Ohta et al.
JOCArticle
2.66 (dd, 1H, J = 18.1, 9.5 Hz), 2.48 (m, 2H), 2.36 (dd, 1H, J =
18.1, 1.7 Hz), 2.22 (q, 1H, J = 8.5 Hz), 1.90 (ddd, 1H, J =
14.7, 8.2, 3.3 Hz); 13C NMR (50 MHz, CDCl3) δ 176.9, 138.3,
137.7, 135.5, 130.6, 129.2 (2C), 128.6, 126.2, 82.4, 76.3, 74.9, 73.2,
58.5, 56.2, 43.9, 42.5, 39.8, 34.1; IR (KBr) 3406, 3010, 2932, 1762,
1091, 755 cm-1; Mass (ESI, Pos., 20 V) m/z 355 (M þ Na); Anal.
Calcd for C19H24O5: C, 68.66; H, 7.28; Found: C, 68.29; H, 7.60;
HPLC conditions: YMC-Pack-ODS-A-302; MeCN/H2O =
20/80 (0-20 min) f 2%/min (20-35 min) f 50/50 (35-45 min);
detection, 210 nm; flow rate, 1.0 mL/min; retention time of 17
was 17.6 min, and that of 15-β was 15.6 min.
14.0, 5.0 Hz), 1.81 (m, 2H), 1.54 (m, 2H), 0.87 (s, 9H), 0.84 (s,
9H), 0.05 (m, 6H), -0.08 (s, 3H), -0.17 (s, 3H); 13C NMR (50
MHz, CDCl3) δ 138.9, 137.9, 133.8, 131.5, 129.3 (2C), 128.2,
125.7, 79.6, 74.9, 74.9, 74.5, 61.9, 58.3, 56.6, 49.2, 45.5, 42.9,
31.6, 26.0 (3C), 25.9 (3C), 18.3, 18.0, -4.41, -4.44, -4.7, -5.0;
IR (KBr) 3383, 2953, 2929, 2856, 1741, 1472, 1254, 1105, 837,
776 cm-1; Mass (ESI, Pos., 20 V) m/z 587 (M þ Na); HRMS
(ESI) Calcd for C31H56O5Si2þNaþ 587.3559; Found: 583.3586;
Anal. Calcd for C31H56O5Si2: C, 65.91; H, 9.99; Si, 9.94; Found: C,
65.72; H, 10.24; Si, 9.54; HPLC conditions: YMC-Pack-ODS-A-302;
MeCN/H2O = 75/25; detection: 210 nm; flow rate: 1.0 mL/min;
retention time of 19 was 12.6 min, and that of 15-β was 13.3 min.
Methyl 4-({2-[(1R,2R,3R,5S)-3-{[dimethyl(2-methyl-2-propanyl)-
silyl]oxy}-2-{(1E,3S)-3-{[dimethyl(2-methyl-2-propanyl)silyl]oxy}-
4-[3-(methoxymethyl)phenyl]-1-buten-1-yl}-5-hydroxycyclopentyl]-
ethyl}sulfanyl)butanoate 20. To a solution of γ-thiobutyrolactone
(2.73 g, 26.8 mmol) in MeOH (5.5 mL) was added Cs2CO3
(873 mg, 2.68 mmol) under Ar and stirred for 2 h at 50 °C. The
resulting solution was cooled to rt, and then the solution was
diluted with DMA (18.2 mL) to give methyl 4-mercaptobutanoate
DMA solution.
To a solution of MsCl (0.83 mL, 11 mmol) in THF
(30.2 mL) was added a mixed solution of diisopropylethylamine
(2.6 mL, 15 mmol) and 19 (5.04 g, 8.92 mmol) in THF (30.4 mL) at
-20 °C and stirred for 30 min. To a slurry was added MeOH
(0.14 mL, 3.6 mmol) at -20 °C and stirred for 30 min. To a
slurry was added TMSCl (1.7 mL, 13 mmol) at -20 °C and
stirred for 30 min. The slurry was warmed to 0 °C and Cs2CO3
(17.4 g, 53.5 mmol) was added and stirred for 10 min. To the
slurry was added a solution of methyl 4-mercaptobutanoate in
DMA at 0 °C and warmed to 40 °C and stirred for another 2.5 h.
To a slurry was added MeOH (10 mL) at rt and stirred for 16 h.
The reaction mixture was diluted with MTBE/EtOAc = 2/1
(101 mL), then quenched with H2O (50 mL) under 15 °C.
