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H.-M. Chen, S. G. Withers / Carbohydrate Research 345 (2010) 2596–2604
(400 MHz, CDCl3): d 8.09–7.86 (m, 6H, Ar-H), 7.65–7.08 (m, 14H,
Ar-H), 5.72 (dd, 1H, J3,4 10.9 Hz, H-3), 5.41 (t, 1H, J2,3 9.6 Hz, H-2),
4.99 (d, 1H, J1,2 10.0 Hz, H-1), 4.75 (dd, 1H, J5,6a 1.8 Hz, J6a,6b
12.1 Hz, H-6a), 4.51 (dd, 1H, J5,6b 5.9 Hz, H-6b), 4.14 (m, 1H, H-5),
4.02 (t, 1H, J4,5 11.1 Hz, H-4), 2.19 (s, 3H, CH3CO). 13C NMR
(75 MHz, CDCl3): d 192.8, 166.3, 165.9, 165.3, 133.5, 133.4, 133.1,
132.2, 130.0, 129.9, 129.4, 129.0, 128.7, 128.5, 128.3, 86.3, 77.1,
73.1, 71.7, 64.2, 44.7; 30.9. ESI-HRMS: calcd for [C35H30O8S2+Na]+:
665.1280. Found m/z: 665.1287. Anal. Calcd for C35H30O8S2: C,
65.40; H, 4.70. Found: C, 65.67; H, 4.84.
3.69 mmol, 4.2 equiv) in CH2Cl2 (5 mL) was added dropwise with
stirring under N2. The yellow solution was stirred for 2 h while
allowing to gradually warm to 10 °C, diluted with CH2Cl2
(50 mL), washed with cold 1 M HCl (40 mL), cold satd NaHCO3
(40 mL) and brine (40 mL). The organic phase was then dried over
MgSO4, filtered and concentrated, dried under vacuum to give a
yellowish foam. To this yellow foam were added anhydrous CH3CN
(17 mL) and potassium thioacetate (0.2 g, 1.75 mmol, 2.0 equiv)
under N2. The reaction mixture was stirred at room temperature
for 15 min, diluted with ethyl acetate (200 mL), washed with brine
(2 ꢃ 100 mL), and dried over MgSO4. After concentration, the
resulting residue was purified by flash column chromatography
(4:1 petroleum ether–ethyl acetate) to give 23 as a white solid in
81% yield (0.5 g). 1H NMR (300 MHz, CDCl3): d 8.06 (m, 6H, Ar-
H), 7.65 (m, 2H, Ar-H), 7.52 (m, 4H, Ar-H), 7.12 (m, 2H, Ar-H),
5.89 (t, 1H, J3,4 = J2,3 10.4 Hz, H-3), 5.39 (d, 1H, J1,2 7.8 Hz, H-1),
5.18 (dd, 1H, H-2), 4.78 (br d, 1H, H-6a), 4.54 (dd, 1H, J5,6b 7.0,
J6a,6b 12.0, H-6b), 4.40 (m, 1H, H-5), 4.00 (t, 1H, H-4). 13C NMR
(75 MHz, CDCl3): d 192.7, 166.1, 165.5, 160.7, 143.8, 134.2, 134.0,
130.2 (2C), 129.9 (2C), 129.5, 128.9 (4C), 128.4, 126.0 (2C), 117.1
(2C), 118.5 (q), 97.5, 82.7, 73.4, 70.0, 63.5, 45.1, 31.0. ESI-HRMS:
calcd for [C29H24F3NO12S2+Na]+: 722.0590. Found m/z: 722.0598.
