K. Egusa, S. Kusumoto, K. Fukase
FULL PAPER
6.94 (dd, J ϭ 2.1, 8.1 Hz, 1 H, ClAzb), 7.05 (d, J ϭ 2.1 Hz, 1 H,
(5.00 g, 9.23 mmol) and benzyl bromide (2.41 mL, 20.3 mmol) in
ClAzb), 7.34Ϫ7.61 (m, 12 H, ArH), 7.92Ϫ8.01 (m, 8 H, ArH) ppm. DMF (20 mL) at 0 °C and the mixture was stirred for 2 h. The
13C NMR (75 MHz, CDCl3): δ ϭ 62.6 (C-6), 70.0 (C-4), 71.8 (C-
reaction was quenched by adding cold water (50 mL) and the prod-
2), 72.8 (C-5), 73.0 (ArCH2), 80.3 (C-3), 92.3 (C-1), 119.1, 127.1, uct was extracted twice with ethyl acetate. The combined organic
127.9, 128.12, 128.15, 128.6, 129.1, 129.3, 129.36, 129.40, 129.6, layers were washed with brine, dried with Na2SO4 and then concen-
129.8, 132.6, 133.1, 133.2, 133.4, 134.8, 136.0, 164.2 (CϭO), 164.31
trated in vacuo. The residue was purified by silica-gel column chro-
(CϭO), 164.35 (CϭO), 165.6 (CϭO) ppm. ESI-MS: m/z ϭ 784.1 matography (hexane/ethyl acetate, 5:1 Ǟ 2:1) to give 2 as white
[M ϩ Naϩ]. C41H32ClN3O10 (762.17): calcd. C 64.61, H 4.23, N crystals (6.20 g, 93%). M.p. 118Ϫ119 °C. TLC (hexane/ethyl acet-
1
5.51; found C 64.55, H 4.17, N 5.46.
ate, 2:1): Rf ϭ 0.74. [α]2D5 ϭ ϩ66.9 (c ϭ 0.51, CH2Cl2). H NMR
(300 MHz, CDCl3): δ ϭ 3.59 (m, 1 H, 5-H), 3.70Ϫ3.78 (m, 3 H, 3-
H, 4-H, 6-H), 3.82 (dd, J ϭ 2.1, 10.8 Hz, 1 H, 6-H), 4.48 (d, J ϭ
11.7 Hz, 1 H, ArCHH), 4.55 (d, J ϭ 11.7 Hz, 1 H, ArCHH), 4.62
(d, J ϭ 11.4 Hz, 2 H, ArCHH), 4.66 (d, J ϭ 11.7 Hz, 1 H,
ArCHH), 4.74 (d, J ϭ 9.9 Hz, 1 H, 1-H), 4.75 (d, J ϭ 11.1 Hz, 1
H, ArCHH), 5.19 (dd, J ϭ 9.3, 9.9 Hz,1 H, 2-H), 6.71 (d, J ϭ
8.1 Hz, 1 H, ClAzb), 6.97 (dd, J ϭ 2.1, 8.1 Hz, 1 H, ClAzb), 7.07
(d, J ϭ 1.8 Hz, 1 H, ClAzb), 7.16Ϫ7.35 (m, 13 H, ArH), 7.40Ϫ7.47
(m, 4 H, ArH), 7.55Ϫ7.62 (m, 1 H, ArH) 7.92Ϫ7.96 (m, 2 H, ArH)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 68.7 (C-6), 71.9 (C-2), 73.4
(ArCH2), 73.8 (ArCH2), 75.0 (ArCH2), 77.8 (C-4), 79.3 (C-5), 84.4
(C-3), 85.9 (C-1), 119.2, 124.3, 127.3, 127.4, 127.5, 127.6, 127.7,
128.2, 128.3, 128.6, 129.4, 129.5, 129.9, 132.4, 133.0, 135.6, 136.0,
137.5, 137.9, 164.7 (CϭO) ppm. ESI-MS: m/z ϭ 744.1 [M ϩ Naϩ].
C40H36ClN3O6S (722.25): calcd. C 66.52, H 5.02, N 5.82; found C
66.47, H 4.95, N 5.76.