Aqueous layer was separated and extracted with MTBE/
EtOAc = 2/1 (50 mL) and the combined organic layers was
washed with H2O (25 mL), aq. 20% NaCl solution (25 mL)
and dried over anhydrous MgSO4. The solvent was removed by
evaporation and the residue was purified by column chroma-
tography on silica gel (BW-235S, 169 g, Toluene:EtOAc = 10:1)
to give 20 as a colorless oil (4.75 g, 78.2%, 93.2% de, 97.3 area%).
Rf 0.40 (EtOAc/n-hexane, 1/4); [R]20D þ11.9 (c 1.02, EtOH); 1H
NMR (400 MHz, CDCl3) δ7.24 (t, 1H, J = 7.6 Hz), 7.15 (d,
1H, J = 7.7 Hz), 7.13 (s, 1H), 7.07 (d, 1H, J = 7.5 Hz), 5.49
(dd, 1H, J = 15.4, 5.7 Hz), 5.35 (ddd, 1H, J = 15.3, 8.9,
0.92 Hz), 4.42 (s, 2H), 4.22 (q, 1H, J = 6.0), 4.12 (m, 1H),
3.98 (m, 1H), 3.65 (s, 3H), 3.37 (s, 3 H), 2.73 (d, 2H, J = 6.6),
2.54 (m, 4H), 2.42 (t, 2H, J = 7.3), 2.22 (m, 1H), 1.88 (m, 5H),
1.59 (m, 2H), 0.86 (s, 9H), 0.82 (s, 9H), 0.04 (m, 6H), -0.13
(s, 3H), -0.24 (s, 3H); 13C NMR (50 MHz, CDCl3) δ 173.6,
138.9, 138.0, 133.7, 131.2, 129.4, 129.3, 128.2, 125.6, 80.1, 74.8,
74.6, 74.5, 58.2, 56.9, 51.7, 50.6, 45.6, 43.0, 32.9, 31.3, 30.6, 29.0,
26.0 (3C), 25.9 (3C), 24.8, 18.3, 18.0, -4.4, -4.5, -4.7, -5.1; IR
(KBr) 3513, 2928, 2856, 1254, 1104, 971, 837, 776 cm-1; Mass
(ESI, Pos., 20 V) m/z 703 (M þ Na); HRMS (ESI) Calcd for
C36H64O6S1Si2þNaþ: 703.3854; Found: 703.3878; Anal. Calcd for
C36H64O6S1Si2 C, 63.43; H, 9.56; S, 4.71; Si, 8.25; Found: C, 63.48;
H, 9.47; S, 4.71; Si, 8.07; HPLC conditions: YMC-Pack-C4-A-802;
MeCN/H2O = 80/20 (0-15 min) f 2%/min (15-25 min)f 100/
0 (25-35 min); detection: 210 nm; flow rate: 1.0 mL/min; retention
time of 20 was 17.6 min, and that of 15-β was 16.7 min.
(3aR,4R,5R,6aS)-5-{[Dimethyl(2-methyl-2-propanyl)silyl]oxy}-4-
{(1E,3S)-3-{[dimethyl(2-methyl-2-propanyl)silyl]oxy}-4-[3-(methoxy-
methyl)phenyl]-1-buten-1-yl}hexahydro-2H-cyclopenta[b]furan-2-
one 18. To a solution of diol 17 (3.0 g, 8.8 mmol) and imidazole
(15.6 g, 22.9 mmol) in DMA (17.5 mL) was added TBSCl (3.3 g,
22 mmol) portionwise under 0 °C. The solution was warmed to
50 °C and stirred for 3 h then cooled to room temperature. The
solution was diluted with MTBE (12.0 mL) and quenched with
H2O (6.0 mL) under 20 °C. Aqueous layer was separated and
organic layer was washed with H2O (6.0 mL) and aq. 20% NaCl
solution (6.0 mL) and dried over anhydrous MgSO4. The solvent
was removed by evaporation and dried in vacuo to give crude 18
as white powder (5.45 g, 110%). To a solution of crude 18 (1.0 g)
inMeOH(30mL) andH2O (3 mL) was addedthe seed18(1.0 mg)
at 10 °C and stirred for 4.5 h. The resulting slurry was cooled to
5 °C at the speed of 20 °C /h and stirred for 1 h. To the resulting
slurry was slowly added ice-cooled H2O (5 mL) for 10 min and
stirred for another 1 h at 5 °C. The resulting slurry was filtered off
and washed with ice-cooled H2O (10 mL) and dried in vacuo at
