J.-Z. Wu et al. / Tetrahedron 65 (2009) 289–299
297
(400 MHz, CDCl3):
d
7.30–7.26 (m, 5H), 5.59 (dt, J¼10.8, 7.6 Hz, 1H),
The combined organic layers were washed in turn with aq satd
CuSO4, aq satd NaHCO3, water, and brine before being dried over
anhydrous Na2SO4. After removal of the solvent by rotary evapo-
ration, the crude residue was chromatographed on silica gel (9:2
PE/EtOAc) to afford natural verbalactone 13 as a colorless oil (15 mg,
5.33 (dd, J¼10.8, 9.2 Hz, 1H), 4.95–4.92 (m, 1H), 4.52 (t, J¼6.0 Hz,
1H), 4.54 (d, J¼12 Hz, 1H), 4.34–4.27 (m, 1H), 4.30 (d, J¼12 Hz, 1H),
4.16–4.13 (m, 1H), 2.58–2.38 (m, 4H), 2.06–1.76 (m, 5H), 1.68–1.61
(m, 1H), 1.52–1.49 (m, 2H), 1.39–1.35 (m, 2H), 1.28–1.26 (m, 6H),
0.91 (t, J¼7.6 Hz, 6H), 0.85 (s, 9H), 0.82 (s, 9H), 0.06 (m, 12H). 13C
NMR (100 MHz, CDCl3): 171.2, 138.8, 133.4, 130.6, 128.2 (2C’s), 127.7
(2C’s), 127.3, 71.0, 70.8, 69.7, 66.6, 66.4, 43.0, 42.0, 41.6, 41.5, 34.5,
31.7, 29.9, 25.8 (6C’s), 24.8, 22.9, 22.5, 18.0, 17.9, 14.0, 13.8, ꢂ4.56
(2C’s), ꢂ4.6, ꢂ4.6, ꢂ4.9; FTIR (film): 2956, 1735, 1713, 1463, 1256,
1086 cmꢂ1; ESIMS: m/z 729.4 ([MþNa]þ). ESIHRMS calcd for
C39H70Si2O7Na ([MþNa]þ): 729.4552; found: 729.4563.
27
25
0.040 mmol, 88%). [
a
]
þ8.7 (c 1.0, CHCl3) (lit.12a
[
a
]
þ7.3 (c 0.9,
D
25
20
CHCl3); lit.12b
[
a
]
D
þ6.2 (c 0.9, CHCl3); lit.12e
[a]
D
D þ8.5 (c 0.5,
CHCl3)). 1H NMR (400 MHz, CDCl3):
d 4.95–4.98 (m, 2H), 4.06–4.08
(m, 2H), 3.73 (br s, 2H, 2OH’s), 2.67 (d, J¼4.5 Hz, 4H), 2.08 (ddd,
J¼3.2, 10.2, 15.3 Hz, 2H), 1.97 (dt, J¼15.3, 4.3 Hz, 2H), 1.48–1.61 (m,
4H), 1.50–1.59 (m, 12H), 0.89 (t, J¼7.0 Hz, 6H). 13C NMR (100 MHz,
CDCl3): 172.9, 72.5, 64.5, 39.4, 38.2, 35.4, 31.7, 25.5, 22.5, 13.9; FTIR
(film): 3448, 2956, 1736, 1466, 1281, 1117 cmꢂ1; ESIMS: m/z 395.0
([MþNa]þ). ESIHRMS calcd for C20H36O6Na ([MþNa]þ): 395.2404;
found: 395.2398.
4.22. Conversion of 29 to 30
A mixture of 29 (27 mg, 0.038 mmol) and 10% Pd–C (250 mg) in
EtOAc (0.4 mL) was stirred at ambient temperature under H2
(1 atm) until TLC showed completion of the reaction. The solids
were filtered off (washing with EtOAc). The combined filtrate/
4.25. Conversion of 28 to 32
A mixture of 28 (61 mg, 0.0083 mmol) and 10% Pd–C (84 mg)
in EtOAc (0.6 mL) was stirred at ambient temperature under H2
(1 atm) until TLC showed completion of the reaction. The solids
were filtered off (washing with EtOAc). The combined filtrate/
washings were evaporated under reduced pressure to afford 30 as
27
a colorless oil (22 mg, 0.036 mmol, 95%). [
a
]
þ1.89 (c 1.6, CHCl3).
