H. Takamura et al. / Tetrahedron 66 (2010) 5329e5344
5339
6H), 0.03 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
145.6, 137.9, 137.2
(s, 3H), 1.19 (s, 9H), 1.15 (s, 3H), 1.13 (s, 3H), 1.09 (s, 9H), 1.05 (d,
(2C), 135.5 (4C), 134.5, 134.1 (2C), 132.4, 129.4 (2C), 128.2 (2C), 127.5
(4C), 114.4, 114.1, 87.3, 82.7, 82.2, 77.6, 77.5, 77.2, 76.2, 75.2, 72.7,
72.5, 71.4, 70.8, 66.6, 64.0 (2C), 49.5, 35.0, 34.9, 34.4, 32.5, 29.3, 29.1,
28.2, 27.5, 26.9 (3C), 26.1 (3C), 26.0 (3C), 23.3, 20.9, 20.2, 19.3, 18.3,
18.2, 15.5, 12.4, ꢁ1.9 (2C), ꢁ3.9, ꢁ5.0; HRMS (ESI TOF) calcd for
C67H103Cl3O9Si3Na (MþNa)þ 1265.5868, found 1265.6018.
J¼7.1 Hz, 3H), 0.94 (s, 9H), 0.20 (s, 3H), 0.17 (s, 3H), 0.07 (s, 3H), 0.06
(s, 3H); 13C NMR (100 MHz, CDCl3)
d 138.6, 135.5 (4C), 134.1 (2C),
129.4 (2C), 128.2 (2C), 127.6 (2C), 127.5 (4C), 127.4, 88.2, 86.6, 85.0,
82.2, 77.6, 77.2, 76.1, 75.5, 73.1, 72.9, 72.8, 72.6, 70.8, 70.7, 64.0, 49.5,
37.8, 37.7, 35.0, 33.9, 32.6, 29.6, 29.5, 29.3, 29.1, 28.9, 27.3, 27.0 (3C),
26.0 (3C), 25.8 (3C), 24.0, 20.9, 19.3, 18.3, 18.1, 16.2, 12.4, ꢁ2.0, ꢁ2.2,
ꢁ4.2, ꢁ4.8; (100 MHz, C6D6)
d 139.5, 136.0 (4C), 134.5 (2C), 129.9
4.16. Pentacycle 30
(2C), 128.5(2C), 127.9 (4C), 127.5 (3C), 88.7, 86.6, 85.0, 83.0, 78.1,
77.7, 76.6, 76.2, 73.8, 73.4, 73.3, 73.1, 71.2, 71.0, 64.4, 50.0, 38.1 (2C),
35.6, 34.8, 33.3, 30.3, 30.0, 29.6, 29.5, 27.9 (2C), 27.3 (3C), 26.5 (3C),
26.2 (3C), 24.1, 21.4, 19.6, 18.7, 18.5, 16.1, 13.0, ꢁ1.8, ꢁ1.9, ꢁ3.8, ꢁ4.6;
HRMS (ESI TOF) calcd for C65H104O9Si3Na (MþNa)þ 1135.6886,
found 1135.6899.
To a solution of 28 (10.9 mg, 8.77
added the Grubbs’ catalyst 29 (22 mg, 26
was stirred at 100 ꢀC. After 15 min, an additional amount of 29
(3.6 mg, 4.37
mol) was added. After stirring for 15 min at 100 ꢀC,
mmol) in toluene (2.9 mL) was
mmol), and the mixture
m
the reaction was quenched with Et3N at room temperature, diluted
with EtOAc, filtered through a short silica gel column (EtOAc).