3.3.5. Phenyl-1,4-dithio-b-D-glucopyranoside (19)
Argon was bubbled through a suspension of 18 (0.3 g, 0.47 mmol)
in dry MeOH (15 mL) for 0.5 h at room temperature, followed by
addition of sodium methoxide solution (0.25 mL, 5.4 M, 1.35 mmol,
2.9 equiv). The reaction mixture was stirred for 48 h under argon at
room temperature, neutralized with IR-120 (H+) ion exchange resin,
filtered, washed with MeOH and concentrated in vacuo until 3 mL of
solvent remained. DTT (0.36 g in 15 mL of distilled water) was added
to this solution while stirring. Argon was bubbled through the reac-
tion mixture for another half an hour, then was stirred overnight at
room temperature. After concentration in vacuo, the resulting resi-
due was purified by flash column chromatography (15:1 and 9:1
CHCl3–CH3OH) to give 19 (105 mg, 78%) as a white powder. ½a D22
ꢂ
3.4.3. p-Nitrophenyl 4-S-thioethyl-4-thio-3,6-di-O-benzoyl-2-O-
triflate-b-D-gluco-pyranoside (24)
ꢀ53.4 (c 3.0, CH3OH). 1H NMR (400 MHz, CD3OD): d 7.50 (m, 2H,
Ar-H), 7.21 (m, 3H, Ar-H), 4.58 (d, 1H, J1,2 9.5 Hz, H-1), 3.83 (dd,
1H, J5,6a 2.0 Hz, J6a,6b 12.2 Hz, H-6a), 3.72 (dd, 1H, J5,6b 4.9 Hz,
H-6b), 3.33 (m, 1H, H-5), 3.27–3.12 (m, 2H, H-2 and H-3), 2.69
(t, 1H, J3,4 = J4,5 10.2 Hz, H-4). 13C NMR (75 MHz, CD3OD): d 135.3,
132.8, 130.0, 128.4, 89.4, 83.4, 80.5, 74.7, 63.5, 43.3. ESI-HRMS: calcd
for [C12H16O4S2+Na]+: 311.0388. Found m/z: 311.0380. Anal. Calcd
for C12H16O4S2: C, 49.98; H, 5.59. Found: C, 49.70; H, 5.76.
Compound 23 (0.48 g, 0.69 mmol) was dissolved in dry DMF
(9 mL), and N2 was bubbled through the solution for 15 min. To
this solution was added hydrazine acetate (126 mg, 1.4 mmol,
2 equiv), and the mixture was stirred for 0.5 h at room tempera-
ture. The reaction mixture was diluted with ethyl acetate
(100 mL), washed with water (50 mL) and brine (50 mL), dried over
MgSO4, filtered and concentrated and dried under vacuum. To the
residue was added CH2Cl2 (25 mL), diisopropyl-N-ethylsulfanyl
hydrazodicarboxylate (0.48 g, 1.82 mmol, 2.6 equiv) and 3 drops
of ammonium hydroxide, and the mixture was stirred for 20 min
at room temperature. The reaction mixture was diluted with
CH2Cl2 (100 mL), washed with cold 1 M HCl (50 mL), cold satd
NaHCO3 (50 mL) and cold brine (50 mL). The organic phase was
dried over MgSO4, filtered and concentrated. The resulting residue
was purified by flash column chromatography (5:1 petroleum
ether–ethyl acetate) to give 24 in 89% yield (438 mg). 1H NMR
(400 MHz, CDCl3): d 8.06 (m, 6H, Ar-H), 7.66 (m, 2H, Ar-H), 7.51
(m, 4H, Ar-H), 7.12 (m, 2H, Ar-H), 5.88 (t, 1H, J3,4 = J2,3 10.3 Hz,
H-3), 5.38 (d, 1H, J1,2 7.8 Hz, H-1), 5.18 (dd, 1H, H-2), 5.05 (dd,
1H, J5,6a 2.0 Hz, H-6a), 4.66 (dd, 1H, J5,6b 7.3, J6a,6b 12.1, H-6b),
4.33 (m, 1H, H-5), 3.15 (t, 1H, J4,5 10.7 Hz, H-4), 2.78 (m, 2H,
SCH2CH3), 1.20 (t, 3H, J 7.3 Hz, SCH2CH3). 13C NMR (100 MHz,
CDCl3): d 166.0, 165.3, 160.7, 143.8, 134.1, 133.9, 130.1 (2C),
129.9 (2C), 129.5, 128.83 (2C), 128.80 (2C), 128.7, 125.9 (2C),
117.1 (2C), 118.5 (q), 97.3, 83.0, 74.6, 70.1, 63.7, 52.0, 33.8, 14.4.
ESI-HRMS: calcd for [C29H26F3NO11S3+Na]+: 740.0518. Found m/z:
740.0526.
