The Journal of Organic Chemistry
Page 6 of 10
solution (10.0 mL), a catalytic amount of BnBr (0.15 mmol) was
added and stirred for 24h at room temperature. Ethyl acetate was
added to the reaction mixture, the organic layer was separated, dried
(2C), 127.8, 127.6, 112.4, 109.6, 104.9, 82.3, 81.7, 81.5, 79.6, 72.3,
72.1, 67.2, 36.6, 36.5, 35.7, 34.9, 25.2, 24.9, 24.1, 23.9, 23.9, 23.6.
2,3:5,6 Di-O-isopropylidene-D-manno-furanose (1f). white solid,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
4
2
1
over anh. Na
2
SO
4
, concentrated and purified using silica gel flash
89%; (1.84 g); mp 121-125 °C; H NMR (500 MHz, CDCl
(ppm):5.38 (s, 1H), 4.82 (dd, 1H, J = 3.5 Hz, J = 5.5 Hz), 4.62 (d,
1H, J = 5.5 Hz), 4.41 (dd, 1H, J = 5.8 Hz, J = 11.5 Hz), 4.19 (dd,
1H, J = 3.5 Hz, J = 7.6 Hz), 4.11-4.03 (m, 2H), 2.80 (d, 1H, J = 2.2
Hz), 1.48 (s, 3H), 1.47 (s, 3H), 1.39 (s, 3H), 1.33 (s, 3H); C{ H}
NMR (125 MHz, CDCl ) δ (ppm): 112.6, 109.1, 101.1, 85.4, 80.2,
3
) δ
column chromatography to form diol 16a and lactone 16b.
Characterization data of compound 16a and 16b:
1
2
1
2
tert-butyl
((3aR,5S,6R,6aR)-6-cyano-5-((R)-1,2-dihydroxyethyl)-
1
2
1
3
1
2
,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl)carbamate (16a):
1
colorless semisolid, 85% (357 mg); H NMR (500 MHz, CDCl
3
) δ
ppm): 5.95 (d, 1H, J = 3.6 Hz), 5.68 (br s, 1H), 5.08 (s, 1H), 4.12
dd, 1H, J = 3.6 Hz, J = 9.3 Hz), 3.90 (d, 2H, J = 9.3 Hz), 3.73 (dd,
= 5.1 Hz, J = 11.2 Hz), 1.56 (s, 3H), 1.49 (s, 5H), 1.37 (s,
3
(
(
79.6, 73.2, 66.5, 26.8, 25.8, 25.1, 24.4.
1
2
1-O-Benzyl-2,3:5,6-di-O-isopropylidene-α-D-manno-furanose
4
3
1
1H, J
1
2
(1g). white crystal; 82% (2.16 g); mp 81-83 °C; H NMR (500
MHz, CDCl ) δ (ppm):7.37-7.29 (m, 5H), 5.07 (s, 1H), 4.80 (dd, 1H,
= 4.2 Hz, J = 5.5 Hz), 4.66 (d, 1H, J = 5.5 Hz), 4.63 (s, 1H), 4.48
(dd, 1H, J = 5.5, J = 7.8 Hz), 4.43-4.38 (m, 1H), 4.11 (t, 1H, J = 7.8
Hz), 3.98-3.90 (m, 2H), 1.46 (s, 6H), 1.38 (s, 3H), 1.32 (s, 3H).
H} NMR (125 MHz, CDCl ) δ (ppm): 137.3, 128.5-127.8 (5C),
1
3
1
3
H), 1.25 (s, 4H); C{ H} NMR (125 MHz, CD
3
OD) δ (ppm):
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
7
56.2 (Boc, C=O), 113.0 (CN), 107.0, 106.9, 85.4, 84.7, 82.5, 80.1,
J
1
2
2
5
2.4, 64.9, 28.1 (3C), 27.2 (2C); [훼]퐷 32.0 (c = 0.9, CHCl
); FTIR
1
2
3
(
KBr): 3414 (OH, NH), 1731.1 (>C=O Boc) and 2242 (less intense
-1
+
+
13C{
1
CN) cm ; LC-MS (ESI ) m/z [C15
H24NaN
2
O
7
]
367.15; Found
3
367.24; Elemental analysis Anal. Calcd for C15H24N2O7: C, 52.32;
H, 7.02; N, 8.13. Found: C, 52.49; H, 7.15; N, 8.21.
