38
E.C. Lourenço, M.R. Ventura/Carbohydrate Research 426 (2016) 33–39
J = 9.2 Hz, J = 10.1 Hz, H-2 (β)), 2.35 (s, 1H), 2.33 (s, 3H), 1.66 (d,
J = 0.3 Hz) ppm. 13C NMR (CDCl3): δ 139.0, 138.3, 137.74, 137.63,
137.53, 134.2, 133.1, 129.99, 129.93, 129.2, 128.59, 128.58, 128.55,
128.53, 128.25, 128.17, 128.06, 128.01, 127.94, 127.93, 126.9, 87.5
(C-1 (α)), 86.1 (C-1 (β)), 84.9 (C-3 (β)), 81.7 (C-3 (α)), 79.6 (C-5 (β)),
78.0 (C-4 (α)), 77.4 (C-4 (β)), 75.9 (CH2Ph (β)), 75.77 (CH2Ph (α)),
75.16 (CH2Ph (α)), 75.13 (CH2Ph (β)), 72.4 (C-5 (α)), 65.1 (C-2 (β)),
64.2 (C-2 (α)), 61.9 (C-6 (β)), 61.5 (C-6 (β)), 21.20 (CCH3 (β)), 21.16
(CCH3 (α)) ppm. HR-MS: calcd for C27H29ClN3O4SNa+ [M + Na]+:
514.1771; found: 514.1778.
4.10.3. Methyl (2S)-2-(2-azido-3,4,di-O-benzyl-6-O-chloroacetyl-2-
deoxy-α/β-D-glucopyranosyl)propanoate 11
FT-IR (film) υmáx.: 1742 (C
=
O), 2106 (N3) cm−1. 1H NMR (CDCl3):
δ 7.41–7.23 (m, Ph), 4.96–4.84 (m, CH2Ph), 4.93 (d, J = 3.4 Hz, H-1
(α)), 4.79 (d, J = 10.7 Hz, CH2Ph (β)), 4.62–4.56 (m, CH2Ph), 4.46–
4.39 (m), 4.45 (d, J = 7.9 Hz, H-1 (β)), 4.34–4.21 (m), 4.07 (dd,
J = 8.8 Hz, J = 10.3 Hz, H-3 (α)), 4.03–3.93 (m), 3.78 (s, CO2Me (β)),
3.73 (s, CO2Me (α)), 3.56 (dd, J = 8.9 Hz, J = 9.9 Hz, H-4 (α)), 3.48–
3.41 (m), 3.31 (dd, J = 3.7 Hz, J = 10.3 Hz, H-2 (α)), 1.47 (d, J = 6.8 Hz,
CHCH3) ppm. 13C NMR (CDCl3): δ 172.4, 166.8, 137.6, 137.5, 128.5,
128.1-128.0, 100.5 (C-1 (β)), 98.7 (C-1 (α)), 82.9 (β), 80.0 (C-3 (α),
77.3 (C-4 (α), 76.6 (β), 75.6 (β), 75.5 (α), 75.0 (α), 74.9, 72.8 (β), 72.4
(β), 69.5 (α), 65.9 (β), 64.1 (C-6 (β)), 64.0 (C-6 (α)), 63.1 (C-2 (α),
52.1 (CO2Me), 40.67 (COCH2Cl (α)), 40.65 (COCH2Cl (β)), 18.7 (CHCH3
(β)), 18.2 (CHCH3 (β)) ppm. HR-MS: calcd for C26H30ClN3O8Na+
[M + Na]+: 570.1614; found: 570.1603.
4.10. General glycosylation procedure
A suspension of thioglycoside donor (0.15 mmol), acceptor
(0.15 mmol) and 4Å MS in the solvent/mixture of solvents indi-
cated (1 mL) was stirred for 1 h at room temperature then cooled
to 0 °C. N-Iodosuccinimide (0.19 mmol) and TfOH (0.9 μL,
0.0102 mmol) were added at 0 °C. When the reaction was com-
plete (TLC), 10% Na2S2O3 aqueous solution (2 mL) and saturated
aqueous NaHCO3 (1 mL) were added and the reaction mixture was
extracted with CH2Cl2 (3 × 5 mL), the combined organic phases were
dried (MgSO4), filtered and the solvent was removed under vacuum.