D
1H NMR (400 MHz, CDCl3):
d
4.97–4.95 (m, 1H), 4.32–4.31 (m, 1H),
4.17–4.14 (m, 1H), 3.75–3.73 (m, 1H), 2.50–2.46 (m, 4H), 1.90–1.80
(m, 1H), 1.79–1.71 (m, 2H), 1.56–1.40 (m, 3H), 1.36–1.23 (m, 12H),
1.04–0.85 (m, 24H), 0.14–0.07 (m, 12H). 13C NMR (100 MHz,
CDCl3): 175.9, 170.8, 71.4, 70.3, 69.1, 66.4, 43.9, 43.3, 41.6, 41.5, 37.6,
34.5, 31.9, 31.6, 25.7 (3C’s), 25.67 (3C’s), 25.1, 24.8, 22.6, 22.5, 17.9,
17.8, 14.0, 13.9, ꢂ4.4, ꢂ4.6, ꢂ4.8, ꢂ4.9; FTIR (film): 3437, 2956,
washings were evaporated under reduced pressure to afford 32 as
27
a colorless oil (47 mg, 0.072 mmol, 87%). [
a
]
þ0.16 (c 1.15,
D
CHCl3). 1H NMR (300 MHz, CDCl3):
d
5.00–4.96 (m, 1H), 4.55–4.51
(dd, J¼6.7, 4.5 Hz, 1H), 4.34–4.29 (m, 1H), 3.85–3.80 (m, 1H), 3.73
(m, 1H), 3.29 (s, 3H), 3.28 (s, 3H), 3.0 (s, 1H), 2.58–2.46 (m, 2H),
1.84–1.47 (m, 8H), 1.42–1.35 (m, 2H), 1.29–1.26 (m, 12H), 0.89 (s,
24H), 0.13 (d, J¼4.3 Hz, 6H), 0.06 (d, J¼2.4 Hz, 6H). 13C NMR
(100 MHz, CDCl3): 170.7, 101.6, 71.7, 69.3, 66.1, 52.6, 52.3, 44.0,
43.6, 41.9, 39.4, 37.7, 34.7, 31.9, 31.7, 25.8, 26.0–25.5 (6C’s, not
well-resolved), 25.1, 24.8, 22.6, 22.5, 18.0, 17.8, 14.1, 14.0, ꢂ4.3,
ꢂ4.4, ꢂ4.7, ꢂ4.8; FTIR (film): 3501, 2956, 2930, 2858, 1734, 1471,
1387, 1363, 1313, 1257, 1082 cmꢂ1; ESIMS: m/z 671.5 ([MþNa]þ).
ESIHRMS calcd for C34H72Si2O7Na ([MþNa]þ): 671.4709; found:
671.4715.
1716, 1471, 1256, 1085 cmꢂ1
;
ESIMS: m/z 641.3 ([MþNa]þ).
ESIHRMS calcd for C32H66Si2O7Na ([MþNa]þ): 641.4245; found:
641.4257.
4.23. Conversion of 30 to 31
A
solution of MNBA (42 mg, 0.122 mmol), DMAP (47 mg,
0.483 mmol), and powdered/activated 4 Å molecular sieves
(450 mg) in dry toluene (28 ml) was stirred at ambient tempera-
ture for 10 min.
A
solution of hydroxyl acid 30 (50 mg,
4.26. Conversion of 32 to 33
0.081 mmol) in dry toluene (12.5 mL) was added slowly (via a sy-
ringe driven by a syringe pump over 5 h). After completion of the
addition, the stirring was continued at ambient temperature for
24 h. The mixture was diluted with Et2O, washed in turn with aq
satd NaHCO3, water, and brine, and dried over anhydrous Na2SO4.
Removal of the solvent on a rotary evaporator and column chro-
2,4,6-Tichlorobenzoyl chloride (114 mL, 0.729 mmol) was added
slowly to a solution of 32 (134 mg, 0.330 mmol), 23 (134 mg,
0.330 mmol), DMAP (189 mg, 1.55 mmol), and powdered/activated
4 Å molecular sieves (300 mg) in dry CH2Cl2 (11 mL) stirred at
ambient temperature under argon. After completion of the addi-
tion, the stirring was continued at ambient temperature until TLC
showed completion of the reaction (ca. 20 h). The mixture was
diluted with Et2O, washed in turn with aq satd NaHCO3, water, and
brine, and dried over anhydrous Na2SO4. Removal of the solvent by
rotary evaporation and column chromatography (40:1 PE/EtOAc)
matography (1:60 PE/EtOAc) on silica gel afforded dilactone 31 as
25
a colorless oil (41 mg, 0.068 mmol, 84%). [
a]
ꢂ56.7 (c 0.5, CHCl3).