Concentration and chromatography (cH2Cl2/EtOAc, 1:0 to 100:1 to
4.18. Alcohol 2
50:1, hexane/EtOAc, 40:1 to 30:1 to 20:1) gave 30 (7.4 mg, 69%):
A mixture of 32 (5.6 mg, 5.03 mmol) and Pd(OH)2eC (7.2 mg) in
24
colorless oil; Rf¼0.46 (hexane/EtOAc, 7:1); [
CHCl3); IR (neat) 2929, 1090 cmꢁ1
7.67e7.61 (m, 4H), 7.42e7.31 (m, 6H), 7.31 (s, 2H), 5.63 (dd, J¼13.3,
a
]
ꢁ11.0 (c 0.67,
EtOAc (1.2 mL) was stirred under H2 atmosphere at room temper-
ature. After 45 min, the catalyst was filtered off through a short
silica gel column (EtOAc) and concentrated. The residue was puri-
fied by chromatography (hexane/EtOAc, 10:1 to 7:1 to 4:1) to give 2
D
;
1H NMR (400 MHz, CDCl3)
d
2.3 Hz, 1H), 5.41 (dd, J¼13.3, 1.5 Hz, 1H), 4.67 (s, 2H), 4.16 (dd,
J¼11.3, 4.8 Hz, 1H), 3.95 (br s, 1H), 3.89 (br d, J¼9.3 Hz, 1H),
3.75e3.46 (m, 5H), 3.39 (dd, J¼6.1, 6.1 Hz, 1H), 3.31 (d, J¼10.7 Hz,
1H), 3.28e3.18 (m, 3H), 2.06 (ddd, J¼11.5, 4.3, 4.3, 1H), 2.03e1.95
(m, 1H), 1.94e1.21 (m, 17H), 1.17 (s, 3H), 1.14 (s, 3H), 1.11 (s, 3H), 1.02
(s, 9H), 0.89 (s, 9H), 0.88 (d, J¼6.6 Hz, 3H), 0.81 (s, 9H), 0.07 (s, 6H),
(4.6 mg, 89%): colorless oil; Rf¼0.20 (hexane/EtOAc, 4:1); [
a]
22 ꢁ9.1
D
(c 0.87, CHCl3); IR (neat) 3606e3144, 2928, 1731, 1085 cmꢁ1
;
1H
NMR (400 MHz, CDCl3) d 7.66e7.61 (m, 4H), 7.41e7.31 (m, 6H), 4.17
(dd, J¼11.6, 5.0 Hz, 1H), 3.94 (dd, J¼3.7, 3.7 Hz, 1H), 3.73e3.56 (m,
5H), 3.41e3.22 (m, 3H), 3.22e3.16 (m, 2H), 3.10 (dd, J¼12.1, 3.7 Hz,
1H), 2.17e1.20 (m, 23H), 1.14 (s, 3H), 1.12 (s, 3H), 1.08 (s, 3H), 1.02 (s,
9H), 0.89 (s, 9H), 0.88 (d, J¼6.3 Hz, 3H), 0.81 (s, 9H), 0.06 (s, 3H),
0.04 (s, 3H), 0.03 (s, 3H), 0.03 (s, 3H); 13C NMR (100 MHz, CDCl3)
0.04 (s, 3H), 0.03 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 138.8, 137.2
(2C), 135.5 (4C), 134.5, 134.1 (2C), 132.4, 129.9, 129.4 (2C), 128.2 (2C),
127.5 (4C), 88.2, 86.3, 83.9, 80.2, 78.3, 77.6, 77.2, 76.0, 75.7, 73.1,
72.6, 71.2, 70.8, 66.6, 64.0, 49.5, 38.1, 35.0, 33.7, 32.6, 30.4, 29.3, 29.1,
27.2, 26.9 (3C), 26.7, 26.0 (3C), 25.8 (3C), 21.9, 20.9, 19.3, 18.3, 18.2,
17.7, 12.3, ꢁ1.9, ꢁ2.1, ꢁ4.1, ꢁ4.9; HRMS (ESI TOF) calcd for
C65H99Cl3O9Si3Na (MþNa)þ 1237.5554, found 1237.5496.
d
135.5 (4C), 134.1 (2C), 129.4 (2C), 127.5 (4C), 88.3, 86.5, 84.8, 82.3,
77.6, 77.2, 76.0, 75.5, 73.1, 72.9, 72.5, 70.8, 64.0, 63.0, 49.5, 37.7, 37.5,
35.0, 33.9, 32.5, 30.3, 29.8, 29.6, 29.3, 28.8, 26.9 (3C), 26.5, 26.0 (3C),
25.8 (3C), 24.0, 20.9,19.3,18.3,18.1,16.1,12.4, ꢁ2.0, ꢁ2.2, ꢁ4.2, ꢁ4.8;
HRMS (ESI TOF) calcd for C58H98O9Si3Na (MþNa)þ 1045.6416,
found 1045.6412.
4.17. Benzyl ether 32
A mixture of 30 (5.7 mg, 4.69
mmol) and PdeC (5.6 mg) and Et3N
4.19. TBS ether 36
(50 L) in EtOH (1 mL) was stirred under H2 atmosphere. After
m
1.5 h, the catalyst was filtered off through a short silica gel column
(EtOAc), and the filtrate was concentrated to give the crude benzyl
ether 31, which was used for the next reaction directly.
To a stirred solution of 18 (215 mg, 0.257 mmol) in CH2Cl2
(7.0 mL) were added HMDS (0.86 mL, 5.14 mmol) and TMSI
(0.36 mL, 2.53 mmol) at 0 ꢀC. After 30 min, the reaction mixture was
quenched with saturated NaHCO3, and diluted with Et2O. The or-
ganic layer was washed with water and brine. After concentration,
the residue was dissolved in MeOH (4.0 mL) and CH2Cl2 (4.0 mL). To
this solution at 0 ꢀC was added CSA (26 mg, 0.112 mmol), and the
mixture was stirred for 40 min at the same temperature. The re-
action mixture was quenched with Et3N, diluted with EtOAc, then
washed with water and brine. Concentration gave the crude alcohol,
which was used for the next reaction directly.