The crude product was purified by preparative TLC (3:7, EtOAc/
Hex). The α/β ratio of the isolated product was measured by 1H NMR
(400 MHz, CDCl3) spectra.
4.10.4. Methyl 2-(2-azido-3,4,di-O-benzyl-6-O-chloroacetyl-2-
deoxy-α/β-D-glucopyranosyl)acetate 13
FT-IR (film) υmáx.: 1759 (C
=
O), 2110 (N3) cm−1. 1H NMR (CDCl3):
δ 7.40–7.26 (m, Ph), 5.02 (d, J = 3.5 Hz, H-1 (α)), 4.96–4.84 (m, CH2Ph),
4.81 (d, J = 10.6 Hz, CH2Ph (β)), 4.60 (d, J = 11.1 Hz, CH2Ph (α)), 4.55
(d, J = 12.0 Hz, CH2Ph (β)), 4.45 (d, J = 6.5 Hz, H-1 (β)), 4.38 (dd,
J = 3.6 Hz, J = 10.2 Hz, H-6 (α)), 4.31–4.25 (m), 4.18 (d, J = 16.6 Hz),
4.07–3.94 (m), 3.78 (s, CO2Me (β)), 3.77 (s, CO2Me (α)), 3.55 (dd,
J = 8.8 Hz, J = 10.0 Hz, H-4 (α)), 3.44 (dd, J = 3.6 Hz, J = 10.2 Hz, H-2
(α)) ppm. 13C NMR (CDCl3): δ 169.5, 166.8, 137.5, 137.3, 128.58,
128.55, 128.16, 128.13, 128.0, 101.2 (C-1 (β)), 97.8 (C-1 (α)), 80.2
(C-3 (α)), 77.2 (C-4 (α)), 75.6 (CH2Ph (α)), 75.0 (CH2Ph (α)), 72.8 (β),
69.6 (C-5 (α)), 65.9 (β), 64.3 (OCH2CO2Me (α)), 64.0 (C-6 (α)), 63.3
(C-2 (α)), 52.1 (CO2CH3 (α)), 40.6 (COCH2Cl (α)) ppm. HR-MS: calcd
for C25H28ClN3O8Na+ [M + Na]+: 556.1457; found: 556.1441.
4.10.1. Methyl (2S)-2-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-α/β-D-
glucopyranosyl)propanoate 9
FT-IR (film) υmáx.: 1752 (C
=
O), 2108 (N3) cm−1. 1H NMR (CDCl3):
δ 7.34–7.24 (m, Ph), 7.17–7.14 (m, Ph), 4.98 (d, J = 3.6 Hz, H-1 (α)),
4.90 (d, J = 10.6 Hz, CH2Ph), 4.87 (s, CH2Ph), 4.81–4.76 (m, CH2Ph),
4.59 (d, J = 12.0 Hz, CH2Ph), 4.54–4.42 (m, CH2Ph), 4.43 (d, J = 7.3 Hz,
H-1 (β)), 4.10 (dt, J = 2.4 Hz, J = 10.1 Hz, H-5 (α)), 4.05 (dd, J = 9.0 Hz,
J = 10.3 Hz, H-3 (α)), 3.78–3.72 (m, H-4 (α), H-6 (α)), 3.77 (s, CO2Me
(β)), 3.67 (s, CO2Me (α)), 3.60 (t, J = 9.1 Hz), 3.52 (dd, J = 1.9 Hz,
