730
Vol. 52, No. 6
acid and extracted with ethyl acetate. The organic layer was washed with
brine, dried over anhydrous magnesium sulfate, and concentrated under re-
duced pressure. The crude product was purified by silica gel column chro-
matography (AcOEt/hexaneꢂ1/9 to 2/1) to afford 10 (228 mg, quant.) as a
colorless oil. 1H-NMR (CDCl3) d: 3.60 (td, Jꢂ5.1, 7.7 Hz, 2H), 3.60 (s, 6H),
3.62 (s, 6H), 4.04 (td, Jꢂ5.1, 7.7 Hz, 2H), 4.45 (d, Jꢂ11.1 Hz, 2H), 4.50 (d,
Jꢂ11.1 Hz, 2H), 4.66 (d, Jꢂ10.5 Hz, 2H), 4.73 (d, Jꢂ10.5 Hz, 2H), 5.54 (s,
2H), 6.71 (d, Jꢂ8.4 Hz, 4H), 6.72 (d, Jꢂ8.4 Hz, 4H), 7.13 (d, Jꢂ8.4 Hz,
4H), 7.15 (d, Jꢂ8.4 Hz, 4H). 13C-NMR (CDCl3) d: 54.92 (4C), 71.82 (2C),
74.92 (2C), 79.65 (2C), 83.22 (2C), 113.46 (4C), 113.53 (4C), 127.45 (2C),
129.16 (4C), 129.30 (4C), 130.25 (2C), 130.77 (2C), 158.88 (2C), 158.96
(2C). Anal. Calcd for C38H42O8: C, 72.82; H, 6.75. Found: C, 72.54; H, 6.79.
IR (neat) cmꢃ1: 3000, 2950, 2400, 1610, 1580, 1510, 1460, 1300. [a]D
ꢀ65.9 (cꢂ1.04, CHCl3).
1440, 1240. [a]D ꢀ18.7 (cꢂ1.03, CHCl3).
(3S,4R,5R,6S)-3-(2ꢁ-Methoxybenzyloxy)-5-(4ꢁ-methoxybenzyloxy)-4,6-
dihydro-octa-1,7-diene 7b Methyltriphenylphosphonium bromide (5.59 g,
15.7 mmol) was suspended in ether (20 ml). Then the reaction mixture was
treated with n-butyllithium (8.20 ml, 12.8 mmol) and stirred at room temper-
ature for 1.5 h. A solution of 6b (1.09 g, 2.16 mol) in tetrahydrofuran (20 ml)
was added to the reaction mixture, and stirred at the same temperature
overnight. The reaction mixture was diluted with water and extracted with
ethyl acetate. The organic layer was washed with brine, dried over anhy-
drous magnesium sulfate, and concentrated under reduced pressure. The
crude product was purified by silica gel column chromatography
(AcOEt/hexaneꢂ1/4 to 1/2) to afford 7b (810 mg, 75%) as a colorless oil.
1H-NMR (CDCl3) d: 2.8—3.3 (br, 2H), 3.45 (dd, Jꢂ3.5, 4.8 Hz, 1H), 3.72
(dd, Jꢂ3.5, 6.8 Hz, 1H), 3.77 (s, 3H), 3.80 (s, 3H), 4.02 (dd, Jꢂ6.8, 7.6 Hz,
1H), 4.36 (tdd, Jꢂ1.5, 4.8, 5.8 Hz, 1H), 4.45 (d, Jꢂ11.1 Hz, 1H), 4.51 (d,
Jꢂ11.1 Hz, 1H), 4.61 (d, Jꢂ11.1 Hz, 1H), 4.65 (d, Jꢂ11.1 Hz, 1H), 5.19 (td,
Jꢂ1.5, 10.6 Hz, 1H), 5.31—5.40 (m, 3H), 5.78 (ddd, Jꢂ7.6, 10.8, 16.9 Hz,
1H), 5.92 (ddd, Jꢂ5.8, 10.6, 17.2 Hz, 1H), 6.83—6.96 (m, 4H), 7.20—7.33
(m, 4H). 13C-NMR (CDCl3) d: 55.08, 55.10, 66.56, 73.11, 73.84, 74.06,
80.39, 80.83, 110.26 (2C), 113.63 (2C), 116.06, 119.59, 120.26, 125.75,
129.18, 129.40 (2C), 129.61, 129.78, 130.22, 134.59, 137.85, 157.43,
159.11. HR-FAB-MS (NBAꢀNaCl) m/z: Calcd C24H30O6Na (MꢀNa)ꢀ
437.1940, Found 437.1942. IR (neat) cmꢃ1: 3470, 2900, 1610, 1580, 1515,
1490, 1460, 1440, 1240. [a]D ꢀ8.93 (cꢂ1.04, CHCl3).