D
1H NMR (400 MHz, CDCl3):
d
4.77–4.70 (m, 2H), 4.40–4.34 (m, 2H),
2.63 (dd, J¼13.6, 2.4 Hz, 2H), 2.40 (dd, J¼13.6, 2.4 Hz, 2H), 1.95
(ddd, J¼14.4, 10.1, 4.7 Hz, 2H), 1.76 (ddd, J¼14.4, 8.2, 3.5 Hz, 2H),
1.71–1.67 (m, 2H), 1.52–1.46 (m, 2H), 1.31–1.26 (m, 12H), 0.91 (s,
18H), 0.87 (t, J¼6.6 Hz, 6H), 0.13 (m, 12H). 13C NMR (100 MHz,
CDCl3): 169.4 (2C’s), 72.3 (2C’s), 66.5 (2C’s), 45.5 (2C’s), 42.4 (2C’s),
34.2 (2C’s), 31.6 (2C’s), 25.8 (6C’s), 24.6 (2C’s), 22.5 (2C’s), 18.0
(2C’s), 13.9 (2C’s), ꢂ4.69 (2C’s), ꢂ4.73 (2C’s); FTIR (film): 2956,
1744, 1463, 1281, 1252, 1085 cmꢂ1; ESIMS: m/z 623.3 ([MþNa]þ).
ESIHRMS calcd for C32H64Si2O6Na ([MþNa]þ): 623.4134; found:
623.4141.
on silica gel afforded 33 as a colorless oil (287 mg, 0.277 mmol,
20
84%). [
a
]
ꢂ16.6 (c 1.14, CHCl3). 1H NMR (300 MHz, CDCl3):
d 7.47–
D
7.39 (m, 5H), 5.79–5.70 (dt, J¼11.1, 7.5 Hz, 1H), 5.47 (dd, J¼11.1,
10.0 Hz, 1H), 5.14–5.04 (m, 2H), 4.67 (t, J¼5.6 Hz, 1H), 4.58 (d,
J¼10.8 Hz, 1H), 4.37–4.25 (m, 2H), 4.32 (d, J¼10.8 Hz, 1H), 4.14–4.11
(m, 1H), 3.84–3.80 (m, 1H), 3.43 (s, 3H), 3.42 (s, 3H), 2.66–2.55 (m,
4H), 2.05–2.00 (m, 2H), 2.00–1.76 (m, 4H), 1.73–1.65 (m, 4H), 1.60–
1.48 (m, 4H), 1.44–1.36 (m, 2H), 1.35–1.20 (m, 12H), 0.91 (t, J¼7.8 Hz,
9H), 0.90–0.88 (m, 27H), 0.08–0.06 (m, 18H). 13C NMR (75 MHz,
4.24. Conversion of 31 to verbalactone 13
CDCl3): d 171.1, 170.6, 138.8, 133.4, 130.5, 128.2 (2C’s), 127.7 (2C’s),
127.3, 101.5, 71.4, 71.2, 70.7, 69.6, 66.6, 66.2, 66.1, 52.5, 52.2, 43.0,
42.0 (2C’s), 41.8, 41.3, 39.4, 34.6, 34.2, 31.8, 31.7, 29.9, 26.1–25.6
(9C’s, not well-resolved), 24.8, 24.7, 22.9, 22.5 (2C’s), 17.9 (3C’s), 14.0
(2C’s), 13.8, ꢂ4.4, ꢂ4.6 (2C’s), ꢂ4.7 (2C’s), ꢂ4.8; FTIR (film): 2928,
2857, 1736, 1472, 1387, 1258, 1074 cmꢂ1; ESIMS: m/z 1059.8
([MþNa]þ). ESIHRMS calcd for C57H108Si3O10Na ([MþNa]þ):
1059.7143; found: 1059.7160.
HF$Py (Aldrich, containing w70% HF and 30% Py, 0.36 mL) was
added to a solution of 31 (28 mg, 0.047 mmol) in THF (1.0 mL)
stirred at ambient temperature in a plastic (Nalgene) bottle. After
completion of the addition, the stirring was continued for another
2 h. Aq satd NaHCO3 was introduced, followed by EtOAc. The phases
were separated. The aqueous phase was back-extracted with EtOAc.