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(3H, m), 4.82 (1H, d, J = 12.1 Hz) 5.16 (1H, d, J = 11.8 Hz), 5.32 (1H,
dd, J = 17.2, 1.5 Hz), 5.89–6.00 (1H, m), 6.86 (2H, d, J = 8.6 Hz),
7.26–7.38 (7H, m). 13C NMR (CDCl3) d: 26.9, 27.0, 55.2, 69.8, 71.5,
72.4, 72.9, 75.9, 77.1, 78.0, 79.0, 80.6, 11.6, 113.8, 116.5, 127.7,
127.9, 128.3, 129.6, 129.9, 135.1, 138.0, 159.4. IR (KBr) 3450,
2930, 1610, 1070, 790 cmꢀ1. HRMS(FAB) m/z calcd for C27H34O7Na
(M+Na)+ 493.2202. Found: 493.2216.
4.8. DL-2,6-Di-O-acetyl-1-O-(p-methoxybenzyl)-4,5-O-
isopropylidene-myo-inositol (8)
To a solution of 7 (0.38 g, 0.74 mmol) in MeOH (25 ml) was
added W-2 Raney Nickel (Ni) (0.20 g) and the resulting mixture
was stirred at 50 °C under hydrogen for 3 h. The mixture was fil-
tered through a pad of celite and concentrated under reduced pres-
sure. The residue was purified by silica gel column
chromatography (hexane/AcOEt = 1:1) to afford 8 (0.20 g, 64%) as
a colorless oil.
4.6. DL-3-O-Benzyl-1-O-(p-methoxybenzyl)-4,5-O-
isopropylidene-myo-inositol (6)
1H NMR (CDCl3) d: 1.42 (3H, s), 1.46 (3H, s), 2.07 (3H, s), 2.18
(3H, s), 2.51 (1H, br s), 3.41–3.47 (2H, m), 3.80 (3H, s), 3.92 (2H,
d, J = 7.3 Hz), 4.35 (1H, d, J = 11.7 Hz), 4.60 (1H, d, J = 11.7 Hz),
5.36 (1H, dd, J = 10.3, 9.6 Hz), 5.65 (1H, s), 6.87 (2H, d, J = 8.6 Hz),
7.19 (2H, d, J = 8.6 Hz). 13C NMR (CDCl3) d: 20.9, 21.1, 26.7
(–CH3 ꢂ 2, acetal), 55.2, 68.9, 70.1, 71.2, 71.7, 76.3, 76.8, 77.6,
112.4, 113.8, 129.1, 129.6, 159.4, 169.8, 170.8. HRMS(FAB) m/z
calcd for C21H28O9Na (M+Na)+ 447.1631. Found: 447.1624.
To a solution of 5 (0.10 g, 0.21 mmol) in EtOH–benzene–H2O
(7:3:1, 22 ml) was added diazabicyclo[2.2.2]octane (DABCO)
(0.034 g, 0.30 mmol) followed by tris(triphenylphosphine)rho-
dium(I) chloride (0.028 g, 0.030 mmol) and the resulting mixture
was refluxed for 5 h. The mixture was concentrated under re-
duced pressure and the residue was diluted with AcOEt. The or-
ganic phase was washed with H2O and saturated aqueous NaCl,
dried over Na2SO4, and then concentrated under reduced pres-
sure. To a solution of the residue in acetone–H2O (10:1, 5 ml)
was added mercury(II) oxide (0.046 g, 0.21 mmol). To the result-
ing mixture was added dropwise a solution of mercury(II) chlo-
ride (0.057 g, 0.21 mmol) in acetone–H2O (10:1, 5 ml). The
resulting mixture was stirred at room temperature for 5 min.
The mixture was neutralized with aqueous NaOH, filtered
through a pad of celite and concentrated under reduced pressure.
The residue was diluted with saturated aqueous NaCl. The aque-
ous phase was extracted with CH2Cl2 and the organic phase was
dried over Na2SO4, and then concentrated under reduced pres-
sure. The residue was purified by silica gel column chromatogra-
phy (CH2Cl2/MeOH = 15:1) to afford 6 (0.061 g, 68%) as a white
solid.
4.9. DL-2,6-Di-O-acetyl-1-O-(p-methoxybenzyl)-myo-inositol (9)
To a solution of 8 (0.20 g, 0.47 mmol) in CH2Cl2 (10 ml) was
added ethylene glycol (28 ll, 0.50 mmol) followed by p-toluene-
sulfonic acid monohydrate (0.0095 mg, 0.05 mmol). The resulting
mixture was stirred at room temperature for 10 min. The mixture
was neutralized with Et3N (0.10 ml, 0.72 mmol) and concentrated
under reduced pressure. The crude product was purified by silica
gel column chromatography (CH2Cl2/MeOH = 7:1) to afford 9
(0.16 g, 89%) as a white solid.
1H NMR (CDCl3) d: 1.91 (3H, s), 2.02 (3H, s), 3.20–3.27 (3H, m),
3.41–3.57 (3H, m), 3.67 (3H, s), 4.21 (1H, d, J = 11.2 Hz), 4.47 (1H, d,
J = 11.4 Hz), 5.00 (1H, t, J = 9.9 Hz), 5.55 (1H, dd, J = 6.0, 2.9 Hz),
6.77 (2H, d, J = 8.6 Hz, 2H), 7.19 (2H, d, J = 8.6 Hz). 13C NMR (CDCl3)
d: 21.0, 21.1, 55.7, 71.2, 71.8, 72.4, 74.2, 74.4, 75.3, 76.8, 114.7,
130.6, 130.8, 131.3, 172.4. HRMS(FAB) m/z calcd for C18H24O9Na
(M+Na)+ 407.1318. Found: 407.1319.
