H. Makabe et al. / Bioorg. Med. Chem. 14 (2006) 3119–3130
3127
(0.38 mL, 2.5 M solution in hexane, 0.94 mmol) at
ꢀ10 ꢁC. To this solution was added 29 (175 mg,
0.85 mmol) in THF (0.5 mL). After being stirred for 20
mim, 29 (422 mg, 0.85 mmol) in HMPA (0.45 mL) was
added to the mixture at 0 ꢁC. After stirring for 1 h at this
temperature, the reaction was quenched with saturated
aqueous NH4Cl (10 mL) and the mixture was extracted
with ether (2· 20 mL) and the extract was washed with
water and brine. Drying over MgSO4 and the evapora-
tion of the solvent gave an oil, which was chromato-
graphed over silica gel (hexane/EtOAc = 5:1) to give 30
an oil, which was chromatographed over silica gel (hex-
ane/AcOEt = 4:1) to give 31 (87 mg, 86%) as a color-
less oil. IR (film) mmax cmꢀ1: 3460, 2930, 2856, 1755,
1462, 1360, 1319, 1254, 1189, 1081, 1028, 957, 836,
1
775. H NMR (500 MHz, CDCl3) d: ꢀ0.01–0.07 (6H,
m), 0.88 (9H, s), 1.36–1.38 (6H, m), 1.41 (3H, d,
J = 6.8 Hz), 1.76 (2H, m), 2.07 (2H, m), 2.15 (2H,
m), 2.29 (1H, m), 2.42 (2H, m), 2.50–2.67 (4H, m),
3.78 (1H, m), 3.95 (1H, m), 4.44 (1H, m), 5.01 (1H,
m), 5.43 (0.89H, d, J = 15.7 Hz), 5.81 (0.22H, m),
6.03 (0.89H, dt, J = 15.7, 7.0 Hz), 7.12 (1H, s). FAB-
HRMS calcd for C28H45O6Si [(M+H)+], 505.2985,
found, 505.2990.
(80 mg, 16%) as a colorless oil. IR (film) mmax cmꢀ1
:
2928, 2856, 1765, 1605, 1472, 1254, 1184, 1081, 1005,
1
835, 775. H NMR (500 MHz, CDCl3) d: 0.03 (0.75H,
s), 0.04 (0.75H,s), 0.05 (2.25H, s), 0.12 (2.25H, s), 0.87
(2.25H, s), 0.90 (6.75H, s), 1.24 (2.25H, d, J = 6.2 Hz),
1.38 (0.75H, d, J = 6.2 Hz), 1.31–1.44 (4H, m), 1.73–
1.76 (2H, m), 1.96–2.07 (4H, m), 3.00 (0.25H, m), 3.02
(0.75H, dd, J = 13.9, 7.6 Hz), 4.24 (2H, m), 4.51
(0.75H, m), 4.60 (0.25H, m), 5.98 (0.75H, d,
J = 14.4 Hz), 6.18 (0.5H, m), 6.47 (0.75H, dt, J = 14.4,
7.0 Hz), 7.33–7.42 (3H, m), 7.54–7.57 (2H, m). FAB-
HRMS calcd for C25H39IO3SSiI [(M+H)+],575.1514,
found, 575.1506.
4.1.21. (500S,20R,5S,70EZ,130S)-3-[20-(tert-Butyldimethyl-
silyl)oxy-130-hydroxy-130-(tetrahydrofuran-200-on-500-yl)tri-
dec-70-ene-90-ynyl]-5-methyl-2, 5-dihydrofuran-2-one (31b).
This compound was prepared as just described above in
20
67% yield. ½aꢁ +7.27 (c 1.43, CHCl3). The IR, 1H NMR,
D
13C NMR, and MS spectra were identical with those of
synthetic 31a.
4.1.22.
lyl)oxy-130-hydroxy-130-(tetrahydrofuran-200-on-500-yl)trideca-
nyl]-5-methyl-2, 5-dihydrofuran-2-one (32a). To
(500R,20R,5S,130R)-3-[20-(tert-Butyldimethylsi-
a
4.1.19. (2R,5S,70EZ)-3-[20-(tert-Butyldimethylsilyl)oxy-
80-iodo-70-octenyl]-5-methyl-2,3-dihydrofuran-2-one (10).
To a solution of 30 (37 mg, 0.064 mmol) in CH2Cl2
(1 mL) was added mCPBA (80%, 21 mg, 0.064 mmol)
at 0 ꢁC. After the mixture had been stirred at this tem-
perature for 10 min, Na2S2O3/NaHCO3 (1:1, 2 mL)
was added. After stirring for 1 h, the mixture was
extracted with ether (2· 10 mL) and the extract was
washed with brine. Drying over MgSO4 and the evapo-
ration of the solvent gave an oil, which was dissolved in
toluene (2 mL) and the solution was refluxed for 1 h.
