz), 1.68 (2H, sextet, J ) 7.5 Hz), 2.47 (2H, t,
J ) 7.5 Hz), 3.63 (1H, br-d, J ) 3.9 Hz), 3.77 (1H, dd, J ) 2.0,
3.9 Hz), 5.29 (1H, br-s), 6.28 (1H, br-s); 13C NMR (100 MHz,
CDCl3) δ -4.9, -4.6, 13.5, 20.1, 25.7, 35.8, 52.6, 56.7, 61.9,
98.1, 125.4, 139.6, 139.6, 162.3, 166.9, 192.9; FT-IR (neat) ν
2956, 2929, 2856, 1732, 1705, 1641, 1577, 1464, 1257, 1086,
839, 781 cm-1; HRMS (FAB) [M]+ calcd for C18H26O5Si
(2S,3S,7S,11R)-3-(tert-Butyldimethylsiloxy)-7-propyl-
1,6-dioxatricyclo[8.1.0.04,9]undec-4-en-5,10-dione (33). To
a solution of 31 and 32 (10.0 mg, 0.0283 mmol) in CH2Cl2 (1.0
mL) was added MnO2 (61.3 mg, 0.705 mmol) at 0 °C under an
argon atmosphere, and the reaction mixture was stirred for 1
h at that temperature. The reaction mixture was filtered
through a pad of Celite, and concentrated in vacuo. The residue
was purified by preparative thin-layer chromatography (AcOEt/
hexane ) 1:5) to afford 33 (9.2 mg, 92%; 95:5 diastereoselec-
tivity) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 0.14
(3H, s), 0.45 (3H, s), 0.85 (9H, s), 1.33-1.58 (3H, m), 1.81-
1.72 (1H, m), 2.52 (1H, dd, J ) 4.6, 18.1 Hz), 2.63 (1H, dd, J
) 7.9, 18.1 Hz), 3.56 (1H, br-d, J ) 3.9 Hz), 3.71 (1H, dd, J )
1.9, 3.9 Hz), 4.48-4.54 (1H,m), 5.16 (1H, br-s); 13C NMR (100
MHz, CDCl3) δ -4.8, -4.75, 13.7, 18.1, 18.2, 25.7, 29.7, 36.2,
52.3, 56.4, 61.9, 135.8, 139.5, 163.5, 194.4; FT-IR (neat) ν 2927,
350.1550, found 350.1579; [R]23 -14.1 (c 0.17, MeOH).
2854, 1726, 1695, 1464, 1252, 1240, 1101, 1084, 839, 781 cm-1
;
D
HRMS (FAB) [M + H]+ calcd for C18H29O5Si 353.1784, found
(2S,3S,10R,11S)-3-(tert-Butyldimethylsiloxy)-10-hy-
droxy-7-propyl-1,6-dioxatricyclo[8.1.0.04,9]undec-4,7-dien-
5-one (29) and (2S,3S,10S,11S)-3-(tert-Butyldimethylsil-
oxy)-10-hydroxy-7-propyl-1,6-dioxatricyclo[8.1.0.04,9]un-
dec-4,7-dien-5-one (30). To a solution of 28 (43.0 mg, 0.123
mmol) in MeOH (1.3 mL) was added NaBH4 (14.0 mg, 0.368
mmol) at 0 °C, and the reaction mixture was stirred for 20
min at that temperature. The reaction mixture was quenched
with saturated aqueous NH4Cl. The organic materials were
extracted with AcOEt, washed with saturated aqueous NaCl,
dried over anhydrous Na2SO4, and then concentrated under
reduced pressure. The residue was purified by silica gel column
chromatography (CHCl3) to afford 29 and 30 (42.0 mg, 98%,
50:50 diastereoselectivity) as a colorless oil. 29: 1H NMR (400
MHz, CDCl3) δ 0.13 (3H, s), 0.25 (3H, s), 0.86 (9H, s), 0.96
(3H, t, J ) 7.5 Hz), 3.43 (1H, m), 3.52 (1H, m), 4.55 (1H, br-d,
J ) 10.2 Hz), 5.23 (1H, d, J ) 2.8 Hz), 5.94 (1H, br-s); 13C
353.1782; [R]22 -10.5 (c 0.12, MeOH).
D
(2R,3S,7S,11R)-3-Hydroxy-7-propyl-1,6-dioxatricyclo-
[8.1.0.04,9]undec-4-en-5,10-dione (EI-1941-2 (2)). To a solu-
tion of 33 (16.6 mg, 0.0471 mmol) in CH3CN (1.9 mL) was
added HF‚Pyr (0.5 mL) at 0 °C, and the reaction mixture was
stirred for 4 h at that temperature. The reaction mixture was
quenched with saturated aqueous NaHCO3. The organic
materials were extracted with AcOEt, washed with saturated
aqueous NaCl, dried over anhydrous Na2SO4, and then con-
centrated under reduced pressure. The residue was purified
by preparative thin-layer chromatography (AcOEt/hexane )
1:1) to afford EI-1941-2 (2) (11.2 mg, quant.) as a colorless
powder: 1H NMR (400 MHz, CD3CN) δ 0.93 (3H, t, J ) 7.3
Hz), 1.35-1.51 (2H, m), 1.57-1.66 (1H, m), 1.69-1.78 (1H,
m), 2.46 (1H, ddd, J ) 1.0 9.7, 18.1 Hz), 2.54 (1H, ddd, J )
1.3, 4.6, 18.1 Hz), 3.56 (1H, dd, J ) 1.0, 3.7 Hz), 3.85 (1H, dd,
J. Org. Chem, Vol. 70, No. 24, 2005 9913