1H NMR (CDCl3) d: 1.45 (3H, s),1.47 (3H, s), 2.60 (1H, br s), 2.62
(1H, br s), 3.22–3.24 (2H, m), 3.56 (1H, dd, J = 10.1, 2.8 Hz), 3.80
(3H, s), 4.08 (2H, t, J = 9.7 Hz), 4.24 (1H, s), 4.50 (1H, d,
J = 11.4 Hz), 4.66 (1H, d, J = 11.4 Hz), 4.69 (1H, d, J = 12.1 Hz), 4.85
(1H, d, J = 12.1 Hz), 6.89 (2H, d, J = 8.1 Hz), 7.25–7.38 (7H, m). 13C
NMR (CDCl3) d: 27.2, 27.3, 55.7, 69.0, 70.7, 72.1, 72.5, 76.5, 77.6,
78.6, 81.7, 112.5, 114.4, 128.3, 128.4, 128.8, 129.7, 130.1, 138.3,
160.0. IR (KBr) 3570, 2990, 2930, 1070, 790 cmꢀ1. HRMS(FAB)
m/z calcd for C24H35O7 (M+H)+ 431.2070. Found: 431.2048.
4.10. Preparation of bis(2-cyanoethyl) N,N-diisopropyl
aminophosphoramidite
(Diisopropylamino)dichlorophosphine was prepared by the
method of Uhlmann and Engels11 by adding two equivalents of
diisopropylamine to a solution of phosphorus trichloride in dry
ethyl ether at ꢀ78 °C. The crude product was purified by distilla-
tion under reduced pressure and could be stored as a crystalline so-
lid at ꢀ20 °C. Two equivalents of 2-cyanoethanol were reacted
with the purified product in dehydrated CH2Cl2 in the presence
of diisopropylethylamine to afford bis (2-cyanoethyl) N,N-
diisopropylaminophosphoramidite.
4.7. DL-3-O-Benzyl-2,6-di-O-acetyl-1-O-(p-methoxybenzyl)-4,5-
O-isopropylidene-myo-inositol (7)
To a solution of 6 (0.33 g, 0.76 mmol) in pyridine (10 ml) was
added 4-dimethylaminopyridine (DMAP) (0.024 g, 0.20 mmol)
and acetic anhydride (Ac2O) (0.19 ml, 2.0 mmol), and the result-
ing mixture was stirred at room temperature for 12 h. After aze-
otropic removal of pyridine with toluene under reduced pressure,
the residue was diluted with AcOEt. The organic phase was
washed with H2O and saturated aqueous NaCl, dried over Na2SO4,
and then concentrated under reduced pressure. The crude prod-
uct was purified by silica gel column chromatography (hexane/
AcOEt = 2:1) to afford 7 (0.36 g, 91%) as a white solid. 1H NMR
(CDCl3) d: 1.41 (3H, s),1.46 (3H, s), 2.05 (3H, s), 2.16 (3H, s),
3.34–3.40 (2H, m), 3.61 (1H, dd, J = 10.3, 3.1 Hz), 3.80 (3H, s),
4.03 (1H, t, J = 10.9, 9.8 Hz), 4.32 (1H, d, J = 11.7 Hz), 4.59–4.74
(3H, m), 5.38 (1H, dd, J = 10.3, 9.9 Hz), 5.83 (1H, dd, J = 3.3,
3.2 Hz), 6.87 (2H, d, J = 8.6 Hz), 7.16–7.19 (2H, d, J = 8.6 Hz),
7.26–7.38 (5H, m). 13C NMR (CDCl3) d: 21.0, 21.1, 26.8, 26.8,
55.2, 67.5, 71.2, 71.2, 71.6, 74.6, 76.6, 76.9, 77.0, 112.2, 113.8,
127.7 (2,6-CH, methoxyphenyl and 2,6-CH, phenyl), 128.4,
129.2, 129.5, 137.5, 159.4, 169.8, 170.3. IR (KBr) 2990, 1740,
1100, 740 cmꢀ1. MS (FAB) m/z 515 (M+H)+. Anal. Calcd for
4.11. D-2,6-Di-O-acetyl-1-O-(p-methoxybenzyl)-3,4,5-tri-O-
[bis(2-cyanoethyl)phosphoryl]-myo-inositol (10)
To a solution of 9 (0.25 g, 0.66 mmol) in CH2Cl2 (10 ml) was
added
bis(2-cyanoethyl)
N,N-diisopropylphosphoramidite
(0.64 ml, 2.5 mmol) followed by 1H-tetrazole (0.21 g, 3.0 mmol),
and the resulting mixture was stirred at room temperature for
1.5 h. To the mixture was added m-chloroperbenzoic acid
(0.087 g, 0.51 mmol) in small portions and the resulting mixture
was stirred for 5 min. The mixture was diluted with CH2Cl2 and
washed with saturated aqueous NaHCO3. The organic phase was
dried over Na2SO4 and concentrated under reduced pressure. The
residue was purified by silica gel column chromatography
(CH2Cl2/MeOH = 12:1) to afford 10 (0.33 g, 54%) as a colorless oil.
1H NMR (CDCl3) d: 2.07 (3H, s), 2.21 (3H, s), 2.77–2.86 (12H, m),
3.61 (1H, d, J = 10.1 Hz), 3.80 (3H, s), 4.27–4.53 (16H, m), 4.81 (1H,
C28H34O9: C, 65.36; H, 6.66. Found: C, 65.06; H, 6.72.