2790
F. Bilodeau et al. / Tetrahedron 59 (2003) 2781–2791
OCH2C(CH3)). 13C NMR (75 MHz, CDCl3) d (ppm) 208.5,
207.9, 170.1, 169.2, 135.5, 134.3, 133.4, 132.7, 131.5,
131.0, 129.6, 128.9, 128.6, 127.6, 99.2, 98.9, 81.0, 76.5,
74.8, 70.3, 69.9, 61.7, 60.7, 60.2, 40.3, 39.9, 31.1, 30.7,
29.4, 28.8, 27.9, 27.5, 26.9, 21.0, 20.5, 19.3, 18.4, 18.2. IR
(film) n 3072, 2932, 2858, 1732, 1709, 1472, 1428, 1368,
1248, 1226, 1198, 1160, 1113, 1069, 998, 824, 758, 703. MS
(EI): 643 (Mþ2C4H9). HRMS (Mþ2C4H9) calcd for
C39H51SiO6: 643.3455; found: 643.3472^0.0019.
70.1, 62.1, 53.1, 45.6, 41.8, 39.7, 30.0, 29.2, 28.5, 24.5,
20.9, 19.6, 18.6. IR (film) n 3448, 2933, 2860, 1707, 1458,
1380, 1249, 1198, 1159, 1122, 1070, 998, 864, 759. MS
(EI): 347 (Mþ2CH3). HRMS (Mþ2CH3) calcd for
C21H31O4: 347.2222; found: 347.2229^0.0010.
To a solution of the previous alcohol (44 mg, 0.12 mmol) in
dichloromethane (7 mL) at room temperature was added
Dess–Martin periodinane (154 mg, 0.36 mmol). The sol-
ution was stirred for 1 h after which diethyl ether (5 mL) and
a saturated aqueous solution of sodium bicarbonate (5 mL)
were added. Solid sodium thiosulfate pentahydrated
(214 mg, 1.08 mmol) was also added and the resulting
mixture was stirred until cloudiness has disappeared. The
clear solution was then extracted using diethyl ether
(3£15 mL). The combined organic phases were washed
with brine, dried over magnesium sulfate, filtered and
concentrated. The residue was purified by flash chromato-
graphy (40% ethyl acetate in hexanes) to give aldehyde 31
as a white solid (35 mg, 80%, mp¼157–1648C).
[a]2D3¼þ96.88 (c¼1.06, CHCl3). 1H NMR (300 MHz,
CDCl3) d (ppm) 10.06 (1H, s, CHO), 6.2–5.9 and 5.6–5.5
(4H, m, CHvCHCHvCH), 3.77 (1H, t, J¼6.4 Hz,
OCH(CH2)), 3.66 (1H, d, J¼11.4 Hz) and 3.46 (1H, d,
J¼11.4 Hz) (OCH2C(CH3)), 2.7–2.0 (9H, m, (CH2)2-
CO(CH2)2 and CHHC(CH3)v), 2.15 (3H, s, C(CH3)v),
1.97 (1H, td, J¼13.3, 4.0 Hz, CHHC(CH3)v), 1.8–1.4 (2H,
m, OCH(CH2)), 1.44 (3H, s) and 1.43 (3H, s) (C(CH3)2),
0.89 (3H, s, OCH2C(CH3)). 13C NMR (75 MHz, CDCl3) d
(ppm) 212.2, 191.3, 159.8, 135.7, 134.5, 133.1, 129.7,
128.9, 99.1, 75.3, 70.1, 45.7, 41.2, 39.4, 31.5, 30.0, 29.0,
27.7, 19.8, 19.2, 17.9. IR (film) n 2991, 2936, 2860, 1708,
1662, 1446, 1378, 1306, 1249, 1198, 1122, 1082, 1000, 892,
755. MS (EI): 345 (Mþ2CH3). HRMS (Mþ2CH3) calcd
for C21H29O4: 345.2066; found: 345.2069^0.0010.
5.2.5. Macrocycle 30. To a solution of compound 29
(54 mg, 0.078 mmol) in toluene (10 mL) was added
triethylamine (216 mL, 1.55 mmol). This solution was
transferred into a pre-conditioned pyrex tube (washed
3£NH4OH conc., 3£H2O, 3£acetone and flame dried) and
was degassed 3 times (tube freezing in liquid nitrogen under
nitrogen, then degassing under vacuum while letting the
tube warming-up to room temperature). The tube was then
sealed under vacuum and allowed to warm-up to room
temperature. The tube was finally heated to 1908C for 15 h
after which it was broken and rinsed with dichloromethane
(4£10 mL). The solvents were evaporated and the residue
was purified by flash chromatography (10% ethyl acetate in
hexanes) to give compound 30 as a clear oil (32 mg, 68%).
