then added and the reaction mixture was allowed to warm up to
room temperature in 10 minutes. The reaction was again cooled
to 0 ◦C, neutralized with 10% aqueous NaOH, extracted with
EtOAc, washed with water and brine, and dried over anhydrous
Na2SO4. After filtration and removal of all solvents under reduced
pressure, compound 2c was obtained by flash chromatography in
diluted with EtOAc. The organic phase was collected and washed
with saturated NaHCO3 and dried over Na2SO4. The residue was
purified by flash chromatography to give the compound 3a in 45%
yield for two steps (0.65 g). 1H NMR (600 MHz, CDCl3) d 3.57 (t,
1H, J1,2 = 9.6 Hz, H2), 3.58–3.61 (m, 1H, H5), 3.65–3.70 (m, 2H,
2 X H6), 3.75 (t, 1H, J = 9.6 Hz, H3), 3.78 (t, 1H, J = 9.6 Hz, H4),
4.52 (d, 1H, J = 11.4 Hz, PhCH2O), 4.57 (d, 1H, J = 11.4 Hz,
PhCH2O), 4.60 (d, 1H, J = 11.4 Hz, PhCH2O), 4.76 (d, 1H, J =
11.4 Hz, PhCH2O), 4.82 (q, 2H, J = 11.4 Hz, PhCH2O), 4.82 (d,
1H, J1,2 = 9.6 Hz, H1), 4.87 (d, 1H, J = 11.4 Hz, PhCH2O), 4.90
(d, 1H, J = 11.4 Hz, PhCH2O), 7.19–7.36 (m, 20H), 7.59–7.61 (m,
2H), 7.99–8.01 (m, 2H); 13C NMR (150 MHz, CDCl3) d 69.1, 73.7,
75.4, 75.9, 76.1, 77.9, 79.4, 80.9, 86.0, 86.8 (C1), 124.1, 128.0–129.6,
137.7, 138.0, 138.1, 138.4, 144.6, 146.4; MS (ESI) m/z calcd. for
C40H39NNaO7S [M + Na]+ 700.2; found 700.4; HRMS m/z calcd.
for C40H39NNaO7S [M + Na]+ 700.2345; found 700.2350.
1
87% yield (542 mg). H NMR (400 MHz, CDCl3) d 2.95 (s, 1H,
4-OH), 3.66-3.71 (m, 1H, H5), 3.76–3.88 (m, 3H, H2, H6, H6¢), 4.18
(t, 1H, J = 10.2 Hz, H3), 4.23 (t, 1H, J = 10.2 Hz, H4), 4.52 (d,
1H, J = 12.4 Hz, PhCH2O), 4.57 (d, 1H, J = 12.4 Hz, PhCH2O),
4.62 (d, 1H, J = 12.4 Hz, PhCH2O), 4.72 (d, 1H, J = 12.4 Hz,
PhCH2O), 5.47 (d, 1H, J = 10.2 Hz, H1), 6.82–7.84 (m, 18H); 13
C
NMR (100 MHz, CDCl3) d 54.6, 70.7, 74.0, 74.1, 74.8, 78.2, 79.9,
83.6 (C1), 119.6, 127.8–128.8, 135.1, 137.9, 138.1, 140.4, 167.8,
168.4; MS (ESI) m/z calcd. For C34H30N4NaO6S [M + Na]+ 645.2;
found 645.3; HRMS m/z calcd. For C34H30N4NaO6S [M + Na]+
645.1784; found 645.1790.
p-Bromophenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-glucopyrano-
side (3b). Compound 3b was prepared as described in the
synthesis of compound 3a starting from compound 6 in 92% yield.
1H NMR (600 MHz, CDCl3) d 3.48 (t, 1H, J1,2 = 9.6 Hz, H2), 3.50–
3.52 (m, 1H, H5), 3.63 (t, 1H, J = 9.6 Hz, H3), 3.70 (t, 1H, J =
9.6 Hz, H4), 3.69–3.71 (m, 1H, H6), 3.77 (dd, 1H, J = 1.8, 10.8 Hz,
H6¢), 4.53 (d, 1H, J = 12.0 Hz, PhCH2O), 4.58 (d, 2H, J = 12.0 Hz,
PhCH2O), 4.62 (d, 1H, J1,2 = 9.6 Hz, H1), 4.73 (d, 1H, J = 10.8 Hz,
PhCH2O), 4.81 (d, 1H, J = 10.8 Hz, PhCH2O), 4.83 (d, 1H, J =
10.8 Hz, PhCH2O), 4.84 (d, 1H, J = 12.0 Hz, PhCH2O), 4.88
(d, 1H, J = 10.8 Hz, PhCH2O), 7.18–7.20 (m, 2H), 7.27–7.37 (m,
20H), 7.43–7.44 (m, 2H); 13C NMR (150 MHz, CDCl3) d 69.2,
73.6, 75.3, 75.7, 76.1 (4 X OCH2Ph, C6), 78.0, 79.2, 80.9, 86.9,
87.6 (C1), 122.0, 127.9–128.7, 132.2, 133.0, 133.7, 138.1, 138.4,
138.5; MS (ESI) m/z calcd. for C40H39BrNaO5S [M + Na]+ 733.2;
found 733.4; HRMS m/z calcd. for C40H39BrNaO5S [M + Na]+
733.1599; found 733.1604.