J = 10.8 Hz, H′-6 (α), 3.43 (t, J = 7.9 Hz, H-2 (β)), 3.34 (dd, J = 3.6 Hz,
J = 10.3 Hz, H-2 (α)), 1.50 (d, J = 6.9 Hz, CHCH3 (β)), 1.46 (d, J = 6.7 Hz,
CHCH3 (α)) ppm. 13C NMR (CDCl3): δ 172.6, 138.0-137.8, 128.5-
128.3, 128.0–127.6, 100.6 (C-1 (β)), 98.8 (C-1 (α)), 83.0 (β), 79.9 (C3
(α)), 78.1 (C-4 (α)), 77.5 (β), 75.5 (CH2Ph (β)), 75.3 (CH2Ph (α)), 75.05
(CH2Ph (β)), 75.04 (β), 74.9 (CH2Ph (α), CH2Ph (β)), 73.4 (CH2Ph (α)),
72.2 (β), 71.3 (C-5 (α), 68.5 (C-6 (β)), 68.0 (C-6 (α), 66.0 (β), 63.1
(C-2 (α), 52.1 (CO2Me (β)), 52.0 (CO2Me (α)), 18.8 (CHCH3 (β)), 18.1
(CHCH3 (α)) ppm. HR-MS: calcd for C31H35N3O7Na+ [M + Na]+:
584.2367; found: 584.2362.
4.10.5. Methyl (2R)-tert-butyldimethylsilyl-3-(2-azido-3,4,di-O-
benzyl-6-O-chloroacetyl-2-deoxy-α/β-D-glucopyranosyl)-2,3-
dihydroxyropanoate 15
FT-IR (film) υmáx.: 1743 (C
=
O), 2107 (N3) cm−1. 1H NMR (CDCl3):
δ 7.69–7.26 (m, Ph), 7.69–7.61 (m, Ph), 7.45–7.28 (m, Ph), 7.22–7.19
(m, Ph), 5.10 (d, J = 3.5 Hz, H-1 (α)), 4.93 (d, J = 10.4 Hz, CH2Ph (α)),
4.86 (d, J = 11.3 Hz, CH2Ph (α)), 4.83 (d, J = 10.4 Hz, CH2Ph (α)), 4.57
(d, J = 11.3 Hz, CH2Ph (α)), 4.46 (dd, J = 3.8 Hz, J = 6.6 Hz,
CHCH2OTBDPS), 4.40 (d, J = 8.1 Hz, H-1 (β)), 4.28–4.23 (m), 4.14.4.15
(m), 4.02–3.90 (m), 3.75 (s, CO2Me (α)), 3.54 (dd, J = 8.9 Hz, J = 9.8 Hz,
H-4 (α)), 3.38 (dd, J = 3.5 Hz, J = 10.3 Hz, H-2 (α)), 1.04 (s, t-Bu) ppm.
13C NMR (CDCl3): δ 169.6, 166.8, 137.65, 137.63, 135.6-135.5, 132.8,
132.7, 129.9, 129.8, 128.6, 128.5, 128.4, 128.1, 128.0, 127.88, 127.85,
127.78, 127.75, 96.3 (C-1 (α)), 80.0 (α), 75.63 (OCHCH2OTBDPS (α)),
75.60 (CH2Ph (α)), 74.8 (CH2Ph (α)), 69.2 (α), 64.4 (OCHCH2OTBDPS
(α)), 64.0 (C-6 (α)), 63.07 (C-2 (α)), 52.3 (CO2CH3 (α)), 40.5 (COCH2Cl
(α)), 26.7 (t-Bu (α)), 19.1 (C-Si (α)) ppm. HR-MS: calcd for
C42H48ClN3O9SiNa+ [M + Na]+: 824.2741; found: 824.2739.