112.6, 109.3, 105.6, 85.1, 80.4, 79.5, 73.1, 69.1, 66.9, 26.9, 25.8,
25.2, 24.5.
4
4
tert-butyl
((3aR,4aS,5R,8aR,8bR)-5-hydroxy-2,2-dimethyl-8-
1,2:5,6-Di-O-isopropylidene-α-D-galactofuranose (1h). colorless,
1
oxotetrahydro-6H-[1,3]dioxolo[4',5':4,5]furo[3,2-c]pyran-8a(8H)-
3
viscous liquid; 55% (1.95 g); H NMR (500 MHz, CDCl ) δ (ppm):
1
5.81 (s, 1H), 4.49 (s, 1H), 4.29-4.23 (m, 1H), 4.00-3.98 (m, 2H),
yl)carbamate (16b): colorless semisolid, 10% (41 mg); H NMR
(
500 MHz, CDCl
3
) δ (ppm): 5.94 (d, J = 3.4 Hz, 1H), 5.76 (br s, 1H),
3.75 (m, 1H), 3.73 (br t, 1H, J = 7.2 Hz), 1.46 (s, 3H), 1.36 (s, 3H),
1
3
1
4.84 (s, 1H), 4.75 (d, 1H, J = 3.4 Hz), 4.50-4.45 (m, 1H), 4.02 (dt,
3
1.29 (s, 3H), 1.25 (s, 3H); C{ H} NMR (125 MHz, CDCl ) δ
1
1
H, J = 3.4, 11.6 Hz), 3.94-3.89 (m, 1H), 3.21 (s, 1H), 1.60 (s, 3H),
.44 (s, 12H); C{ H} NMR (125 MHz, CDCl ) δ (ppm): 172.2
3
(ppm): 113.1, 109.7, 105.0, 87.3, 86.8, 75.6, 68.3, 65.6, 27.1, 26.4,
25.8, 25.3.
1
3
1
(1i).45
(
lactone C=O), 154.9 (Boc, C=O), 114.6, 105.2, 85.7, 84.0, 83.8,
1,2:3,5-Di-O-isopropylidene-α-D-xylofuranose
colorless
25
1
2.1, 66.8, 62.0, 28.1 (3C), 27.3, 27.2; [훼]퐷 +45.0 (c = 1.3, CHCl
FTIR (KBr): 3432.2 (OH, NH), 1784.9 (C=O lactone), 1710.1 (C=O
3
);
solid, 60% (1.77 g); mp 43-45 °C; H NMR (500 MHz, CDCl ) δ
3
8
(ppm):6.00 (d, 1H, J = 3.4 Hz), 4.52 (d, 1H, J = 3.3 Hz), 4.26 (br s,
1H), 4.13-4.01 (m, 3H), 1.49 (s, 3H), 1.44 (s, 3H), 1.38 (s, 3H), 1.32
-1
+
+
Boc) cm ; LC-MS (ESI ) m/z [C15
H23NaNO
8
]
368.13, Found
1
3
1
(
9
s, 3H); C{ H} NMR (125 MHz, CDCl
7.4, 84.6, 73.1, 71.6, 60.1, 28.9, 26.7, 26.1, 25.9.
Methyl 4,6-benzylidene-β-D-glucopyranoside (1j). white solid,
3
) δ (ppm): 111.6, 105.2,
3
68.19; Elemental analysis Anal. Calcd for C15H23NO8: C, 52.17;
H, 6.71; N, 4.06. Found: C, 52.29; H, 6.81; N, 4.11.
Preparation and characterization of starting materials:
Characterization data of compounds (1a-1j):
46
1
87% (2.30 g); mp 197-201 °C; H NMR (500 MHz, CDCl
(ppm):7.39 (d, 2H, J = 8.4 Hz), 7.26 (s, 1H), 6.80 (d, 2H, J = 8.7
Hz), 5.47 (s, 1H), 4.76 (d, 1H, J = 3.5 Hz), 4.26 (dd, 1H, J = 4.2 Hz,
= 10.1 Hz), 3.90 (t, 1H, J = 10.1 Hz), 3.80 (s, 3H), 3.78-3.74 (m,
3
) δ
3
7
1,2:5,6-Di-O-isopropylidene-α-D-glucofuranose (1a). white solid,
1
1
7
5
1
2
7% (15.0 g); mp 107-110 °C; H NMR (500 MHz, CDCl
.95 (br s, 1H), 4.54 (br s, 1H), 4.38-4.31 (m, 2H), 4.20-4.14 (m,
H), 4.09-4.05 (m, 1H), 3.97 (dd, 1H, J = 4.6 Hz, J = 9.4 Hz),
.70 (s, 1H), 1.50 (s, 3H), 1.44 (s, 3H), 1.36 (s, 3H), 1.32 (s, 3H);
3
) δ (ppm):
J
1
2
13
1
H), 3.72 (d, 1H, J = 10.1 Hz), 3.47 (s, 3H); C{ H} NMR (125
) δ (ppm): 160.3, 129.4, 127.5, 113.6, 101.8, 99.8, 96.1,
1
2
MHz, CDCl
3
1
3
1
80.8, 72.8, 71.8, 68.8, 62.3, 55.5, 55.2.