3,4,5,6-O-Tetra-(4ꢁ-methoxybenzyl)-D-myo-inositol 11 To an ice-
cooled solution of 10 (470 mg, 0.72 mmol) in methylene chloride (15 ml)
was added quinuclidine (4.2 mg, 0.036 mmol, 5 mol%), 4-methylmorpholine
N-oxide (252 mg, 2.15 mmol) and 2% osmium tetroxide in water (0.46 ml,
0.036 mmol, 5 mol%). The reaction mixture was stirred at room temperature
for 4 d, diluted with water and extracted with ethyl acetate. The organic layer
was washed with brine, dried over anhydrous magnesium sulfate, and con-
centrated under reduced pressure. The crude product was purified by silica
gel column chromatography (AcOEt/hexaneꢂ1/4 to 2/1) to afford 11
1
(379 mg, 80%) as a colorless solid. mp 120—121 °C. H-NMR (CDCl3) d:
2.44 (br, 2H), 3.39—3.45 (m, 3H), 3.78 (s, 3H), 3.78 (t, Jꢂ9.5 Hz, 1H), 3.80
(s, 3H), 3.91 (t, Jꢂ9.5 Hz, 1H), 4.13 (t, Jꢂ2.4 Hz, 1H), 4.59—4.89 (m, 8H),
6.85 (d, Jꢂ8.4 Hz, 4H), 7.23—7.27 (m, 4H). 13C-NMR (CDCl3) d: 55.21
(2C), 55.23 (2C), 69.09, 71.63, 72.34, 75.18, 75.32, 75.55, 79.70, 80.89,
81.41, 82.98, 113.73 (2C), 113.76 (2C), 113.84 (2C), 113.94 (2C), 129.38
(2C), 129.48 (2C), 129.52 (2C), 129.57 (2C), 129.87, 130.63, 130.74,
130.87, 159.10 (2C), 159.28, 159.32. Anal. Calcd for C38H42O8: C, 69.07; H,
6.71. Found: C, 68.94; H, 6.69. IR (KBr) cmꢃ1: 3400, 2900, 1610, 1580,
1520, 1460, 1350, 1300. [a]D ꢃ22.6 (cꢂ1.04, CHCl3).
(ꢀ)-3,5-O-Di-(4ꢁ-methoxybenzyl)-conduritol B 8a To a solution of 7a
(50.0 mg, 0.12 mmol) in methylene chloride (10 ml) was added benzylidene-
bis(tricyclohexylphosphine)-dicholororuthenium (1st Grubbs catalyst)
(9.9 mg, 0.012 mmol, 10 mol%). The reaction mixture was stirred at room
temperature for 3 h and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography (AcOEt/
hexaneꢂ1/1) to afford 8a (40.5 mg, 87%) as a colorless solid. mp 130—
131 °C. 1H-NMR (CDCl3) d: 3.39 (dd, Jꢂ7.9, 10.3 Hz, 1H), 3.80 (s, 6H),
3.80 (dd, Jꢂ7.9, 10.3 Hz, 1H), 4.08 (tdd, Jꢂ1.8, 3.2, 7.9 Hz, 1H), 4.29 (td,
Jꢂ1.8, 7.9 Hz, 1H), 4.64 (d, Jꢂ11.4 Hz, 1H), 4.68 (d, Jꢂ11.4 Hz, 1H), 4.77
(d, Jꢂ11.4 Hz, 1H), 4.83 (d, Jꢂ11.4 Hz, 1H), 5.61 (td, Jꢂ1.8, 10.3 Hz, 1H),
5.68 (td, Jꢂ1.8, 10.3 Hz, 1H), 6.86—6.93 (m, 4H), 7.27—7.34 (m, 4H). 13C-
NMR (CDCl3) d: 55.28 (2C), 71.82, 72.82, 74.71, 75.01, 79.43, 84.13,
113.89 (2C), 114.12 (2C), 127.32 (2C), 129.47 (2C), 129.67 (2C), 130.38,
130.47, 159.30, 159.50. IR (KBr) cmꢃ1: 1610, 1510, 1460, 1300, 1250. HR-
FAB-MS (NBAꢀNaCl) m/z: Calcd C22H26O6Na (MꢀNa)ꢀ 409.1627, Found
409.1613. [a]D: ꢀ96.2° (cꢂ0.52, CHCl3).