[a]2D3¼þ39.28 (c¼1.28, CHCl3). 1H NMR (300 MHz,
CDCl3) d (ppm) 7.68 (4H, m) and 7.39 (6H, m) (2£Ph
(TBDPS)),
6.2–5.9
and
5.7–5.6
(4H,
m,
CHvCHCHvCH), 4.17 (1H, d, J¼12.1 Hz) and 4.09
(1H, d, J¼12.1 Hz) (CH2OTBDPS), 3.7–3.6 (1H, m,
OCH(CH2)), 3.58 (1H, d, J¼11.4 Hz) and 3.46 (1H, d,
J¼11.4 Hz) (OCH2C(CH3)), 2.5–2.2 (8H, m, CH2CH2-
COCH2CH2), 2.01 (1H, td, J¼13.1, 4.6 Hz) and 1.80 (1H,
td, J¼13.1, 4.6 Hz) (CH2C(CH3)v), 1.45 (3H, s,
C(CH3)v), 1.42 (6H, s, C(CH3)2), 1.4–1.2 (2H, m,
OCH(CH2)), 1.02 (9H, s, SiC(CH3)3), 0.92 (3H, s, OCH2-
C(CH3)). 13C NMR (75 MHz, CDCl3) d (ppm) 213.2, 135.6,
134.8, 134.5, 133.1, 130.6, 129.6, 129.6, 129.0, 127.7,
127.6, 99.0, 75.7, 70.1, 62.7, 45.7, 41.6, 39.8, 29.9, 29.4,
29.3, 28.4, 26.8, 26.6, 23.2, 19.8, 18.8, 18.5. IR (film) n
3071, 2956, 2931, 2857, 1709, 1472, 1428, 1382, 1198,
1112, 1070, 998, 824, 757, 703. MS (EI): 585 (Mþ2CH3).
HRMS (Mþ2CH3) calcd for C37H49SiO4: 585.3400; found:
585.3408^0.0017.
5.2.7. Tetracycle 32. To a solution of compound 31 (11 mg,
0.031 mmol) in toluene (3 mL) was added triethylamine
(60 mL, 0.41 mmol). This solution was transferred into a
pre-conditioned quartz tube (washed 3£NH4OH conc.,
3£H2O, 3£acetone and flame dried) and was degassed 3
times (tube freezing in liquid nitrogen under nitrogen, then
degassing under vacuum while letting the tube warming-up
to room temperature). The tube was then sealed under
vacuum and allowed to warm-up to room temperature. The
tube was finally heated to 2508C for 48 h after which it was
broken and rinsed with dichloromethane (4£10 mL). The
solvents were evaporated and the residue was purified by
flash chromatography (50% ethyl acetate in hexanes) to give
compound 32 as a white solid (9 mg, 77%, mp¼213–
5.2.6. Macrocycle-aldehyde 31. To a solution of protected
alcohol 30 (95 mg, 0.16 mmol) in tetrahydrofuran (7 mL) at
08C was added slowly the tetrabutylammonium fluoride
(789 mL, 0.79 mmol, 1.0 M in THF). The solution was then
allowed to warm-up to room temperature and it was stirred
for 24 h before being concentrated and directly purified by
flash chromatography (60% ethyl acetate in hexanes) to give
the corresponding alcohol as a clear oil (44 mg, 77%).
[a]2D3¼þ54.88 (c¼1.62, CHCl3). 1H NMR (300 MHz,
2188C).
Recrystallization
system:
EtOAc/hexanes
[a]2D3¼276.88 (c¼1.16, CHCl3). 1H NMR (300 MHz,
CDCl3) d (ppm) 5.79 (1H, dAB, J¼9.3 Hz) and 5.69 (1H,
dt, J¼9.3, 3.6 Hz) (CHvCH), 4.33, (1H, m, CHOH), 3.73
(1H, m, OCH(CH2)), 3.50 (1H, d, J¼12.0 Hz) and 3.43 (1H,
d, J¼12.0 Hz) (OCH2C(CH3)), 2.8–2.6 (2H, m), 2.5–2.3
(3H, m), 2.19 (1H, td, J¼13.3, 3.6 Hz), 2.1–1.2 (7H, m)
(CH and CH2), 1.45 (3H, s) and 1.43 (3H, s) (C(CH3)2), 1.01
(3H, s, (CH2)2C(CH3)), 0.92 (3H, s, OCH2C(CH3)). 13C
NMR (75 MHz, CDCl3) d (ppm) 214.9, 133.3, 129.4, 97.8,
78.8, 72.0, 69.4, 57.0, 50.0, 41.1, 38.9, 37.8, 35.5, 33.6,
30.5, 30.0, 27.6, 27.1, 23.6, 19.7, 19.0, 18.7. IR (film) n
3388, 2991, 2936, 2871, 1704, 1459, 1378, 1252, 1201,
CDCl3)
d
(ppm) 6.2–6.0 and 5.6 (4H, m,
CHvCHCHvCH), 4.10 (1H, d, J¼11.7 Hz) and 4.01
(1H, d, J¼11.7 Hz) (CH2OH), 3.7 (1H, m, OCH(CH2)), 3.59
(1H, d, J¼11.4 Hz) and 3.47 (1H, d, J¼11.4 Hz) (OCH2-
C(CH3)), 2.6–2.1 (8H, m, (CH2)2CO(CH2)2), 2.09 (1H, td,
J¼13.3, 4.6 Hz) and 1.80 (1H, td, J¼13.3, 4.6 Hz) (CH2-
C(CH3)v), 1.71 (3H, s, C(CH3)v), 1.42 (3H, s) and 1.41
(3H, s) (C(CH3)2), 1.4–1.2 (2H, m, OCH(CH2)), 0.90 (3H,
s, OCH2C(CH3)). 13C NMR (75 MHz, CDCl3) d (ppm)
213.1, 135.4, 134.6, 133.1, 131.1, 129.5, 128.9, 99.0, 75.5,