Phenyl 3-O-(4-Azido-3-chlorobenzyl)-2,4,6-tri-O-benzoyl-1-thio-β-D-
glucopyranoside (9): A mixture of 8 (5.50 g, 7.22 mmol, α/β ϭ
5.5:1), phenylthiotrimethylsilane (2.05 mL, 10.8 mmol), ZnI2
(1.15 g, 3.61 mmol) and CH2Cl2 (20 mL) was stirred at room tem-
perature overnight. The mixture was filtered and the filtrate was
washed with hydrochloric acid (1 mol/L) and brine, dried with
Na2SO4 and then concentrated in vacuo. The residue was crys-
tallized from hexane/ethyl acetate to give 9 as white crystals (4.55 g,
84%). M.p. 131Ϫ132 °C. TLC (toluene/ethyl acetate, 10:1): Rf ϭ
0.62. [α]2D5 ϭ ϩ13.6 (c ϭ 0.53, CH2Cl2). 1H NMR (300 MHz,
CDCl3): δ ϭ 4.03 (t, J ϭ 9.0 Hz, 1 H, 3-H), 4.05 (ddd, J ϭ 3.0,
6.3, 9.9 Hz, 1 H, 5-H), 4.38 (dd, J ϭ 6.3, 12.3 Hz, 1 H, 6-H), 4.45
(s, 2 H, ArCH2), 4.64 (dd, J ϭ 3.0, 12.3 Hz, 1 H, 6-H), 4.90 (d,
J ϭ 9.9 Hz, 1 H, 1-H), 5.34 (dd, J ϭ 9.0, 9.9 Hz, 1 H, 2-H), 5.47
(dd, J ϭ 9.0, 9.9 Hz, 1 H, 4-H), 6.58 (d, J ϭ 8.1 Hz, 1 H, ClAzb),
6.87 (dd, J ϭ 2.1, 8.1 Hz, 1 H, ClAzb), 6.97 (d, J ϭ 2.1 Hz, 1
H, ClAzb), 7.05Ϫ7.10 (m, 2 H, ArH), 7.16Ϫ7.21 (m, 1 H, ArH),
7.39Ϫ7.64 (m, 11 H, ArH), 7.92Ϫ8.02 (m, 6 H, ArH) ppm. 13C
NMR (75 MHz, CDCl3): δ ϭ 63.1 (C-6), 70.4 (C-4), 71.8 (C-2),
73.0 (ArCH2), 75.9 (C-5), 81.8 (C-3), 86.0 (C-1), 119.0, 124.0,
127.1, 127.7, 128.0, 128.12, 128.15, 128.4, 128.6, 129.0, 129.2,
129.3, 129.4, 129.6, 131.7, 132.4, 132.8, 133.1, 133.2, 134.8, 135.9,
164.3 (CϭO), 164.4 (CϭO), 165.6 (CϭO) ppm. ESI-MS: m/z ϭ
772.2 [M ϩ Naϩ]. C40H32ClN3O8S (750.22): calcd. C 64.04, H 4.30,
N 5.60; found C 64.04, H 4.26, N 5.46.
4-(Hydroxymethyl)benzyl 3-O-(4-Azido-3-chlorobenzyl)-2-O-benzoyl-
4,6-di-O-benzyl-β-D-glucopyranoside (11): A mixture of 2 (1.50 g,
2.08 mmol), xylylene glycol (861 mg, 6.23 mmol), Sn(OTf)2
(216 mg, 0.52 mmol), 4-A molecular sieves (ca. 500 mg) and THF
˚
(25 mL) was stirred at room temperature for 15 min, then cooled
to 0 °C. N-Bromosuccinimide (388 mg, 2.18 mmol) was added, the
mixture was stirred for 30 min and then filtered. The filtrate was
concentrated in vacuo and the residue was purified by silica-gel
column chromatography (hexane/ethyl acetate, 2:1) to give 11 as
white crystals (1.17 g, 75%). M.p. 121Ϫ123 °C. TLC (hexane/ethyl
acetate, 1:1): Rf ϭ 0.45. [α]2D5 ϭ ϩ23.4 (c ϭ 0.53, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ ϭ 3.49 (ddd, J ϭ 2.4, 4.2, 9.6 Hz, 1
H, 5-H), 3.67 (t, J ϭ 9.2 Hz, 1 H, 3-H), 3.72Ϫ3.81 (m, 3 H, 4-H,
6-H, 6-H), 4.47 (d, J ϭ 12.0 Hz, 1 H, ArCHH), 4.49 (d, J ϭ 7.9 Hz,
1 H, 1-H), 4.55Ϫ4.68 (m, 7 H, ArCHH), 4.75 (d, J ϭ 11.1 Hz, 1
H, ArCHH), 4.84 (d, J ϭ 12.6 Hz, 1 H, ArCHH), 5.27 (dd, J ϭ
7.9, 9.2 Hz, 1 H, 2-H), 6.70 (d, J ϭ 7.8 Hz, 1 H, ClAzb), 6.98 (dd,
J ϭ 1.8, 8.1, ClAzb), 7.08 (d, J ϭ 1.8 Hz, 1 H, ClAzb), 7.10Ϫ7.21
(m, 6 H, ArH), 7.25Ϫ7.44 (m, 10 H, ArH), 7.55Ϫ7.61 (m, 1 H,
ArH), 7.84Ϫ7.88 (m, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 64.9 (ArCH2O), 68.4 (C-6), 69.7 (ArCH2), 73.2 (C-2), 73.4 (2
C, ArCH2 ϫ 2), 74.8 (ArCH2), 75.0 (C-5), 77.9 (C-4), 82.8 (C-3),
99.1 (C-1), 119.1, 124.0, 126.5, 127.2, 127.3, 127.4, 127.45, 127.52,
127.9, 128.0, 128.1, 129.3, 129.7, 132.7, 135.5, 135.8, 136.1, 137.4,
137.6, 139.8, 164.5 (CϭO) ppm. ESI-MS: m/z ϭ 772.3 [M ϩ Naϩ].