After completion of the reaction, concentration of the
mixture afforded an oil, which was chromatographed
over silica gel (hexane/EtOAc = 10:1) to give 10
refluxing solution of 31 (15 mg, 0.20 mmol) and p-tolu-
enesulfonylhydrazide (2.62 g, 13.4 mmol) in diethoxye-
thane (15 mL) was added sodium acetate (1.36 g,
16.6 mmol) in water (20 mL) over a 4 h period at
120 ꢁC. After being cooled to room temperature, the
reaction mixture was quenched with water and extracted
with AcOEt. The organic layer was washed with brine,
dried over MgSO4, filtered, and concentrated. The resi-
due was chromatographed over silica gel (hexane/
AcOEt = 4:1) to give 32 (13 mg, 89%) as a colorless
:
19
D
oil. ½aꢁ ꢀ3.6 (c 0.10, CHCl3). IR (film) mmax cmꢀ1
3481, 2928, 2855, 1757, 1463, 1343, 1320, 1254, 1188,
1167, 1079, 1028, 837, 775. 1H NMR (500 MHz, CDCl3)
d: ꢀ0.01–0.07 (6H, m), 0.87 (9H, s), 1.24–1.54 (18H, m),
1.41 (3H, d, J = 6.8 Hz), 1.87 (1H, m), 2.10–2.17 (2H,
m), 2.23–2.26 (2H, m), 2.42–2.45 (2H, m), 2.53–2.60
(2H, m), 3.57 (1H, m), 3.95 (1H, m), 4.42 (1H, m),
5.00 (1H, m), 7.12 (1H, m). 13C NMR (125 MHz,
CDCl3) d: ꢀ4.42, 18.07, 18.99, 24.12, 25.08, 25.15,
25.45, 25.87, 25.91, 25.94, 25.98, 28.70, 29.48, 29.54,
29.68, 29.78, 32.76, 32.85, 33.01, 36.99, 70.27, 73.67,
77.47, 82.91, 125.92, 130.91, 151.48, 174.03, 177.07.
FABHRMS calcd for C28H51O6Si [(M+H)+], 511.3455,
found. 511.3462.
(20 mg, 67 %) as a colorless oil. IR (film) mmax cmꢀ1
:
3051, 2930, 2856, 2171, 1756, 1653, 1605, 1471, 1462,
1374, 1361, 1318, 1255, 1203, 1079, 1094, 1028, 949,
1
836, 775. H NMR (500 MHz, CDCl3) d: 0.03 (3H, s),
0.05 (3H, s), 0.87 (9H, s), 1.30–1.44 (6H, m), 1.44 (3H,
d, J = 6.5 Hz), 2.04–2.05 (2H, m), 2.42 (2H, m), 3.96
(1H, m), 5.00 (1H, m), 5.98 (0.75H, d, J = 14.3 Hz),
6.15 (0.5H, m), 6.48 (0.75H, dt, J = 14.3, 6.5 Hz), 7.11
(1H, s). FABHRMS calcd for C19H34O3SiI [(M+H)+],
465.1324, found, 465.1316.
4.1.20.
(500R,20R,5S,70EZ,130R)-3-[20-(tert-Butyldi-
4.1.23. (500S,20R,5S,130S)-3-[20-(tert-Butyldimethylsilyl)oxy-
methylsilyl)oxy-130-hydroxy-130-(tetrahydrofuran-200-on-
500-yl)tridec-70-ene-90-ynyl]-5-methyl-2, 5-dihydrofuran-2-
one (31a). To a solution of the vinyl iodide 10 (60 mg,
0.14 mmol) in Et3N (0.5 mL) was added Cl2Pd(PPh3)2
(2.8 mg, 0.007 mmol) and the resulting solution was
stirred for 1 h. The acetylenic ether 9a (60 mg,
0.14 mmol) along with CuI (1.4 mg, 0.014 mmol) was
then added to the mixture. After being stirred for a fur-
ther 8 h, the reaction was quenched with saturated aque-
ous NH4Cl. The organic materials were extracted with
ether and the extract was washed with brine. Drying
over MgSO4 and the evaporation of the solvent gave
130-hydroxy-130-(tetrahydrofuran-200-on-500-yl)tridecanyl]-
5-methyl-2, 5-dihydrofuran-2-one (32b). This compound
22
D
was obtained as just described above in 76% yield. ½aꢁ
1
+12.4 (c 0.15, CHCl3). The IR, H NMR, 13C NMR,
and MS spectra were identical with those of 31a.
4.1.24. (15R,16R,4R,21S)-Rollicosin (1). To a solution of
32a (13.7 mg, 0.027 mmol) in CH3CN (1 mL) were add-
ed two drops of 46% HF at 0 ꢁC. After being stirred for
1 h, the reaction was quenched with saturated aqueous
NaHCO3. The organic materials were extracted with
ether and the extract was washed with brine. Drying