M. Ojika et al. / Tetrahedron 63 (2007) 3138–3167
3149
0.95 (3H, d, J¼7.0 Hz), 1.09 (3H, d, J¼7.0 Hz), 1.11 (3H, d,
J¼7.0 Hz), 1.24–1.66 (11H, m), 1.48 (3H, s), 1.68 (1H, m),
1.78 (1H, m), 1.84 (1H, m), 1.94–2.04 (2H, m), 1.99 (3H, s),
2.01 (3H, s), 2.02 (3H, s), 2.03 (3H, s), 2.07 (3H, s), 2.11
(1H, m), 2.18 (1H, m), 2.20–2.34 (3H, m), 2.42 (1H, ddd,
J¼14.0, 7.0, 7.0 Hz), 2.51 (1H, m), 3.14 (3H, s), 3.22 (3H,
s), 3.33 (1H, t, J¼7.0 Hz), 3.56 (1H, dt, J¼8.0, 7.0 Hz),
3.73 (1H, m), 3.80 (1H, d, J¼1.0 Hz), 4.57 (2H, d,
J¼6.4 Hz), 4.68 (1H, m), 4.79 (1H, dd, J¼9.6, 3.2 Hz),
4.88 (1H, dd, J¼9.2, 2.0 Hz), 5.01 (1H, ddd, J¼7.0, 7.0,
1.5 Hz), 5.28 (1H, dd, J¼15.0, 8.0 Hz), 5.30 (1H, m), 5.40
(1H, d, J¼4.8 Hz), 5.53 (1H, dt, J¼15.0, 7.0 Hz), 5.60–
5.70 (2H, m), 6.06 (1H, dd, J¼15.6, 10.6 Hz), 6.25 (1H,
dd, J¼15.2, 10.6 Hz); HRMS (FAB) (NaI) found m/z
983.6055, calcd for C54H88O14Na (M+Na)+ 983.6071.
OMe), 4.03 (1H, m, H5), 4.23 (1H, ddd, J¼10.8, 6.0,
5.0 Hz, H5), 4.88 (1H, ddd, J¼9.2, 8.5, 2.5 Hz, H7), 4.93
(1H, dd, J¼8.3, 3.0 Hz, H9), 5.01 (1H, dq, J¼3.5, 6.7 Hz,
H14), 6.83 (1H, br s, NH), 6.89 (1H, br s, NH), 7.30 (4H,
m, ArH), 7.40 (4H, d, J¼8.5 Hz, ArH); HRMS (FAB) found
m/z 757.1361, calcd for C32H4379Br2N2O9 (M+H)+
757.1335.
C15–C20 fragment 12: colorless powder, [a]1D7 ꢁ1.6 (c 0.13,
CHCl3); UV (MeOH) lmax 244 nm (3 42,000); IR (CHCl3)
3430, 1730, 1595, 1520, 1070 cmꢁ1 1H NMR (CDCl3,
;
500 MHz) d 1.00 (3H, d, J¼6.7 Hz, 17-Me), 1.47 (1H,
ddd, J¼14.0, 7.0, 7.0 Hz, H18), 1.55 (1H, ddd, J¼14.0,
6.4, 6.4 Hz, H18), 1.63 (1H, m, H16), 1.70 (1H, m, H16),
1.78 (1H, m, H17), 3.43 (3H, s, OMe), 3.52 (1H, m, H19),
4.10 (1H, dd, J¼11.8, 5.2 Hz, H20), 4.21 (1H, dt, J¼11.0,
6.1 Hz, H15), 4.26 (1H, dt, J¼11.0, 6.5 Hz, H15), 4.38
(1H, dd, J¼11.8, 3.1 Hz, H20), 6.85 (1H, br s, NH), 6.93
(1H, br s, NH), 7.26 (2H, d, J¼8.9 Hz, ArH), 7.27 (2H, d,
J¼8.9 Hz, ArH), 7.38 (2H, d, J¼8.9 Hz, ArH), 7.39 (2H,
d, J¼8.9 Hz, ArH); HRMS (FAB) found m/z 557.0294, calcd
for C22H2779Br2N2O5 (M+H)+ 557.0287.
4.3.6. Fragments 11–13. To a solution of 10 (3.4 mg,
0.0035 mmol) in dry pyridine (0.34 mL) was added
a 0.4 M solution of OsO4 in dry THF (0.045 mL,
0.018 mmol), and the mixture was stirred at 0 ꢂC for 1.5 h.
The reaction was quenched by adding a mixture of sodium
hydrogensulfite (60 mg), pyridine (0.85 mL), and water
(1 mL). The mixture was stirred for 30 min, diluted with
water (3 mL), and extracted with three 4-mL portions of
EtOAc. The combined organic layers were concentrated to
give an oil, which was dissolved in EtOH (0.6 mL). To the
ethanolic solution was added a solution of sodium periodate
(10 mg, 0.047 mmol) in water (0.3 mL), and the mixture was
stirred at room temperature for 2 h. The reaction mixture was
diluted with water (3 mL) and extracted with ether (4 mL)
four times. The combined organic layers were concentrated
to a small volume, which was diluted with MeOH (1 mL)
and acetic acid (0.05 mL). The resulting solution was added
with stirring sodium cyanoborohydride (12 mg, 0.19 mmol)
in three portions over 10 min. After an additional stirring for
15 min, the reaction mixture was concentrated, and the resi-
due was dissolved in water (4 mL) and extracted with four
4-mL portions of ether. The combined organic layers were
concentrated to give an oily material, which was dissolved
in dry pyridine (0.6 mL). The mixture was stirred with p-
bromophenyl isocyanate (100 mg, 0.51 mg) at room temper-
ature for 1 h. The reaction was quenched by adding water
(0.05 mL). The mixture was stirred for 10 min, concen-
trated, and suspended in ether. After filtration, the ethereal
filtrate was concentrated and subjected to HPLC separation
[Develosil ODS-10 (20ꢀ250 mm), 57:26:17 MeOH–
MeCN–water, 8 mL/min, detected at 254 nm] to afford 12
(0.6 mg, tR¼26 min, 31% from 10), 13 (1.2 mg, tR¼28 min,
56% from 10), and the fraction containing 11 (1.5 mg,
tR¼39 min), which was further purified by HPLC [Develosil
ODS-10 (20ꢀ250 mm), 75:25 MeCN–water, 8 mL/min, de-
tected at 254 nm] to give 11 (0.7 mg, tR¼43 min, 26% from
10) and 14-epi-113b (0.5 mg, tR¼46 min, 19% from 10).