Characterization data of compounds (3a-3d):
C{ H} NMR (125 MHz, CDCl
85.1, 81.1, 75.2, 73.4, 67.6, 26.9, 26.8, 26.2, 25.1.
,2:5,6-Di-O-isopropylidene-3-O-methoxymethyl-α-D-
glucofuranose (1b). colorless semisolid, 79% (3.16 g); H NMR
500 MHz, CDCl ) δ (ppm): 5.85 (d, 1H, J = 3.5 Hz), 4.71 (s, 2H),
.56 (d, 1H, J = 3.5 Hz), 4.29-4.23 (m, 1H), 4.20 (d, 1H, J = 2.7 Hz),
3
) δ (ppm): 111.8, 109.7, 105.3,
1
,5,6-Tri-O-benzyl-2,3-O-isopropylidene-α-D-manno-furanose
1
3
8
1
(3a). A solution of 2,3-O-isopropylidine-α-D-manno-furanose (0.5
g, 4.5 mmol) (2f) in DMF (5.0 mL), sodium hydride (60 % w/w in
mineral oil, 0.46 g, 22.7 mmol) was added at 0 ºC and stirred at room
temperature for 1 h. Again, the reaction mixture was cooled to the 0
ºC followed by the addition of benzyl bromide (1.4 mL, 22.5 mmol)
and tetra-butyl ammonium iodide (catalytic amount) and stirred at
room temperature for 10 h. The reaction mixture was suspended in
ice cold water (10.0 mL), and extracted with EtOAc (2×10.0 mL).
The combined organic layers were dried over sodium sulfate and
concentrated under vacuum. The remaining crude was purified by
(
4
3
1 2 1 2
4.08 (dd, 2H, J = 3.5 Hz, J = 6.3 Hz), 3.96 (dd, 1H, J = 5.6 Hz, J
=
8.6 Hz), 3.39 (s, 3H), 1.48 (s, 3H), 1.40 (s, 3H), 1.32 (s, 3H), 1.30
1
3
1
(s, 3H); C{ H} NMR (125 MHz, CDCl
3
) δ (ppm): 111.8, 109.1,
1
1
05.2, 95.9, 83.2, 81.0, 78.9, 72.2, 67.5, 55.7, 26.8 (2C), 26.2, 25.3.
39
,2:5,6-Di-O-cyclohexylidene-α-D-glucofuranose (1c). white solid
1
69% (7.0 g); mp 134-137°C, H NMR (500 MHz, CDCl
3
) δ (ppm):
5
4
=
.97 (d, 1H, J = 3.4 Hz), 4.53 (d, 1H, J = 3.4 Hz), 4.36-4.33 (m, 2H),
column chromatography (EtOAc: petroleum ether 15%) to afford 3a
.16 (dd, 1H, J
1
= 6.3 Hz, J
2
= 8.6 Hz), 4.06 (dd, 1H, J
= 5.4 Hz, J = 8.6 Hz), 1.77-1.49 (m,
) δ (ppm): 112.2, 104.3, 84.6,
1.3, 80.2, 64.2, 40.1, 39.9, 39.7, 39.6, 36.3, 35.6, 34.6, 25.0, 24.8,
1 2
= 2.4 Hz, J
1
as a colorless semi solid, 88% (1.81 g). H NMR (500 MHz, CDCl
3
)
8.6 Hz), 3.97 (dd, 1H, J
1
2
13
1
δ (ppm): 7.36-7.24 (m, 15H), 4.95 (d, 1H, J = 11.5 Hz), 4.81 (d, 1H,
J = 11.5 Hz), 4.73 (d, 1H, J = 11.5 Hz), 4.71 (s, 1H), 4.61 (ABq, 2H,
J = 11.5 Hz), 4.54 (d, 1H, J = 11.5 Hz), 4.26 (t, 1H, J = 6.3 Hz), 4.21
2
8
0H); C{ H} NMR (125 MHz, CDCl
3
24.0, 23.7, 23.5.
