T. Baba et al. / Tetrahedron 59 (2003) 6851–6872
6869
and concentrated under reduced pressure. The remaining oil
was chromatographed on a silica gel column (AcOEt–
hexane¼1:4) to give the bicyclic product 74 (165 mg, 93%).
d 11.0, 11.6, 21.2, 30.3, 35.9, 36.1, 37.3, 38.2, 39.5, 56.4,
62.8, 70.6, 71.1, 72.5, 75.1, 75.8, 78.3, 79.5, 116.8, 127.7,
127.8, 128.0, 128.1, 128.2, 128.4, 128.5, 129.2, 130.5,
133.5, 134.5, 136.0, 138.1, 138.2, 139.4, 170.4. Anal. calcd
for C43H54O9S: C, 69.14 H, 7.29. Found: C, 69.11; H, 7.25.
To the solution of 74 (165 mg, 0.160 mmol) in toluene
(7.99 mL) was added bis(trimethylsilyl)acetylene (1.09 mL,
4.79 mmol) and n-Bu3SnH (0.43 mL, 1.60 mmol). After
stirring 30 min at 608C, the reaction mixture was concen-
trated under reduced pressure. The remaining residue was
chromatographed on a silica gel column (AcOEt–
hexane¼9:41) to provide the endocyclic olefin 75
(81.0 mg, 68%) and its C46-epimer 76 (22.0 mg, 19%).
Compound 75. IR (KBr) nmax 3447, 2929, 2876, 2343, 1729,
1455, 1373, 1306, 1245, 1147, 1086, 1028, 915, 748, 699,
607, 532 cm21. 1H NMR (CDCl3, 400 MHz), d 0.87 (3H, d,
J¼7.0 Hz, CH3), 0.88 (3H, d, J¼7.0 Hz, CH3), 1.43 (1H,
ddd, J¼12.0, 11.5, 11.0 Hz, H-43a), 1.55–1.60 (1H, m,
H-50), 1.79–1.93 (4H, m, –OH, H-51, 53a, 53b), 1.98 (3H, s,
–OCOCH3), 2.00–2.08 (1H, m, H-40a), 2.53–2.56 (1H, m,
H-40b), 2.59 (1H, dt, J¼12.0, 4.0 Hz, H-43b), 2.75 (1H, dd,
J¼9.0, 8.5 Hz, H-45), 3.05 (1H, m, H-41), 3.08 (1H, td,
J¼9.0, 2.5 Hz, H-46), 3.10 (1H, dd, J¼13.5, 10.5 Hz,
H-58a), 3.18 (1H, ddd, J¼11.0, 9.0, 4.5 Hz, H-42), 3.34
(1H, ddd, J¼11.5, 8.5, 4.5 Hz, H-44), 3.54 (1H, m, H-54),
3.59 (1H, ddd, J¼11.5, 6.5, 4.5 Hz, H-55a), 3.79 (1H, ddd,
J¼11.5, 6.5, 4.5 Hz, H-55b), 3.84 (1H, dd, J¼13.5, 1.5 Hz,
H-58b), 3.90 (1H, br, H-49), 4.42 (1H, d, J¼11.5 Hz,
–OCH2Ph), 4.54 (1H, d, J¼11.5 Hz, –OCH2Ph), 4.58 (1H,
d, J¼11.5 Hz, –OCH2Ph), 4.62 (1H, d, J¼11.5 Hz,
–OCH2Ph), 4.92–5.04 (3H, m, H-52, 57), 5.62–5.73 (1H,
m, H-39), 5.83 (1H, ddd, J¼11.5, 4.5, 3.5 Hz, H-48), 5.93
(1H, ddd, J¼11.5, 3.5, 2.0 Hz, H-47), 7.20–7.38 (10H, m,
aromatic), 7.52–7.56 (2H, m, aromatic), 7.62–7.66 (1H, m,
aromatic), 7.88–7.91 (2H, m, aromatic). 13C NMR (CDCl3,
100 MHz), d 36.7, 37.0, 37.6, 37.9, 38.4, 38.5, 39.1, 39.4,
39.6, 39.7, 57.0, 57.2, 63.3, 64.2, 70.7, 70.8, 70.9, 70.9,
71.2, 72.3, 72.9, 73.0, 75.8, 75.8, 76.8, 77.1, 77.2, 77.5,
77.8, 78.9, 79.1, 79.4, 79.5, 79.6, 80.5, 81.3, 116.8, 116.9,
127.7, 127.8, 127.9, 127.9, 128.0, 128.0, 128.1, 128.2,
128.4, 128.5, 128.6, 128.9, 129.1, 131.0, 131.9, 133.6,
135.1, 135.6, 135.8, 138.1, 138.1, 138.1, 138.2, 140.1,
170.4, 170.8. Anal. calcd for C43H54O9S: C, 69.14 H, 7.29.