(ꢀ)-3-O-(2ꢁ-Methoxybenzyl)-5-O-(4ꢁ-methoxybenzyl)-conduritol B 8b
To a solution of 7b (3.43 g, 8.28 mmol) in methylene chloride (140 ml) was
added benzylidene-bis(tricyclohexylphosphine)-dicholororuthenium (1st
Grubbs catalyst) (681 mg, 0.83 mmol, 10 mol%) and stirred at room temper-
ature for 3 h. The reaction mixture was concentrated under reduced pressure.
The crude product was purified by silica gel column chromatography
(AcOEt/hexaneꢂ1/1) to afford 8a (2.69 m, 84%) as a colorless solid. mp
134—135 °C. 1H-NMR (CDCl3) d: 2.25 (br, 1H), 3.05 (br, 1H), 3.43 (dd,
Jꢂ7.8, 10.3 Hz, 1H), 3.81 (s, 3H), 3.84 (s, 3H), 3.84 (dd, Jꢂ7.8, 10.3 Hz,
1H), 4.09—4.15 (m, 1H), 4.26—4.31 (m, 1H), 4.72 (s, 2H), 4.74 (d,
Jꢂ11.4 Hz, 1H), 4.88 (d, Jꢂ11.4 Hz, 1H), 5.62 (td, Jꢂ2.0, 10.3 Hz, 1H),
5.75 (td, Jꢂ2.0, 10.3 Hz, 1H), 6.88—6.98 (m, 4H), 7.26—7.39 (m, 4H). 13C-
NMR (CDCl3) d: 55.19, 55.35, 67.52, 72.06, 74.42, 74.80, 80.58, 83.78,
110.32, 113.97 (2C), 120.51, 126.32, 127.17, 129.10, 129.29, 129.57,
129.63 (2C), 130.60, 157.23, 159.31. Anal. Calcd for C22H26O6: C, 68.38; H,
6.78. Found: C, 68.13; H, 6.70. IR (KBr) cmꢃ1: 3350, 2900, 1610, 1580,
1510, 1490, 1460, 1390, 1360. [a]D ꢀ125 (cꢂ1.03, CHCl3).
(ꢀ)-Conduritol B 9 To a solution of 8a (100 mg, 0.26 mmol) in MeOH
(5 ml) was added water (5 ml) and Dowex-50xw8TM(Hꢀ). Then, the reaction
mixture was refluxed for 5 h. The reaction mixture was filtered and concen-
trated under reduced pressure. The crude product was dissolved in the water,
and washed with CHCl3. The aqueous layer was lyophilized to afford 9
(33.6 mg, 90%) as a colorless solid. mp 172—173 °C. 1H-NMR (CD3OD) d:
3.36 (d, Jꢂ7.5 Hz, 2H), 4.19 (d, Jꢂ7.5 Hz, 2H), 5.53 (s, 2H). 13C-NMR
(CD3OD) d: 77.63 (2C), 77.43 (2C), 130.70 (2C). [a]D ꢀ183 (cꢂ1.1,
CH3OH).
