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T. Chaise et al. / Tetrahedron: Asymmetry 19 (2008) 348–357
135.7, 134.7, 131.5, 129.4, 127.9, 127.2, 126.4, 125.0 (C-
aro), 100.3 (PhCHO2), 96.0 (C-10), 87.8 (C-1), 86.6, 82.2
(C-3, C-30), 81.2, 80.5 (C-2, C-20), 78.9, 76.8 (C-4, C-40),
70.1, 70.0 (C-5, C-50), 68.0, 64.8 (C-6, C-60), 61.9, 59.9,
59.6, 59.2, 58.4, (2,20-OCH3, 3,30-OCH3, 6-OCH3).
solution was refluxed for 3 h. After evaporation under
reduced pressure, the residue (colorless oil) was used with-
out purification for the acetylation step.
Acetic anhydride (1.17 mL, 11.65 mmol), catalytic amounts
of triethylamine (17 lL) and 4-(N,N-dimethylamino)pyri-
dine (DMAP, 6 mg) were successively added to a CH2Cl2
solution (10 mL) of the crude product. The resulting mix-
ture was stirred at room temperature for 4 h, then was
diluted with CH2Cl2 (10 mL). The organic phase was suc-
cessively washed with 3 M aqueous solution of hydro-
chloric acid (2 ꢂ 5 mL), saturated aqueous solution of
sodium hydrogenocarbonate (2 ꢂ 5 mL) and brine (2 ꢂ
5 mL). After drying over Na2SO4 and evaporation under
reduced pressure, the crude product was purified by silica
gel column chromatography (toluene/acetone 80/20) to
give 0.37 g (yield: 24% for the three steps) of the desired
compound 8. Rf (toluene/acetone 50/50) = 0.57. HPLC/
MS: column HYPERSILÒ H5C18.25F; CH3OH/H2O 80/
20; rt = 17.04 min; calculated m/z 1399.62, found m/z
([M+Na]+) = 1399.12. Selected 1H NMR (300 MHz,
CDCl3) d: 7.45–7.39 (m, 2H, H-aro), 7.20–7.15 (m, 3H,
H-aro), 5.60 (m, 1H), 5.50–5.37 (m), 5.00 (d, 1H, J =
3.7 Hz), 4.20 (d, 1H, J = 9.7 Hz), 3.03–3.92 (m), 2.02 (s,
3H, Ac). Selected 13C NMR (75 MHz, CDCl3): 170.2
(COCH3), 134.2 (Cq, Ph), 131.8 (2 ꢂ CH, Ph), 129.1
(2 ꢂ CH, Ph), 127.2 (CH, Ph), 97.4, 96.9, 96.7, 95.5, 88.1,
87.0, 84.2, 83.4, 82.4, 82.1, 82.0, 80.2, 80.0, 73.5, 73.0,
72.8, 72.7, 71.3, 71.1, 70.8, 70.3, 70.0, 69.9, 69.8, 62.8,
62.6, 62.3, 62.2, 61.7, 61.6, 60.9, 60.7, 60.4, 60.1, 22.1
(CH3CO).
4.2.6. Phenyl 2,3,6-tri-O-methyl-4-O-(6-O-benzyl-2,3-di-O-
methyl-a-D-glucopyranosyl)-1-thio-b-D-gluco-pyranose
6
(Scheme 2). Sodium cyanoborohydride (295 mg,
4.70 mmol) was added portionwise to a suspension of com-
˚
pound 5 (278 mg, 0.47 mmol) and 4 A (50 mg) molecular
sieves in THF (5 mL). A saturated solution (ꢀ10 mL) of
hydrochloric acid in ether was added dropwise to the reac-
tion mixture until the disappearance of the starting mate-
rial (monitoring by TLC). After dilution with CH2Cl2
(50 mL), the reaction mixture was filtered, washed succes-
sively with aqueous solution of 3% (20 mL) ammonia and
water (20 mL). The resulting organic phase was dried over
MgSO4, filtered, and concentrated under reduced pressure.
The crude product was purified by silica gel column chro-
matography (EtOAc) to give 0.20 g (yield: 70%) of the
desired compound 6. Rf (EtOAc) =0.19. HPLC/MS: column
HYPERSILÒ H5C18.25F; CH3OH/H2O (90/10); rt =
1
4.06 min; m/z ([M+Na]+) = 617.10. H NMR (300 MHz,
CDCl3) d: 7.54–7.50 (m, 2H, H-aro), 7.34–7.26 (m, 8H,
3
H-aro), 5.60 (d, 1H, JH1,H2 = 3.6 Hz, H-1), 4.62 (d, 1H,
2
2Ja,b = 12.0 Hz, CHaHbPh), 4.53 (d, 1H, Ja,b = 12.0 Hz,
3
CHaHbPh), 4.51 (d, 1H, JH1 ,H2 = 9.7 Hz, H-10), 3.88–
3.64 (m, 6H, H-5, H-50, H-6, H-60), 3.64, 3.62, 3.59, 3.54
(s, 3H, 3-OCH3), (s, 3H, 30-OCH3), (s, 3H, 2-OCH3), (s,
3H, 20-OCH3), 3.59 (m, 1H, H-4), 3.54 (m, 1H, H-40),
0
0
3
3.37 (dd, 1H, JH3,H4 = 3JH3,H2 = 7.9 Hz, H-3), 3.41 (dd,
3
1H, JH3 ,H4 = 3JH3 ,H2 = 6.6 Hz, H-30), 3.29 (s, 3H,
4.2.8. 4-O-Acetyl-2,3,6-tri-O-methyl-a-D-glucopyranosyl-
[(1?4)-2,3,6-tri-O-methyl-a-D-glucopyranosyl]4-(1?4)-1-
deoxy-1-fluoro-2,3,6-tri-O-methyl-D-glucopyranose 9 (Scheme
3). (Diethylamino)sulfur trifluoride (DAST, 47 lL,
0.38 mmol) was added to a solution of compound 8
(372 mg, 0.27 mmol) in 1,2-dichloroethane (25 mL), at
ꢁ15 °C, under nitrogen atmosphere. After 2 min, N-bro-
mosuccinimide (NBS, 63 mg, 0.35 mmol) was added and
the resulting mixture was stirred at ꢁ15 °C for 25 min.
