mmax/cm−1 (film) 3400, 2933, 1709, 1458, 1351, 1193, 1074, 901; dH
(500 MHz, C6D6) – major anomer only – 6.08 (1 H, d, J 16.2 Hz,
131.4, 130.4, 131.2, 114.3, 101.3, 76.2, 75.5, 74.7, 73.1, 72.2, 72.1,
69.9, 69.8, 69.7, 51.1, 47.4, 44.9, 43.7, 40.2, 39.7, 33.9, 33.1, 32.6,
29.2, 28.6, 26.1, 26.1, 26.1, 26.0, 25.0, 23.9, 23.2, 18.5, 18.4, 18.3,
18.3, 16.7, 16.1, 14.3, 11.9, −3.8, −4.0, −4.0, −4.1, −4.1, −4.3,
−4.4, −4.9; HRMS (ES+) m/z calc. for C67H134O12Si5Na ([MNa]+):
1293.8613, found: 1293.8600.
=
5-H), 5.73 (1 H, s, 6 CH2), 5.69 (1 H, dd, J 16.2, 7.2 Hz, 4-H),
=
5.24 (1 H, d, J 9.9 Hz, 11-H), 5.14 (1 H, s, 6 CH2), 5.05 (1 H, d,
J 9.3 Hz, 7-H), 4.91–4.96 (1 H, m, 25-H), 4.67 (1 H, br d, J 4.4 Hz,
3-OH), 4.58–4.61 (1 H, m, 3-H), 4.53 (1 H, br s, 14-OH), 4.00–
4.06 (3 H, m, 16-H, 19-H and 21-H), 3.88 (1 H, br s, 16-OH), 3.77
(1 H, ddd, J 7.1, 6.1 and 2.7 Hz, 14-H), 3.52–3.55 (1 H, m, 24-
H), 3.49–3.51 (2 H, m, 7-OH and 15-OH), 3.26 (1 H, dd, J 18.5,
2.7 Hz, 8-H), 2.80 (1 H, dq, J 9.9, 6.7 Hz, 10-H), 2.62 (1 H, qd,
J 7.1, 2.2 Hz, 2-H), 2.58 (1 H, dd, J 14.4, 6.1 Hz, 13-H), 2.48
(1 H, dd, J 14.4, 7.1 Hz, 13-H), 2.29 (1 H, dd, J 18.5, 9.3 Hz, 8-H),
2.06–2.12 (1 H, m, 17-H), 1.80–1.87 (2 H, m, 17-H and 18-H), 1.53
(3 H, s, 12-CH3), 1.15–1.63 (11 H, m, 20-H, 20-H, 22-H, 22-H,
23-H, 26-H, 26-H, 27-H, 27-H, 28-H and 28-H), 1.11 (3 H, d,
J 6.7 Hz, 10-CH3), 1.08 (3 H, d, J 7.1 Hz, 2-CH3), 1.03–1.12 (2 H,
m, 18-H and 23-H), 0.86 (3 H, t, J 6.8 Hz, 28-CH3); dC (125 MHz,
C6D6) – major anomer only – 212.0 (C9), 173.6 (C1), 147.2 (C6),
Acid 80
Methyl ester 79 (0.83 g, 0.650 mmol) was dissolved in 1,2-
dichloroethane (20 mL) in a 50 mL round-bottomed flask and
Me3SnOH (1.18 g, 6.50 mmol) was added. The reaction vessel was
then sealed under argon, and the stirred mixture was heated to
80 ◦C. Additional portions of Me3SnOH (1.18 g, 6.50 mmol) were
added every 12 h over a period of two days. Twelve hours after
the final addition, the reaction was cooled to room temperature,
R
diluted with EtOAc, filtered through a pad of Celiteꢀ, and the
filtrate was concentrated in vacuo. The residue was purified by
flash chromatography on silica gel (15% EtOAc in hexanes) to
give 80 (0.365 g, 45%, 66% based on recovered starting material
79) as a highly viscous, light yellow oil. Rf = 0.36 (silica gel, 3 :
2 hexanes–Et2O); [a]2D5 +33.8◦ (c 7.70 in CH2Cl2); mmax/cm−1 (film)
3493, 2955, 2890, 1745, 1711, 1471, 1361, 1092, 835; dH (500 MHz,
C6D6) 6.30 (1 H, d, J 16.1 Hz, 5-H), 6.10 (1 H, dd, J 16.1, 6.4 Hz,
=
136.7 (C12), 131.2 (C5), 128.5 (C4), 125.2 (C11), 114.5 (6 CH2),
96.1 (C15), 81.6 (C24), 77.2 (C25), 76.8 (C14), 75.1 (C21), 75.0
(C3), 67.2 (C7), 66.7 (C16), 66.5 (C19), 48.2 (C2), 47.7 (C8), 47.3
(C10), 42.5 (C20), 41.4 (C13), 31.9 (C22), 31.0 (C26), 27.5 (C27),
27.4 (C23), 26.5 (C17), 25.6 (C18), 22.8 (C28), 17.3 (12-CH3), 14.9
(10-CH3), 14.1 (2-CH3), 9.4 (28-CH3); HRMS (ES+) m/z calc. for
C33H52O10Na ([MNa]+): 631.3452, found: 631.3459.