4.10.2. Methyl (2S)-2-(6-O-acetyl-2-azido-3,4,di-O-benzyl-2-deoxy-
α/β-D-glucopyranosyl)propanoate 10
FT-IR (film) υmáx.: 1741 (C = O), 2107 (N3) cm−1. 1H NMR (CDCl3):
δ 7.39–7.23 (m, Ph), 4.95 (d, J = 3.7 Hz, H-1 (α)), 4.93–4.83 (m, CH2Ph),
4.78 (d, J = 10.7 Hz, CH2Ph (β)), 4.59–4.54 (m, CH2Ph), 4.48–4.43 (m),
4.44 (d, J = 7.8 Hz, H-1 (β)), 4.33–4.14 (m, H-5 (α), H-6 (α), H′-6 (α),
CHCH3) 4.07 (dd, J = 8.8 Hz, J = 10.3 Hz, H-3 (α)), 3.73 (s, CO2Me (α)),
3.78 (s, CO2Me (β)), 3.57 (dd, J = 8.9 Hz, J = 9.8 Hz, H-4 (α)), 3.45–
3.41 (m), 3.32 (dd, J = 3.7 Hz, J = 10.3 Hz, H-2 (α)), 2.03 (Ac (β)), 2.02
(Ac (α)), 1.48 (d, J = 6.9 Hz, CHCH3 (β)), 1.47 (d, J = 6.8 Hz, CHCH3 (α))
ppm. 13C NMR (CDCl3): δ 172.4, 170.6, 137.8 (β), 137.7 (α), 137.6 (α),
137.4 (β), 128.54, 128.51, 128.0, 127.9, 100.6 (C-1 (β)), 98.7 (C-1 (α)),
82.9 (β), 79.8 (C-3 (α)), 77.8 (C-4 (α), 77.1 (β), 75.6 (CH2Ph (β)), 75.4
(CH2Ph (α)), 75.09 (CH2Ph (β)), 75.02 (CH2Ph (α)), 74.9 (α), 73.0 (β),
72.4 (β), 69.7 (α), 66.0 (β), 63.1 (C-2 (α), 62.7 (C-6 (β)), 62.5 (C-6
(α)),52.1 (CO2Me), 20.8 (Ac), 18.7 (CHCH3 (β)), 18.2 (CHCH3 (α)) ppm.
HR-MS: calcd for C26H31N3O8Na+ [M + Na]+: 536.2003; found:
536.1998.
4.10.6. Methyl 3-O-tert-butyldiphenylsilyl-(2R)-2-O-[2-azido-3,4,di-
O-benzyl-6-O-chloroacetyl-2-deoxy-α-D-glucopyranosyl-(1→6)-
2,3,4-tri-O-benzyl-1-O-α-D-glucopyranosyl]-2,3-
dihydroxypropanoate 17
FT-IR (film) υmáx.: 1752 (C
=
O), 2108 (N3) cm−1. 1H NMR (CDCl3):
δ 7.72–7.69 (m, 3H), 7.46–7.44 (m, 2H), 7.39–7.20 (m, 30H), 5.21 (d,
1H, J = 3.5 Hz, H-1 (2)), 5.03–4.83 (m, 6H, CH2Ph), 4.92 (d, 1H,
J = 2.8 Hz, H-1 (1)), 4.75 (d, 1H, J = 10.7 Hz, CH2Ph), 4.70 (d, 1H,
J = 11.5 Hz, CH2Ph), 4.59–4.52 (m, 3H, CH2Ph, CHCH2OTBDPS), 4.22
(dd, 1H, J = 2.0 Hz, J = 12.0 Hz, H-6 (1)), 4.14–4.03 (m, 3H, H′-6 (1),
H-3 (2), CHCHH’OTBDPS), 4.00–3.90 (m, 3H, H-3 (1), H-5 (2),
CHCHH’OTBDPS), 3.87 (s, 2H, COCH2Cl), 3.74–3.71 (m, 5H, H-5 (1),
H-6 (2), CO2Me), 3.66–3.60 (m, 2H, H-2 (2), H-4 (2)), 3.52–3.46 (m,
2H, H-4 (1), H′-6 (2)), 3.28 (dd, 1H, J = 3.5 Hz, J = 10.3 Hz, H-2 (1)),