-O-Acetyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (1d).40
white solid, 70% (2.19 g); mp 61-65 °C; H NMR (500 MHz,
(d, 1H, J = 6.3 Hz), 3.80 (d, 1H, J = 10.3 Hz), 3.72 (dd, 1H, J
Hz, J = 10.3 Hz), 3.66-3.62 (m, 1H), 3.54 (t, 1H, J = 7.6 Hz), 1.55
s, 3H), 1.40 (s, 3H); C{ H} NMR (125 MHz, CDCl
138.4, 138.0, 136.9, 128.5-127.6 (15C), 110.8, 96.0, 79.9, 75.7, 74.5,
1
= 6.3
3
1
2
13
1
(
3
) δ (ppm):
CDCl
H, J = 3.4 Hz), 4.16-4.10 (m, 2H), 3.99 (dd, 1H, J
8.5 Hz), 3.94 (dd, 1H, J = 4.9 Hz, J = 8.5 Hz), 2.03 (s, 3H), 1.43 (s,
H), 1.33 (s, 3H), 1.24 (s, 3H), 1.23 (s, 3H); C{ H} NMR (125
3
) δ (ppm): 5.80 (d, 1H, J = 3.4 Hz), 5.16 (br s, 1H), 4.44 (d,
1
1
= 4.9 Hz, J
2
=
2
5
74.3, 73.5 (2C), 70.2, 70.1, 27.6, 26.2.
[
훼]퐷
+27.0 (c = 0.8, CHCl
: 490.24 (M) , Found:
3
);
1
2
1
3
1
LC-MS (ESI ) m/z Calcd for [C H O ]
+
+
+
3
30 34
6
MHz, CDCl
3
) δ (ppm): 169.4, 112.0, 109.1, 104.9, 83.2, 79.9, 75.5,
490.31; Elemental analysis Anal.Calcd for C30H34O6: C, 73.45; H,
6.99. Found: C, 73.53; H, 7.01.
7
3
2.3, 66.9, 26.7, 26.6, 26.0, 25.1, 20.7.
-O-Benzyl-1,2:5,6-di-O-cyclohexylidene-α-D-glucofuranose
47
3,5,6-Tri-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose (3b).
colorless semisolid, 91% (2.72 g); H NMR (500 MHz, CDCl ) δ
4
1
1
1
(1e). colorless semisolid, 82% (1.87 g); H NMR (500 MHz,
CDCl ) δ (ppm): 7.39-7.31 (m, 5H), 5.90 (d, 1H, J = 3.3 Hz), 4.71
d, 1H, J = 11.5 Hz), 4.69 (d, 1H, J = 11.5 Hz), 4.58 (d, 1H, J = 3.3
Hz), 4.40-4.37 (m, 1H), 4.12 (dd, 2H, J = 4.2 Hz, J = 7.8 Hz), 4.05
= 5.5 Hz, J = 8.7 Hz), 1.58 (m,
0H); C{ H} NMR (125 MHz, CDCl ) δ (ppm): δ 137.7, 128.4
3
(ppm): 7.30-7.23 (m, 15H), 5.91 (d, 1H, J = 3.5 Hz), 4.82 (d, 1H, J
= 11.2 Hz), 4.63 (d, 1H, J = 11.2 Hz), 4.60 (d, 1H, J = 3.5 Hz), 4.58
(s, 2H), 4.48 (d, 2H, J = 11.2 Hz), 4.30 (dd, 1H, J = 3.5 Hz, J = 9.3
1 2
3
(
1
1
1
2
(d, 1H, J = 3.3 Hz), 4.00 (dd, 1H, J
1
2
Hz), 4.13 (d, 1H, J = 3.5 Hz), 4.09-4.04 (m, 1H), 3.91 (d, 1H, J =
10.5 Hz), 3.68 (dd, 1H, J = 5.6 Hz, J = 10.5 Hz), 1.48 (s, 3H), 1.30
13
1
2
3
1
2
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