To a stirred solution of the crude benzyl ether, pyridine (85
1.06 mmol) and KO2CN]NCO2K (68.3 mg, 0.352 mmol) in MeOH
(1 mL) at room temperature was added a solution of AcOH (40 L,
mL,
m
0.704 mmol) in MeOH (0.3 mL) over 75 min via a syringe pomp. The
reaction mixture was the quenched with saturated NH4Cl, diluted
with Et2O. The organic layer was washed with saturated CuSO4,
water, saturated NaHCO3, and brine. After concentration, the resi-
due was subjected to the same procedure described above to
complete the reaction. The crude product obtained was purified by
chromatography (hexane/EtOAc, 40:1 to 20:1 to 15:1) to give 32
(4.4 mg, 84% for the 2 steps): colorless oil; Rf¼0.39 (hexane/EtOAc,
To a stirred solution of the alcohol in CH2Cl2 (5.0 mL) at 0 ꢀC
were added 2,6-lutidine (0.15 mL, 1.28 mmol) and TBSOTf (0.14 mL,
0.789 mmol). After stirring for 1 h at room temperature, the re-
action mixture was cooled to 0 ꢀC, and quenched with MeOH. The
mixture was diluted with Et2O, and washed with water and brine.
Concentration and chromatography (hexane/EtOAc, 50:1 to 30:1)
7:1); [
(400 MHz, CDCl3)
a
]
24 ꢁ13.1 (c 0.21, CHCl3); IR (neat) 2929, 1090 cmꢁ1; 1H NMR
D
d
7.64 (dd, J¼7.8, 1.5 Hz, 4H), 7.41e7.20 (m, 11H),
4.49 (s, 2H), 4.17 (dd, J¼11.5, 5.1 Hz, 1H), 3.94 (dd, J¼3.7, 3.7 Hz, 1H),
3.73e3.56 (m, 3H), 3.51e3.43 (m, 2H), 3.42e3.36 (m,1H), 3.34e3.15
(m, 4H), 3.10 (dd, J¼12.2, 3.9 Hz, 1H), 2.13e1.20 (m, 23H), 1.14 (s,
3H), 1.10 (s, 3H), 1.06 (s, 3H), 1.02 (s, 9H), 0.89 (s, 9H), 0.88 (d,
J¼6.3 Hz, 3H), 0.81 (s, 9H), 0.05 (s, 3H), 0.03 (s, 6H), 0.03 (s, 3H);
gave 36 (218 mg, 93% for the 2 steps): colorless oil; Rf¼0.70 (hex-
27
ane/EtOAc, 4:1); [
a
]
ꢁ10.2 (c 0.95, CHCl3); IR (neat) 3434, 3069,
D
1079 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.64 (dd, J¼7.8, 1.7 Hz, 4H),
7.42e7.31 (m, 6H), 7.31e7.19 (m, 10H), 4.56 (d, J¼12.0 Hz, 1H), 4.48
(s, 2H), 4.36 (d, J¼12.0 Hz, 1H), 4.25 (dd, J¼11.3, 5.0 Hz, 1H),
4.04e3.97 (m, 1H), 3.73e3.57 (m, 2H), 3.48 (d, J¼7.1 Hz, 1H),
3.47e3.35 (m, 3H), 3.44 (d, J¼7.1 Hz,1H), 3.25 (d, J¼9.5 Hz,1H), 2.34
(ddd, J¼12.2, 4.1, 4.1 Hz, 1H), 2.01 (dd, J¼14.8, 3.6 Hz, 1H), 1.90 (dd,
J¼15.6, 3.9 Hz, 1H), 1.74e1.44 (m, 5H), 1.38e1.22 (m, 3H), 1.16 (s,
3H), 1.15 (s, 3H), 1.03 (s, 9H), 0.90e0.84 (m, 12H), 0.06 (s, 3H), 0.03
(400 MHz, C6D6)
d
7.83e7.73 (m, 4H), 7.33 (d, J¼7.6 Hz, 2H),
7.26e7.06 (m, 9H), 4.42 (dd, J¼11.4, 5.7 Hz, 1H), 4.36 (s, 2H), 4.03 (br
s, 1H), 3.92 (ddd, J¼11.7, 9.3, 4.9 Hz, 1H), 3.78e3.60 (m, 2H),
3.59e3.27 (m, 6H), 3.23 (ddd, J¼8.9, 8.9, 3.7 Hz, 1H), 3.17 (dd,
J¼12.0, 4.0 Hz, 1H), 2.34 (ddd, J¼12.0, 4.0, 4.0 Hz, 1H), 2.25e2.15 (m,
2H), 2.10e1.65 (m, 13H), 1.65e1.42 (m, 5H), 1.40e1.25 (m, 2H), 1.24