p-N-Acetamidophenyl 2-deoxy-phthalimido-3,6-di-O-benzyl-1-
thio-b-D-gluco-pyranoside (2d). Compound 2f (59.7 mg,
0.1 mmol) was dissolved in MeOH (10 mL) at 0 ◦C. A solution of
acetic anhydride (47 mL, 0.5 mmol) was adde◦d to this solution and
the mixture was stirred for 10 minutes at 0 C, then the reaction
mixture was neutralized with solid NaHCO3, extracted with
EtOAc, washed with water and brine, and dried over anhydrous
Na2SO4. After filtration and removal of all solvents under reduced
pressure, compound 2d was obtained by flash chromatography in
97% yield (62.0 mg). 1H NMR (400 MHz, CDCl3) d 2.12 (s, 3H,
NHCOCH3), 3.19 (s, 1H, 4-OH), 3.64–3.68 (m, 1H, H5), 3.77–3.86
(m, 3H, H2, H6, H6¢), 4.18 (t, 1H, J = 9.6 Hz, H3), 4.22 (t, 1H, J =
9.6 Hz, H4), 4.51 (d, 1H, J = 12.4 Hz, PhCH2O), 4.54 (d, 1H, J =
12.4 Hz, PhCH2O), 4.59 (d, 1H, J = 12.4 Hz, PhCH2O), 4.72 (d,
1H, J = 12.4 Hz, PhCH2O), 5.46 (d, 1H, J = 9.6 Hz, H1), 6.91–7.83
(m, 18H), 7.57 (bs, 1H, NHAc); 13C NMR (100 MHz, CDCl3) d
29.8 (NHCOCH3), 54.6, 70.7, 74.0 (2 X OCH2Ph, C6), 74.2, 74.8,
78.1, 79.8, 84.0 (C1), 120.2, 123.6, 123.7, 128.0–128.8, 134.2–134.4,
137.9, 138.1, 138.4, 167.7, 168.4, 168.8; MS (ESI) m/z calcd. for
C36H34N2NaO7S [M + Na]+ 661.2; found 661.4; HRMS m/z calcd.
for C36H34N2NaO7S [M + Na]+ 661.1984; found 661.1976.
p-Azidophenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-glucopyrano-
side (3c). Compound 3c was prepared as described in the
synthesis of compound 3a starting from compound 9 in 78% yield.
1H NMR (600 MHz, CDCl3) d 3.46 (t, 1H, J1,2 = 9.6 Hz, H2), 3.47–
3.50 (m, 1H, H5), 3.63 (t, 1H, J = 9.6 Hz, H3), 3.70 (t, 1H, J =
9.6 Hz, H4), 3.71–3.73 (m, 1H, H6), 3.78 (d, 1H, J = 10.2 Hz, H6¢),
4.53 (d, 1H, J = 10.2 Hz, PhCH2O), 4.58 (d, 1H, J1,2 = 9.6 Hz, H1),
4.58–4.60 (m, 2H, PhCH2O), 4.73 (d, 1H, J = 10.2 Hz, PhCH2O),
4.81 (d, 1H, J = 10.8 Hz, PhCH2O), 4.84 (d, 1H, J = 10.2 Hz,
PhCH2O), 4.85 (d, 1H, J = 10.8 Hz, PhCH2O), 4.88 (d, 1H, J =
10.2 Hz, PhCH2O), 6.82–6.83 (m, 2H), 7.19–7.39 (m, 20H), 7.56–
7.57 (m, 2H); 13C NMR (150 MHz, CDCl3) d 69.2, 73.6, 75.3,
75.7, 76.1 (4 X OCH2Ph, C6), 78.0, 79.2, 80.9, 86.9, 87.6 (C1),
119.7, 127.9–128.7, 129.7, 134.3, 138.1, 138.2, 138.4, 138.5, 139.9;
MS (ESI) m/z calcd. for C40H39N3NaO5S [M + Na]+ 696.3; found
696.4; HRMS m/z calcd. for C40H39N3NaO5S [M + Na]+ 696.2508;
found 696.2501.
p-Nitrophenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-glucopyrano-
side (3a). To a 50 mL round-bottom flask were added the
tetraacetate 513 (1.11 g, 2.28 mmol) and a 2:3 mixture of MeOH-
CH2Cl2 (25 mL). The mixture was cooled to 0 ◦C, treated with
a 0.5 M NaOMe solution in MeOH (1.50 mL, 0.75 mmol)
and stirred for 10 minutes followed by warming up to room
temperature and further stirring for 2 hours. The reaction was
neutralized with acetic acid to pH around 7. The suspension was
concentrated under reduced pressure, diluted with CH2Cl2 and
filtered to afford the white solid tetraol (0.84 g). The crude tetraol
was dried under vacuum in a 25 ml round-bottom flask overnight
and azeotropically distilled in toluene to remove any residue water.
It was then suspended in anhydrous DMF (15 mL) with freshly
˚
activated MS 4 A (1 g). The suspension was stirred for 30 minutes
p-N-Acetamidophenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-gluco-
pyranoside (3d). Compound 3d was prepared as described in the
synthesis of compound 15 starting from compound 3a in 84%
yield. 1H NMR (600 MHz, CDCl3) d 2.17 (s, 3H, NHAc), 3.46 (t,
1H, J1,2 = 9.6 Hz, H2), 3.47–3.49 (m, 1H, H5), 3.62 (t, 1H, J =
9.6 Hz, H3), 3.69 (t, 1H, J = 9.6 Hz, H4), 3.70 (dd, 1H, J = 4.2,
10.8 Hz, H6), 3.75 (dd, 1H, J = 1.2, 10.8 Hz, H6), 4.53 (d, 1H,
at room temperature, then cooled to 0 ◦C in an ice-bath followed
by slow addition of 95% NaH (0.35 g, 13.8 mmol). The resulting
suspension was stirred for 30 minutes at 0 ◦C then treated with
BnBr (1.42 mL, 11.9 mmol). The mixture was warmed to room
temperature and stirred for another 4 hours. Then the mixture was
cooled back to 0 ◦C and quenched with acetic acid to pH = 7 and
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