=
=
4-H), 5.48 (1 H, s, 6 CH2), 5.12 (1 H, s, 6 CH2), 5.06 (1 H, d,
J 9.9 Hz, 11-H), 5.02 (1 H, d, J 9.0 Hz, 7-H), 4.63 (1 H, app t,
J 5.0 Hz, 3-H), 4.16 (1 H, d, J 10.0 Hz, 14-H), 4.07–4.11 (1 H, 16-
H), 3.96–4.01 (2 H, m, 19-H and 21-H), 3.60 (1 H, app t, J 9.1 Hz,
9-H), 3.52–3.57 (2 H, m, 24-H and 25-H), 2.67 (1 H, d, J 13.1 Hz,
13-H), 2.49–2.54 (1 H, m, 2-H), 2.30–2.37 (1 H, m, 10-H), 2.21–
2.25 (1 H, m, 13-H), 2.06–2.16 (1 H, m, 17-H), 1.87–1.97 (4 H, m,
8-H, 17-H, 18-H and 22-H), 1.56–1.81 (9 H, m, 8-H, 18-H, 20-H,
20-H, 22-H, 23-H, 26-H, OH and OH), 1.51 (3 H, s, 12-CH3),
1.47–1.53 (2 H, m, 26-H and 27-H), 1.41 [3 H, s, O2C(CH3)2], 1.37
[3 H, s, O2C(CH3)2], 1.30–1.44 (4 H, m, 23-H, 27-H, 28-H and
28-H), 1.25 (3 H, d, J 6.9 Hz, 2-CH3), 1.06 [9 H, s, SiC(CH3)3],
1.04 [9 H, s, SiC(CH3)3], 1.03 [9 H, s, SiC(CH3)3], 1.01 [9 H, s,
SiC(CH3)3], 0.96 [9 H, s, SiC(CH3)3], 0.91–0.94 (6 H, m, 10-CH3
and 28-CH3), 0.25 (3 H, s, SiCH3), 0.19 (3 H, s, SiCH3), 0.19
(3 H, s, SiCH3), 0.18 (3 H, s, SiCH3), 0.18 (3 H, s, SiCH3), 0.17
(3 H, s, SiCH3), 0.14 (3 H, s, SiCH3), 0.13 (3 H, s, SiCH3), 0.11
(3 H, s, SiCH3), 0.09 (3 H, s, SiCH3); dC (125 MHz, C6D6) 210.0,
179.3, 149.7, 133.5, 131.2, 130.9, 128.5, 114.4, 101.3, 76.1, 75.0,
74.7, 73.1, 72.2, 72.1, 69.9, 69.8, 47.2, 44.9, 43.6, 40.1, 39.6, 33.8,
33.1, 32.5, 29.1, 28.5, 26.2, 26.2, 26.1, 26.1, 26.0, 24.9, 23.9, 23.9,
23.2, 18.5, 18.4, 18.3, 18.3, 16.7, 16.2, 14.3, 11.1, −3.8, −3.9, −4.0,
−4.0, −4.1, −4.1, −4.3, −4.4, −4.8, −4.9; HRMS (ES+) m/z calc.
for C66H132O12Si5Na ([MNa]+): 1279.8479, found: 1279.8474.
