4
.06 (1H, dd, J = 12.4, 2.2 Hz, H ), 3.72 (1H, ddd, J = 9.3, 4.6, 2.2 Hz, H ), 2.32 (1H, ddd, J
6b 5
=
12.6, 4.9, 2.3 Hz, H ), 2.09 (3H, s, C(O)CH ), 2.06 (3H, s, C(O)CH ), 2.02 (3H, s,
2 3 3
1
3
C(O)CH ), 2.01 (3H, s, C(O)CH ); C NMR (100 MHz, CDCl ) δ (β-anomer) 170.8 (C=O),
3
3
3
1
70.2 (C=O), 169.8 (C=O), 168.9 (C=O), 91.2 (C ), 72.9 (C ), 70.2 (C ), 68.4 (C ), 62.1 (C ),
1 5 4 3 6
3
4.8 (C ), 21.0 (C(O)CH ), 20.9 (C(O)CH ), 20.9 (C(O)CH ), 20.8 (C(O)CH ); HRMS m/z
2
3
3
3
3
+
+
(ESI ) Found: (M+Na) 355.1010, C H O Na requires 355.1005. Data matched those
14 20 9
[
34]
previously reported.
α-D
-Mannose 1-phosphate bis sodium salt 8
7
(250 mg, 0.64 mmol) gave 8 (91 mg, 0.35 mmol, 55%). Reaction temperature was 45 °C,
following purification as described in the General Experimental, the material was treated with
+
DOWEX-IR-120 (Na form) to obtain the bis-sodium salt form for comparison to reported
1
2
ꢀ
6
data. R 0.40 (acetonitrile/water/NH OH, 2/1/0.1); [α] +22.2 (c = 0.45, H O); H NMR (400
f
4
2
MHz, D O) δ 5.23 (1H, d, J = 8.5 Hz, H ), 3.87-3.74 (4H, m, H , H , H , H ), 3.66-3.59
2
1,P
1
2
3
5
6a
1
3
(
7
1H, m, H ) 3.50 (1H, app. t, J = 9.6 Hz, H ); C NMR (100 MHz, D O) δ 95.0 (C ), 73.0,
1.2, 70.2, 67.2 (C ), 61.3 (C ); P NMR (161 MHz, D O) δ 2.00 (1P, d, J = 8.5 Hz);
4 6 2 P,H
HRMS m/z (ES ) Found: (M-H) 259.0224, C H O requires 259.0231. Data matched those
previously reported.
6b 4 2 1
31
-
−
6
11
9
[
35]
1
,2,3,4,6-Penta-O-acetyl-5-C-Methyl-α/β-D-mannose 9
Acetylation using Ac O/pyridine
2
[
29]
5
-C-methyl-α/β-D-mannose (1.1 g, 5.8 mmol, 1.0 equiv.) was stirred in acetic anhydride
(20 mL) and pyridine (40 mL) for 18 hours at room temperature under a nitrogen atmosphere.
The reaction mixture was concentrated in vacuo and co-evaporated with toluene (3 x 20 mL).
TLC (3% MeOH in DCM) showed four spots (R 0.39–0.75) corresponding to the
f
diastereomeric pyranoside and furanoside forms. This residue was purified by silica gel
column chromatography to afford 9 as an inseparable mixture of pyranosides and α-
1
furanoside (>93% pyranoside by H NMR integration and a 58:35 β:α pyranoside ratio) as an
off-white solid (688 mg, 1.73 mmol, 67%). The β-furanoside was separable as a yellow, flaky
1
solid (91 mg, 0.23 mmol, 4%). H NMR (400 MHz, CDCl ) δ α-pyranoside 6.11 (1H, d, J =
3
2
.3 Hz, H ), 5.58 (1H, d, J = 10.5 Hz, H ), 5.25 (2H, dd, J = 10.2, 3.3 Hz, H , H ), 4.11−3.95
1 4 2 3
(
2H, m, H6a+b), 2.02 (3H, s, (C(O)CH ), 2.06 (3H, s, (C(O)CH ), 2.12 (3H, s, (C(O)CH ),
3 3 3
2
.14 (3H, s, (C(O)CH ), 2.17 (3H, s, (C(O)CH ), 1.39 (3H, s, CH ); β-pyranoside 6.06 (1H,
3 3 3
d, J = 1.4 Hz, H ), 5.48 (1H, d, J = 10.4 Hz, H ), 5.25 (2H, dd, J = 10.2, 3.3 Hz, H , H ),
1
4
2
3
4
.11−3.95 (2H, m, H6a+b) 2.01 (3H, s, (C(O)CH ), 2.05 (3H, s, (C(O)CH ), 2.10 (3H, s,
3 3
(
C(O)CH ), 2.12 (3H, s, (C(O)CH ), 2.21 (3H, s, (C(O)CH ), 1.40 (3H, s, CH ); α-furanoside
3 3 3 3
5
.41 (1H, s, H ), 5.21 (1H, m, H ) 4.99 (1H, dd, J = 5.6, 1.8 Hz, H ), 4.91 (1H, d, J = 1.8 Hz,
1
2
3
H ), 4.35, 3.56 (2H, q, J = 7.7 Hz, H
), 2.19 (3H, s, (C(O)CH ), 2.15 (3H, s, (C(O)CH ),
4
6a+6b
3
3
2
.07 (3H, s, (C(O)CH ), 1.98 (3H, s, (C(O)CH ), 1.34 (3H, s, CH ), β-furanoside 6.25 (1H, d,
3 3 3
J = 3.2 Hz, H ), 5.71–5.68 (1H, m, H ), 5.41 (1H, dd, J = 5.1, 3.2 Hz, H ), 4.27 (1H, d, J =
1
3
4
4
.3 Hz, H ), 4.15–4.14 (2H, m, H ), 2.11 (3H, s, (C(O)CH )), 2.10–2.10 (6H, m,
2 6a+b 3
13
(C(O)CH ), 2.07 (3H, s, (C(O)CH ), 1.29 (3H, s, CH ); C NMR (101 MHz, CDCl ) For
3 3 3 3
pyranoses δ 170.6, 170.5, 170.2, 170.0, 169.9, 169.7, 169.5, 169.4, 168.6, 168.4, 91.1 (C ),
1
β
8
2
6.8 (C ), 78.2 (C ), 76.1 (C ), 68.4, 68.3, 67.3 (C ), 67.2 (C ), 66.5, 21.2, 20.8, 20.8,
1α 5β 5α 6α 6β
+
+
0.8, 20.7, 20.6, 19.3 (CH ), 15.0 (CH ); HRMS m/z (ES ) Found: (M+Na) 427.1215,
3
-β
3-α
+
C H O Na requires (M+Na) 427.1217.
17
24 11
Acetylation using Ac O/H SO
2
2
4
To a stirred mixture of Ac O (850 µL, 9.0 mmol, 10.3 equiv.) and 5-C-methyl-α/β-D-
2
[
29]
mannose (170 mg, 0.87 mmol, 1.0 equiv.), H SO (1 drop) was added at 0 °C, under an
2
4
atmosphere of N . The solution was stirred for 10 min at 0 °C and then allowed to warm to
2
9