C42H40ClN3O8 (750.24): calcd. C 67.24, H 5.37, N 5.60; found C
67.23, H 5.28, N 5.49.
Phenyl 3-O-(4-Azido-3-chlorobenzyl)-2-O-benzoyl-1-thio-β-D-gluco-
pyranoside (10): Sodium methoxide (243 mg, 4.50 mmol) was added
to a solution of 9 (6.35 g, 8.46 mmol) in a mixture of methanol and
THF (1:2, 75 mL) at room temperature. After stirring for 2 h, the
mixture was neutralized with ion-exchange resin Amberlyst 15
(Hϩ form), then concentrated in vacuo. The residue was crys-
tallized from hexane/ethyl acetate to give 10 as white crystals
(4.22 g, 92%). M.p. 131Ϫ132 °C. TLC (hexane/ethyl acetate, 1:2):
Rf ϭ 0.49. [α]2D5 ϭ ϩ83.5 (c ϭ 0.51, CH2Cl2). 1H NMR (300 MHz,
CDCl3): δ ϭ 1.99 (t, J ϭ 6.8 Hz, 1 H, 6-OH), 2.50 (d, J ϭ 3.3 Hz,
1 H, 4-OH), 3.50 (ddd, J ϭ 3.6, 5.1, 9.0 Hz, 1 H, 5-H), 3.68 (t, J ϭ
9.0 Hz, 1 H, 3-H), 3.78 (dt, J ϭ 3.3, 9.0 Hz, 1 H, 4-H), 3.85 (ddd,
J ϭ 5.1, 6.8, 12.0 Hz, 1 H, 6-H), 3.96 (ddd, J ϭ 3.6, 6.8, 12.0 Hz,
1 H, 6-H), 4.58 (d, J ϭ 11.7 Hz, 1 H, ArCHH), 4.66 (d, J ϭ
11.7 Hz, 1 H, ArCHH), 4.82 (d, J ϭ 10.1 Hz, 1 H, 1-H), 5.20 (dd,
J ϭ 9.0, 10.1 Hz, 1 H, 2-H), 6.85 (d, J ϭ 8.1 Hz, 1 H, ClAzb), 7.05
(dd, J ϭ 2.1, 8.1 Hz, 1 H, ClAzb), 7.16 (d, J ϭ 2.1 Hz, 1 H, ClAzb),
7.24Ϫ7.29 (m, 3 H, ArH), 7.38Ϫ7.48 (m, 4 H, ArH), 7.57Ϫ7.63
(m, 1 H, ArH) 7.96Ϫ8.00 (m, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 62.2 (C-6), 70.3 (C-4), 71.7 (C-2), 73.4 (ArCH2), 79.1
(C-5), 83.9 (C-3), 86.2 (C-1), 119.2, 124.3, 127.0, 127.7, 128.1,
128.6, 129.1, 129.4, 129.7, 132.0, 132.1, 133.0, 135.3, 136.0, 164.6
(CϭO) ppm. ESI-MS: m/z ϭ 564.0 [M ϩ Naϩ]. C26H24ClN3O6S
(542.00): calcd. C 57.62, H 4.46, N 7.75; found C 57.32, H 4.38,
N 7.64.
4-{[(3-Carboxypropanoyl)oxy]methyl}benzyl 3-O-(4-Azido-3-chloro-
benzyl)-2-O-benzoyl-4,6-di-O-benzyl-β-D-glucopyranoside (12): Suc-
cinic anhydride (195 mg, 1.95 mmol) was added to a solution of 11
(977 mg, 1.30 mmol), dimethylaminopyridine (79 mg, 0.65 mmol)
and triethylamine (0.18 mL, 1.30 mmol) in CH2Cl2 (5 mL) at room
temperature and the mixture was stirred for 2 h, then washed with
hydrochloric acid (0.1 mol/L) and brine, dried with Na2SO4 and
concentrated in vacuo. Crystallization from hexane/ethyl acetate
Phenyl 3-O-(4-Azido-3-chlorobenzyl)-2-O-benzoyl-4,6-di-O-benzyl-
1-thio-β-
D
-glucopyranoside (2): NaH (60% suspension in oil, gave 12 as pale-yellow crystals (1.02 g, 92%). M.p. 125Ϫ128 °C.
812 mg, 20.3 mmol) was added in portions to a solution of 10
TLC (ethyl acetate): Rf ϭ 0.64. [α]2D5 ϭ ϩ26.6 (c ϭ 0.52, CH2Cl2).
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2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 3435Ϫ3445