After warming at room temperature (1 h), the same
work-up as described for compound 8 (last step) was used.
The crude product was purified by silica gel column chro-
matography (toluene/acetate 50/50) to give 306 mg (yield:
88%) of the desired compound 9 as a mixture (1:1) of
a- and b-anomers. Rf (toluene/acetone 50/50) = 0.49.
HPLC/MS: column HYPERSILÒ H5C18.25F; from
CH3OH/H2O (50/50) to CH3OH (35 min); rt = 20.84 min
(anomer 1) and 21.57 min (anomer 2); calculated m/z
1309.61, found m/z ([M+Na]+) = 1310.01. 19F NMR
0
0
0
0
6-OCH3), 3.22 (dd, 1H, 3JH1,H2 = 3.6 Hz, 3JH2,H3 = 7.9 Hz,
3
3
0
0
0
0
H-2), 3.13 (dd, 1H, JH1 ,H2 = 9.7 Hz, JH2 ,H3 = 6.6 Hz,
H-20). 13C NMR (75 MHz, CDCl3) d: 137.2, 132.7, 130.8,
127.8, 127.4, 127.1, 126.9, 126.4 (C-aro), 95.4 (C-10), 87.7
(C-1), 86.3 (C-3, C-30), 82.6 (C-20), 82.1 (C-2), 77.1
(CH2Ph), 70.5, 70.3 (C-4, C-40), 67.5 (C-5, C-50), 60.7,
60.6 (C-6, C-60), 60.0, 59.6 (3-OCH3, 30-OCH3), 59.2
(6-OCH3), 58.8, 58.5 (2-OCH3, 20-OCH3).
4.2.7. Phenyl 4-O-acetyl-2,3,6-tri-O-methyl-a-D-glucopyran-
osyl-[(1?4)-2,3,6-tri-O-methyl-a-D-gluco-pyranosyl]4-(1?4)-
2,3,6-tri-O-methyl-1-thio-D-glucopyranose 8 (Scheme 3).
Zinc dibromide (1.02 g, 4.52 mmol) and phenylthio-
trimethylsilane (0.86 mL, 4.54 mmol) were added to a
solution of compound 713 (1.38 g, 1.13 mmol) in 1,2-dichlo-
roethane (DCE, 30 mL), under a nitrogen atmosphere. The
reaction mixture was stirred at room temperature for 5
days (orange-brown color) then poured into a mixture ice
water (ꢀ100 mL). The aqueous phase was extracted with
CHCl3 (2 ꢂ 30 mL). The combined organic layers were
washed successively with a saturated solution of sodium
hydrogenocarbonate (2 ꢂ 10 mL) and brine (2 ꢂ 10 mL).
After drying over Na2SO4, the solvents were removed
under reduced pressure. The crude product was used with-
out purification and characterization for the deprotection
step.
.
2
3
(282 MHz, CDCl3) d: ꢁ149.9 (dd, JF,H1 = 53.0, JF,H2
=
2
3
26.2 Hz), ꢁ136.8 (dd, JF,H1 = 53.0, JF,H2 = 12.1 Hz).
Selected 1H NMR data (300 MHz, CDCl3) d: 5.67 (d,
3
1H, JH1,H2 = 3.8 Hz, H-1), 5.56–5.41 (m, 4H, H-1), 5.30
(dd, 0.5H, JH1,F = 53.0 Hz, JH1,H2 = 6.3 Hz, H-1), 5.00
2
3
2
3
(dd, 0.5H, JH1,F = 53.0 Hz, JH1,H2 = 3.7 Hz, H-1), 4.22
(m, 1H, H-5), 3.87–3.61 (m, 18H, H-4, H-5, H-6), 3.58–
3.48 (m, 36H, 3-OCH3, 2-OCH3), 3.45–3.42 (m, 6H, H-
3), 3.40–3.31 (m, 18H, 6-OCH3), 2.09 (s, 3H, CH3CO). Se-
lected 13C data (75 MHz, CDCl3) d: 170.0 (CH3CO), 97.5,
96.9, 96.7, 95.5 (C-1), 88.1, 87.0, 84.2, 83.7, 82.4, 82.1, 82.0,
Next it was dissolved in MeOH (10 mL) and acetic acid
(0.86 mL, 14.69 mmol) was added, after which the resulting