(ꢀ)-3,4,5,6-O-Tetra-(4ꢁ-methoxybenzyl)-conduritol B 10 A solution
of 8a (138 mg, 0.35 mmol) in N,N-dimethylformamide (5 ml) was cooled in
an ice bath and slowly mixed with 60% sodium hydride (49.9 mg,
1.25 mmol). The reaction mixture was stirred at the same temperature for
2 h. Then, 4-methoxybenzyl chloride (0.15 ml, 1.07 mmol) was added drop-
wise while cooling in an ice bath. The reaction mixture was stirred at room
temperature overnight, poured onto ice, diluted with aqueous hydrochloric
1,2-O-Dibenzyl-3,4,5,6-O-tetra-(4ꢁ-methoxybenzyl)-D-myo-inositol 12
A solution of 11 (379 mg, 0.57 mmol) in N,N-dimethylformamide (5 ml) was
cooled in an ice bath and slowly mixed with 60% sodium hydride (73.4 mg,
1.84 mmol). The reaction mixture was stirred at the same temperature for
2 h. Then, benzyl bromide (0.18 ml, 1.55 mmol) was added dropwise while
cooling in an ice bath. The reaction mixture was stirred at room temperature
overnight, poured onto ice, diluted with aqueous hydrochloric acid and ex-
tracted with ethyl acetate. The organic layer was washed with brine, dried
over anhydrous magnesium sulfate, and concentrated under reduced pres-
sure. The crude product was purified by silica gel column chromatography
(AcOEt/hexaneꢂ1/4) to afford 12 (446 mg, 93%) as a colorless solid. mp
90—91 °C. 1H-NMR (CDCl3) d: 3.30 (dd, Jꢂ2.4, 9.9 Hz, 1H), 3.34 (dd,
Jꢂ2.4, 9.9 Hz, 1H), 3.42 (t, Jꢂ9.2 Hz, 1H), 3.78 (s, 3H), 3.79 (s, 3H), 3.80
(s, 3H), 3.82 (s, 3H), 3.99 (m, 1H), 4.03 (dd, Jꢂ9.2, 9.9 Hz, 1H), 4.04 (dd,
Jꢂ9.2, 9.9 Hz, 1H), 4.51 (d, Jꢂ11.4 Hz, 1H), 4.58 (d, Jꢂ11.4 Hz, 1H), 4.59
(d, Jꢂ11.4 Hz, 1H), 4.65 (d, Jꢂ11.4 Hz, 1H), 4.73—4.86 (m, 8H), 6.79—
6.87 (m, 8H), 7.20—7.42 (m, 18H). 13C-NMR (CDCl3) d: 55.23 (2C), 55.25
(2C), 72.42, 72.73, 74.03, 74.40, 75.46, 75.49, 75.53, 80.72, 80.97, 81.44
(2C), 83.49, 113.68 (4C), 113.73 (4C), 127.26, 127.48 (2C), 127.53, 127.72
(2C), 128.09 (2C), 128.34 (2C), 129.14 (2C), 129.32 (2C), 129.67 (2C),
129.69 (2C), 130.53, 131.07, 131.12, 131.16, 138.47, 139.01, 159.02,
159.06 (2C), 159.10. Anal. Calcd for C52H56O10: C, 74.26; H, 6.71. Found:
C, 74.03; H, 6.69. IR (KBr) cmꢃ1: 2900, 1610, 1580, 1510, 1450, 1350,
1300, 1250. [a]D ꢀ0.80 (cꢂ1.03, CHCl3).
1,2-O-Dibenzyl-D-myo-inositol (ꢂ)-13 To a solution of 12 (161 mg,
0.19 mmol) in methylene chloride (3 ml) was added water (0.3 ml) and 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (261 mg, 1.15 mmol). The reaction
mixture was stirred at room temperature for 2 h, diluted with water and
methanol and filtered by Dowex-1X4-50TM(OHꢃ). The filtrate was concen-
trated under reduced pressure and purified by silica gel column chromatog-
raphy (MeOH/CHCl3ꢂ1/3) to afford (ꢃ)-13 (46.8 mg, 68%) as a colorless
solid. mp 200—201 °C. 1H-NMR (CDCl3) d: 3.08 (t, Jꢂ9.3 Hz, 1H), 3.19—
3.20 (m, 1H), 3.28 (dd, Jꢂ2.7, 9.9 Hz, 1H), 3.56 (t, Jꢂ9.3 Hz, 1H), 3.73 (t,
Jꢂ9.3 Hz, 1H), 3.93 (t, Jꢂ2.7 Hz, 1H), 4.53 (d, Jꢂ12.3 Hz, 1H), 4.58 (d,
Jꢂ12.3 Hz, 1H), 4.68 (d, Jꢂ12.3 Hz, 1H), 4.73 (d, Jꢂ12.3 Hz, 1H), 7.14—
7.30 (m, 10H). 13C-NMR (CDCl3) d: 73.58, 73.77, 74.19, 74.62, 75.84,
76.80, 79.12, 81.94, 128.32, 128.62, 128.88 (2C), 129.01 (2C), 129.08 (2C),
129.32 (2C), 139.98, 140.57. HR-FAB-MS (NBAꢀNaCl) m/z: Calcd
C20H24O6Na (MꢀNa)ꢀ 383.1471, Found 383.1482. IR (KBr) cmꢃ1: 3400,
30250, 2920, 2500, 1490, 1410, 1370. [a]D ꢃ39.5 (cꢂ0.26, MeOH).
1,2-O-Dibenzyl-D-myo-inositol 3,4,5,6-tetrakisphoric acid dibenzyl