Found: C, 69.11; H, 7.25. Compound 76. 1H NMR (CDCl3,
400 MHz), d 0.89 (3H, d, J¼7.0 Hz, CH3), 0.90 (3H, d,
J¼6.5 Hz, CH3), 1.38 (1H, q, J¼11.0 Hz, H-43a), 1.43–1.51
(1H, m, H-50), 1.77–2.00 (4H, m, –OH, H-51, 53a, 53b),
2.00 (3H, s, –OCOCH3), 2.03–2.12 (1H, m, H-40a), 2.43
(1H, m, H-40b), 2.66 (1H, dt, J¼11.5, 4.0 Hz, H-43b), 3.05
(1H, dddd, J¼11.0, 8.0, 4.5, 2.0 Hz, H-46), 3.09–3.16 (2H,
m, H-41, 42), 3.16 (1H, dd, J¼9.5, 4.5 Hz, H-45), 3.34 (1H,
ddd, J¼11.5, 9.0, 4.5 Hz, H-44), 3.40 (1H, dd, J¼14.0,
11.0 Hz, H-58a), 3.48 (1H, dq, J¼8.0, 4.0 Hz, H-54), 3.60
(1H, dd, J¼14.0, 2.0 Hz, H-58b), 3.62 (1H, ddd, J¼12.0,
7.5, 4.0 Hz, H-55a), 3.81 (1H, ddd, J¼12.0, 5.0, 4.0 Hz, H-
55b), 4.04 (1H, td, J¼4.0, 2.5 Hz, H-49), 4.42 (1H, d,
J¼11.5 Hz, –OCH2Ph), 4.55 (1H, d, J¼11.5 Hz,
–OCH2Ph), 4.58 (1H, d, J¼11.5 Hz, –OCH2Ph), 4.62 (1H,
d, J¼11.5 Hz, –OCH2Ph), 4.92–4.98 (2H, m, H-57), 5.08
(1H, ddd, J¼10..0, 5.5, 2.5 Hz, H-52), 5.54–5.64 (1H, m,
H-39), 5.70 (1H, dd, J¼11.5, 4.0 Hz, H-48), 5.91 (1H, ddd,
J¼11.5, 8.0, 2.0 Hz, H-47), 7.25–7.38 (10H, m, aromatic),
7.51–7.58 (2H, m, aromatic), 7.61–7.65 (1H, m, aromatic),
7.88–7.91 (2H, m, aromatic). 13C NMR (CDCl3, 100 MHz),
5.1.34. Ketone 79. To a solution of endocyclic olefin 75
(118 mg, 0.16 mmol) in THF (1.58 mL) and MeOH
(1.58 mL) was treated with K2CO3 (39 mg, 0.28 mmol)
overnight at room temperature. The reaction mixture was
poured into saturated NH4Cl solution and extracted with
AcOEt (£3). The organic layer was dried over Na2SO4 and
concentrated under reduced pressure. The remaining residue
was chromatographed on a silica gel column (AcOEt–
hexane¼2:3) to provide diol 77 (104 mg, 93%).