3.4. Preparation of p-nitrophenyl 4-thio-b-D-mannopyranoside
(27) and p-nitrophenyl 2-acetamido-2-deoxy-4-thio-b-D-
mannopyranoside (30)
3.4.1. p-Nitrophenyl 3,6-di-O-benzoyl-b-D-galactopyranoside (21)
A suspension of p-nitrophenyl b- -galactopyranoside (20, 0.70 g,
D
2.33 mmol) and dibutyltin oxide (1.33 g, 5.34 mmol, 2.3 equiv) in
dry MeOH (70 mL) was refluxed for 2 h. The homogenous solution
was concentrated and co-evaporated with toluene twice, and the
resulting residue was dried under vacuum for 1 h. The residue was
suspended in toluene (30 mL), and a solution of benzoyl chloride
(0.59 mL, 2.2 equiv) in toluene (3 mL) was added dropwise at 0 °C
with stirring under N2, gradually warmed to room temperature
and stirred overnight. The reaction mixture was diluted with ethyl
acetate, cooled to 0 °C and filtered through a short pad of Celite,
washed with cold ethyl acetate. After evaporation, the resulting res-
idue was purified by flash column chromatography (10:1 CH2Cl2–
EtOAc) to give 21 as a white solid in 61% yield (0.72 g). ½a D22
ꢂ
+ 12.7
(c 1.4, acetone). 1H NMR (400 MHz, DMSO-d6 + D2O): d 8.03 (m,
6H, Ar-H), 7.68 (m, 2H, Ar-H), 7.55 (m, 4H, Ar-H), 7.24 (m, 2H, Ar-
H), 5.40 (d, 1H, J1,2 7.7 Hz, H-1), 5.10 (dd, 1H, J3,4 3.2 Hz, H-3), 4.54
(dd, 1H, J5,6a 8.4 Hz, J6a,6b 10.8 Hz, H-6a), 4.39 (m, 2H, H-5 and 6b),
4.19 (d, 1H, H-4), 4.12 (d, 1H, J2,3 9.6 Hz, H-2). 13C NMR (100 MHz,
DMSO-d6 + D2O): d 167.1, 166.9, 163.3, 143.1, 135.0, 134.8, 131.3,
131.0, 130.9, 130.7, 130.1, 130.0, 126.9, 117.9 (2C), 100.9, 77.6,
74.1, 68.7, 67.1, 65.2. ESI-HRMS: calcd for [C26H23NO10+Na]+:
532.1220. Found m/z: 532.1208.
3.4.4. p-Nitrophenyl 2-O-acetyl-4-S-thioethyl-4-thio-3,6-di-O-
benzoyl-b-D-manno-pyranoside (25a)
A mixture of 24 (165 mg, 0.23 mmol), CH3CN (4 mL) and
TBAOAc (210 mg, 0.70 mmol, 3 equiv) was stirred for 1.5 h at
40 °C under N2. After evaporation, the resulting residue was di-
rectly purified by flash column chromatography (4:1 petroleum
ether–ethyl acetate) to give 25a in 82% yield (118 mg). ½a D22
ꢂ
+14.8 (c 0.8, CHCl3). 1H NMR (400 MHz, CDCl3): d 8.05 (m, 6H,
Ar-H), 7.63 (m, 2H, Ar-H), 7.48 (m, 4H, Ar-H), 7.06 (m, 2H, Ar-H),
5.95 (d, 1H, J2,3 2.7 Hz, H-2), 5.55 (dd, 1H, J3,4 10.9 Hz, H-3), 5.45
(s, 1H, H-1), 5.11 (dd, 1H, J5,6a 2.2 Hz, J6a,6b 11.8 Hz, H-6a), 4.65
(dd, 1H, J5,6b 7.7, H-6b), 4.29 (m, 1H, H-5), 3.25 (t, 1H, H-4), 2.74
(m, 2H, SCH2CH3), 2.21 (s, 3H, CH3CO), 1.20 (t, 3H, J 7.3 Hz,
3.4.2. p-Nitrophenyl 4-S-acetyl-3,6-di-O-benzoyl-2-O-triflyl-b-D-
glucopyranoside (23)
A solution of 21 (0.448 g, 0.88 mmol) in anhydrous CH2Cl2
(15 mL) and anhydrous pyridine (2 mL) was cooled to ꢀ20 °C,
and a solution of trifluoromethanesulfonic anhydride (0.62 mL,