40 °C to give 18 as a white powder (819 mg, 91.4% in 2 steps from
diol 17, 97.0 HPLC area %). Rf 0.49 (EtOAc/n-hexane, 1/3); Mp
68-70 °C; [R]20D -20.2(c 1.08, EtOH); 1H NMR (400 MHz, CDCl3)
δ 7.24 (m, 1H), 7.15 (m, 2H), 7.07 (m, 1H), 5.52 (ddd, 1H, J =
15.5, 5.7, 1.0 Hz), 5.33 (ddd, 1H, J = 15.5, 7.7, 1.1 Hz), 4.91
(td, 1H, J = 7.1, 2.2 Hz), 4.42 (s, 2H), 4.23 (m, 1H), 3.93 (q, 1H,
J = 5.2 Hz), 3.38 (s, 3H), 2.73 (m, 3H), 2.56 (m, 1H), 2.43 (m, 2H),
2.17 (ddd, 1H, J = 14.8, 7.0, 5.7 Hz), 1.95 (m, 1H), 0.87 (s, 9H),
0.83 (s, 9H), 0.04 (s, 6H), -0.12 (s, 3H), -0.20 (s, 3H); 13C NMR
(50 MHz, CDCl3) δ 177.1, 138.7, 138.1, 135.0, 129.3, 129.2 (2C),
128.2, 125.7, 83.6, 78.2, 74.8, 74.4, 58.3, 56.8, 45.4, 42.4, 40.7, 35.2,
25.95 (3C), 25.87 (3C), 18.3, 18.1, -4.5, -4.6, -4.7, -5.0; IR (KBr)
2929, 2856, 1752, 1250, 1165, 1117, 836, 777 cm-1; Mass (ESI, Pos.,
20 V) m/z583 (M þ Na); HRMS (ESI) Calcd for C31H52O5Si2þNaþ
583.3246; Found: 583.3265; Anal. Calcd for C31H52O5Si2 C, 66.38;
H, 9.34; Si, 10.01; Found: C, 66.02; H, 9.38; Si, 9.93; HPLC:
YMC-Pack-ODS-A-302; MeCN/H2O = 40/60 (0-5 min) f 2%/
min (5-30 min) f 90/10 (30-45 min); detection: 210 nm; flow rate:
1.0 mL/min; retention time of 18 was 34.5 min.
(1S,2R,3R,4R)-4-{[Dimethyl(2-methyl-2-propanyl)silyl]oxy}-
3-{(1E,3S)-3-{[dimethyl(2-methyl-2-propanyl)silyl]oxy}-4-[3-
(methoxymethyl)phenyl]-1-buten-1-yl}-2-(2-hydroxyethyl)cyclo-
pentanol 19. To a slurry LiBH4 (102 mg, 4.70 mmol) in THF
(8.3 mL) was added solution of 18 (2.78 g, 4.95 mmol) in THF
(8.3 mL) at 0 °C and then stirred at 35 °C for 3 h. The reaction
mixture was diluted with EtOAc (14 mL) and quenched with aq.
20 wt% NH4Cl solution (8.3 mL) at 0 °C. Aqueous layer
was separated and organic layer was washed with aq. 20%
NaCl solution (5.6 mL) and dried over anhydrous MgSO4. The
solvent was removed by evaporation and dried in vacuo to give
19 as white pale yellow oil (2.84 g, 102%. 90.8% de, 98.7 area%)
without further purification. Rf 0.34 (EtOAc/n-hexane, 1/1);
Methyl 4-({2-[(1R,2R,3R)-3-{[dimethyl(2-methyl-2-propanyl)silyl]-
oxy}-2-{(1E,3S)-3-{[dimethyl(2-methyl-2-propanyl)silyl]oxy}-4-[3-
(methoxymethyl)phenyl]-1-buten-1-yl}-5-oxocyclopentyl]ethyl}sulfanyl)-
butanoate 21. To a stirred solution of 20 (2.0 g, 2.9 mmol) and
diisopropylethylamine (2.23 g, 17.3 mmol) in EtOAc (20 mL) was
[R]20 -5.4 (c 1.00, EtOH); 1H NMR (400 MHz, CDCl3)
D
δ7.24 (m, 1H), 7.15 (m, 2H), 7.08 (m, 1H), 5.47 (dd, 1H, J =
15.2, 6.2 Hz), 5.30 (ddd, 1H, J = 15.3, 9.0, 0.82 Hz),4.42
(s, 2H), 4.25 (m, 1H), 4.17 (m, 1H), 3.96 (m, 1H), 3.66 (m, 1H),
3.57 (m, 1H), 3.39 (s, 3 H), 2.80 (dd, 1H, J = 13.4, 7.1 ), 2.72
(dd, 1H, J = 13.3, 6.1 Hz), 2.24 (m, 1H), 1.91 (dt, 1H, J =
added a solution of SO3 Py (1.38 g, 8.64 mmol) in DMSO
(10 mL) slowly at a temperature below 10 °C under Ar. After
3
8306 J. Org. Chem. Vol. 74, No. 21, 2009