To a solution of the diol 77 (104 mg, 0.15 mmol) in CH2Cl2
(1.48 mL) were added Et3N (206 mL, 1.48 mmol), DMAP
(18 mg, 0.15 mmol), and TBSCl (111 mg, 0.74 mmol) at
08C. After stirring for 3 h at room temperature, the reaction
mixture was poured into cold saturated NH4Cl solution,
extracted with Et2O (£3), and washed with brine. The
organic layer was dried over Na2SO4 and concentrated
under reduced pressure. The remaining crude oil was
chromatographed on a silica gel column (AcOEt–
hexane¼1:4) to provide silyl ether 78 (114 mg, 94%).
To a solution of silyl ether 78 (114 mg, 0.14 mmol) in
DMSO (1.39 mL) was added IBX (78 mg, 0.28 mmol) at
room temperature. After stirring for 4 h, the reaction
mixture was added H2O and filtered through Hyflo-Super-
Celw. After the filter cake was washed with Et2O, the
organic phase of the filtrate was dried over Na2SO4 and
concentrated under reduced pressure. The remaining crude
oil was chromatographed on a silica gel column (AcOEt–
hexane¼1:4) to provide ketone 79 (111 mg, 98%). Com-
pound 79. IR (KBr) nmax 3066, 2929, 2858, 1712, 1455,
1307, 1252, 1087, 837, 748, 698, 565, 533 cm21. 1H NMR
(CDCl3, 400 MHz), d 0.05 (3H, s, –Si(CH3)2), 0.06 (3H, s,
–Si(CH3)2), 0.86 (3H, d, J¼7.0 Hz, CH3-59), 0.89 (9H, s,
–SiC(CH3)3), 1.02 (3H, d, J¼7.0 Hz, CH3-60), 1.38 (1H, dt,
J¼12.0, 11.0 Hz, H-43a), 1.92–2.05 (2H, m, H-40a, 50),
2.45 (1H, dt, J¼12.0, 4.5 Hz, H-43b), 2.49–2.56 (1H, m,
H-40b), 2.63–2.81 (5H, m, H-45, 46, 51, 53a, 53b), 2.96–
3.09 (3H, m, H-41, 42, 44), 3.10 (1H, dd, J¼14.0, 10.0 Hz,
H-58a), 3.59 (1H, dd, J¼10.5, 5.5 Hz, H-55a), 3.70 (1H, dd,
J¼10.5, 5.0 Hz, H-55b), 3.76 (1H, dd, J¼14.0, 2.0 Hz,
H-58b), 3.81 (1H, ddd, J¼6.0, 4.0, 2.0 Hz, H-49), 4.06 (1H,
dt, J¼7.5, 4.5 Hz, H-54), 4.34 (1H, d, J¼11.5 Hz,
–OCH2Ph), 4.55 (1H, d, J¼11.5 Hz, –OCH2Ph), 4.56 (1H,
d, J¼11.0 Hz, –OCH2Ph), 4.65 (1H, d, J¼11.0 Hz,
–OCH2Ph), 4.94–5.03 (2H, m, H-57), 5.61–5.74 (2H, m,
H-39, 47), 5.90 (1H, ddd, J¼11.5, 3.0, 2.5 Hz, H-48), 7.20–
7.36 (10H, m, aromatic), 7.52–7.57 (2H, m, aromatic),
7.61–7.66 (1H, m, aromatic), 7.84–7.91 (2H, m, aromatic).
13C NMR (CDCl3, 100 MHz), d 10.9, 13.7, 18.3, 25.9, 36.1,
36.8, 39.6, 44.6, 48.5, 57.3, 64.7, 70.9, 72.9, 75.0, 76.0, 78.0,
78.7, 79.3, 79.7, 116.8, 127.6, 127.7, 128.0, 128.3, 129.1,
130.6, 133.5, 134.9, 135.1, 138.1, 138.7, 140.0. Anal. calcd for
C47H64O8SSi: C, 69.08 H, 7.89. Found: C, 69.07; H, 7.87.
5.1.35. Diketone 80. To a solution of ketone 79 (71 mg,
0.087 mmol) in DMF (1.58 mL) and H2O (158 mL) was