Diol 79
To a vigorously stirred solution of ketone 71 (1.45 g, 0.96 mmol)
in 2 : 1 CH2Cl2–aqueous pH 7.0 buffer (15 mL) was added DDQ
(0.68 g, 3.0 mmol) in one portion at 0 ◦C. After 20 min the reaction
was quenched by the addition of sat. aq. NaHCO3 (15 mL), and
extracted with Et2O (3 × 20 mL). The combined organic layers
were washed with sat. aq. NaHCO3 (1 × 20 mL), brine (1 × 20 mL),
dried (MgSO4), filtered and concentrated in vacuo. The residue
was purified by flash chromatography on silica gel (gradient: 5–
15% Et2O in hexanes) to give 79 (0.96 g, 78%) as a viscous, yellow
oil. Rf = 0.19 (silica gel, 4 : 1 hexanes–Et2O); [a]25 +36.5◦ (c 1.41
D
in CH2Cl2); mmax/cm−1 (film) 3510, 2956, 2859, 1746, 1738, 1382,
1172, 939; dH (500 MHz, C6D6) 6.29 (1 H, d, J 16.2 Hz, H-5),
=
6.11 (1 H, dd, J 16.2, 6.8 Hz, H-4), 5.48 (1 H, s, 6 CH2), 5.11
=
(1 H, s, 6 CH2), 5.03–5.07 (2 H, m, H-7 and H-11), 4.55 (1 H,
dd, J 6.8, 5.3 Hz, H-3), 4.16 (1 H, dd, J 11.0, 2.5 Hz, H-14),
4.10 (1 H, dd, J 6.8, 4.1 Hz, H-16), 3.97–4.03 (2 H, m, H-19 and
H-21), 3.53–3.63 (3 H, m, H-9, H-24 and H-25), 3.43 (3 H, s,
CO2CH3), 2.68 (1 H, dd, J 13.9, 2.5 Hz, H-13), 2.51–2.57 (2 H,
m, H-2 and OH), 2.28–2.37 (1 H, m, H-10), 2.24 (1 H, dd, J 13.9,
11.0 Hz, H-13), 2.10–2.17 (1 H, m, H-17), 1.89–1.98 (4 H, m, H-8,
H-17, H-23 and OH), 1.68–1.84 (5 H, m, H-8, H-18, H-20, H-26
and H-26), 1.55–1.67 (4 H, m, H-18, H-20, H-22 and H-23), 1.50
(3 H, s, 12-CH3), 1.41 [3 H, s, O2C(CH3)2], 1.36 [3 H, s, O2C(CH3)2],
1.27 (3 H, d, J 7.0 Hz, 2-CH3), 1.32–1.53 (5 H, m, H-22, H-27,
H-27, H-28 and H-28), 1.07 [9 H, s, SiC(CH3)3], 1.04 [9 H, s,
SiC(CH3)3], 1.03 [9 H, s, SiC(CH3)3], 0.99 [9 H, s, SiC(CH3)3],
0.96 [9 H, s, SiC(CH3)3], 0.91–0.94 (6 H, m, 10-CH3 and 28-CH3),
0.26 (3 H, s, SiCH3), 0.20 (3 H, s, SiCH3), 0.19 (3 H, s, SiCH3),
0.19 (3 H, s, SiCH3), 0.18 (3 H, s, SiCH3), 0.16 (3 H, s, SiCH3),
0.14 (3 H, s, SiCH3), 0.10 (3 H, s, SiCH3), 0.09 (3 H, s, SiCH3), 0.08
(3 H, s, SiCH3); dC (150 MHz, C6D6) 209.9, 173.9, 149.8, 133.5,
Macrolactone 81
To a stirred solution of carboxylic acid 80 (0.160 g, 0.127 mmol)
and Et3N (0.71 mL, 5.08 mmol) in toluene (8 mL) was added
2,4,6-trichlorobenzoyl chloride 74 (0.60 mL, 3.81 mmol) at room
temperature. After stirring for 16 h, the solution was diluted with
an additional portion of toluene (10 mL) and then added dropwise
via syringe pump to a stirred solution of 4-DMAP (0.480 g,
3.81 mmol) in toluene (200 mL) over 6 h. After stirring for a
further 16 h at room temperature, the reaction was quenched by
2180 | Org. Biomol. Chem., 2006, 4, 2158–2183
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The Royal Society of Chemistry 2006
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