C21–C34 fragment 13: colorless powder, [a]1D5 ꢁ31.5 (c
0.40, CHCl3); UV (MeOH) lmax 244 nm (3 19,000); IR
(CHCl3) 3410, 1730, 1590, 1515, 1250, 1075, 1075,
960 cmꢁ1 1H NMR (CDCl3, 500 MHz) d 0.88 (3H, d,
;
J¼6.7 Hz, 26-Me), 0.95 (1H, m, H27), 0.95 (3H, d,
J¼6.7 Hz, 24-Me), 1.08 (3H, d, J¼7.0 Hz, 30-Me), 1.09
(3H, d, J¼7.0 Hz, 32-Me), 1.31 (1H, m, H28), 1.36 (1H,
m, H30), 1.40 (1H, m, H28), 1.48 (1H, ddd, J¼13.4, 4.9,
3.5 Hz, H33), 1.52 (1H, m, H27), 1.78 (1H, dddq, J¼10.0,
3.3, 3.1, 6.7 Hz, H26), 1.88 (1H, dddd, J¼14.2, 7.6, 6.4,
5.4 Hz, H22), 1.99 (1H, m, H24), 2.00 (1H, m, H22), 2.02
(6H, s, Ac), 2.20 (1H, m, H32), 2.29 (1H, dd, J¼13.4,
8.6 Hz, H33), 3.76 (1H, ddd, J¼8.2, 4.6, 3.6 Hz, H29),
3.80 (1H, d, J¼1.2 Hz, H31), 4.10 (1H, dt, J¼11.0,
7.0 Hz, H21), 4.21 (1H, dt, J¼11.0, 6.4 Hz, H21), 4.79
(1H, dd, J¼9.5, 3.1 Hz, H25), 5.10 (1H, ddd, J¼7.8, 5.4,
2.3 Hz, H23), 5.41 (1H, d, J¼4.9 Hz, H34), 6.78 (1H, br s,
NH), 7.29 (2H, d, J¼8.9 Hz, ArH), 7.41 (2H, d, J¼8.9 Hz,
ArH); HRMS (FAB) found m/z 612.2167, calcd for
C22H2779Br2N2O5 (M+H)+ 612.2172.
4.3.7. Acetonides 14 and 15. A mixture of 11 (1.2 mg,
0.0016 mmol) and K2CO3 (4 mg, 0.029 mmol) in MeOH
(0.8 mL) was stirred at room temperature for 23 h. The reac-
tion mixture was poured into saturated ammonium chloride
(2 mL), and the mixture was extracted with four 2-mL por-
tions of EtOAc. The combined organic layers were concen-
trated. To a cooled solution of the residue in a mixture of
acetone (0.3 mL) and 2,2-dimethoxypropane (0.6 mL) at
0 ꢂC was added (+)-10-camphorsulfonic acid (0.6 mg,
0.0026 mmol), and the mixture was stirred at 0 ꢂC for 1 h.
The reaction mixture was diluted with saturated NaHCO3
(3 mL) and extracted with three 3-mL portions of 1:1 hex-
ane–EtOAc. After concentration of the combined organic
layers, the residual oil was chromatographed on silica gel
(1 g) eluted with 5:1 benzene–EtOAc to give 14 (0.9 mg,
79%): colorless powder, [a]2D3 +5 (c 0.06, CHCl3); IR
C5–C14 fragment 11: colorless powder, [a]1D7 +26 (c 0.10,
CHCl3); UV (MeOH) lmax 244 nm (3 44,000); IR (CHCl3)
1
3690, 3430, 3340 (br), 1730, 1595, 1520, 1250 cmꢁ1; H
NMR (CDCl3, 500 MHz) d 0.89 (3H, d, J¼7.0 Hz, 10-
Me), 0.95 (3H, d, J¼7.0 Hz, 8-Me), 1.13 (1H, m, H11),
1.26 (3H, d, J¼6.7 Hz, 14-Me), 1.40 (1H, m, H12), 1.61
(1H, m, H12), 1.63 (1H, m, H11), 1.73 (1H, m, H10), 1.88
(1H, m, H6), 2.00 (1H, m, H6), 2.03 (3H, s, Ac), 2.06 (3H,
s, Ac), 2.07 (1H, m, H8), 3.17 (1H, m, H13), 3.41 (3H, s,
(CHCl3) 3430, 1730, 1590, 1520, 1400, 1310, 1080 cmꢁ1
;
1H NMR (270 MHz, CDCl3) d 0.82 (3H, d, J¼6.4 Hz),
0.87 (3H, d, J¼6.7 Hz), 1.07 (1H, m), 1.26 (3H, d,