2106 J . Org. Chem., Vol. 63, No. 7, 1998
Francisco et al.
) 3.7 Hz), 7.31-7.37 (5H, m); 13C NMR 58.4 (q), 60.4 (q), 60.7
(q), 61.5 (t), 69.1 (t), 70.8 (d), 79.3 (d), 81.6 (d), 83.0 (d), 94.9
(d), 127.7 (d), 128.0 (2 × d), 128.2 (2 × d), 136.9 (s); MS m/z
(rel intensity) 313 (M+ + 1, 2), 295 (11), 263 (22), 231 (8), 205
(50), 203 (5), 189 (13), 187 (5), 157 (84). Anal. Calcd for
C16H24O6: C, 61.51; H, 7.75. Found: C, 61.28; H, 7.80.
â-Anomer 21â: syrup; [R]D -35.5° (c ) 0.166); IR3606, 3474
(d), 85.1 (d), 105.2 (d), 109.1 (s), 112.4 (s), 113.8 (2 × d), 129.2
(s), 129.6 (2 × d), 159.3 (s); MS (EI, 30 eV) m/z (rel intensity)
380 (M+, 3), 365 (17), 322 (3), 259 (44), 243 (1), 201 (71), 185
(6), 143 (64), 127 (4). Anal. Calcd for C20H28O7: C, 63.14; H,
7.42. Found: C, 63.02; H, 7.71.
p -Met h oxyb en zyl 2,3-O-Isop r op ylid en e-r-D-m a n n o-
fu r a n osid e (25). Compound 24 (5.5 g, 14.47 mmol) was
dissolved in 70% AcOH (40 mL), and the mixture was stirred
at room temperature for 18 h, poured into water, and extracted
with diethyl ether. The organic layer was washed with
NaHCO3 until no acidic reaction was observed. It was then
dried and concentrated, and the residue was purified by silica
gel flash chromatography (hexanes-EtOAc, 1:1) to give 25
(4.57 g, 13.44 mmol, 93%) as a noncrystalline solid: [R]D +81°
1
cm-1; H NMR (500 Hz) 3.06 (1H, dd, J ) 7.8, 8.5 Hz), 3.17
(1H, dd, J ) 8.5, 7.5 Hz), 3.21-3.23 (1H, m), 3.55 (3H, s), 3.61
(3H, s), 3.63 (3H, s), 3.70-3.74 (2H, m), 3.88 (1H, m), 4.41 (1H,
d, J ) 7.8 Hz), 4.69 (1H, d, J ) 12.0 Hz), 4.88 (1H, d, J ) 12.0
Hz), 7.31-7.37 (5H, m); 13C NMR 60.2 (q), 60.3 (q), 60.6 (q),
61.5 (t), 71.0 (t), 74.9 (d), 79.1 (d), 83.6 (d), 86.1 (d), 102.3 (d),
127.4 (2 × d), 127.6 (d), 128.2 (2 × d), 137.2 (s); MS m/z (rel
intensity) 313 (M+ + 1, 2), 295 (21), 263 (63), 231 (10), 205
(83), 189 (29), 187 (8), 173 (100), 157 (91). Anal. Calcd for
(c ) 0.406); IR 3601, 3475 cm-1 1H NMR 1.32 (3H, s), 1.47
;
(3H, s), 3.70 (1H, dd, J ) 5.4, 11.2 Hz), 3.80 (3H, s), 3.87 (1H,
dd, J ) 2.9, 11.2 Hz), 3.94-4.04 (2H, m), 4.42 (1H, d, J ) 11.5
Hz), 4.57 (1H, d, J ) 11.5 Hz), 4.63 (1H, d, J ) 5.9 Hz), 4.85
(1H, dd, J ) 3.4, 5.9 Hz), 5.09 (1H, s), 6.87 (2H, m), 7.24 (2H,
m); 13C NMR 24.5 (q), 25.8 (q), 55.2 (q), 64.3 (t), 68.6 (t), 70.1
(d), 79.1 (d), 80.0 (d), 84.7 (d), 105.0 (d), 112.5 (s), 113.8 (2 ×
d), 129.2 (s), 129.7 (2 × d), 159.2 (s); MS (EI, 30 eV) m/z (rel
intensity) 340 (M+, 11), 325 (6), 282 (2), 219 (1), 203 (1), 161
(100), 145 (10), 143 (34). Anal. Calcd for C17H24O7: C, 59.97;
H, 7.11. Found: C, 59.66; H, 7.40.
C
16H24O6: C, 61.51; H, 7.75. Found: C, 61.59; H, 7.85.
Ben zyl 2,3,4-Tr i-O-m eth yl-D-glu copyr an osidu r on ic Acid
(22). Following the procedure described for 8, compound 21R
(375 mg, 1.2 mmol) afforded, after purification by silica gel
flash chromatography (hexanes-EtOAc, 1:1), acid 22R (348
mg, 89%) as a syrup: [R]D +114.8° (c ) 0.196); IR 3428, 1728,
1
1608 cm-1; H NMR 3.26 (1H, dd, J ) 3.6, 9.3 Hz), 3.39 (1H,
dd, J ) 8.9, 10 Hz), 3.41 (3H, s), 3.57 (3H, s), 3.64 (3H, s),
3.62 (1H, dd, J ) 9.3, 8.9 Hz), 4.16 (1H, d, J ) 10 Hz), 4.62
(1H, d, J ) 12.1 Hz), 4.78 (1H, d, J ) 12.1 Hz), 5.05 (1H, d, J
) 3.6 Hz), 7.32-7.40 (5H, m); 13C NMR 58.6 (q), 60.5 (q), 60.9
(q), 69.5 (t), 69.7 (d), 81.0 (d), 81.0 (d), 82.7 (d), 95.2 (d), 128.0
(d), 128.3 (2 × d), 128.4 (2 × d), 136.4 (s), 173.4 (s); MS m/z
(rel intensity) 327 (M+ + 1, 1), 309 (1), 277 (4), 219 (1), 187
(6), 187 (5), 157 (17), 155 (5), 143 (10). Anal. Calcd for
p-Meth oxyben zyl 6-O-(ter t-Bu tyld im eth ylsilyl)-2,3-O-
isop r op ylid en e-r-D-m a n n ofu r a n osid e (26). Following the
procedure described for 12, compound 25 (3 g, 8.82 mmol)
afforded 26 (3.44 g, 86%) as a syrup: [R]D +70.8° (c ) 0.212);
IR 3567 cm-1; 1H NMR 0.00 (6H, s), 0.81 (9H, s), 1.21 (3H, s),
1.36 (3H, s), 3.60-3.75 (2H, m), 3.69 (3H, s), 3.87 (2H, m), 4.28
(1H, d, J ) 11.3 Hz), 4.47 (1H, d, J ) 11.3 Hz), 4.52 (1H, d, J
) 5.8 Hz), 4.75 (1H, dd, J ) 5.8, 3.1 Hz), 4.95 (1H, s), 6.76
(2H, m), 7.13 (2H, m); 13C NMR -0.1 (q), 0.0 (q), 18.21 (s),
24.5 (q), 25.8 (3 × q), 25.9 (q), 55.1 (q), 64.4 (t), 68.5 (t), 69.5
(d), 78.8 (d), 80.1 (d), 84.9 (d), 105.2 (d), 112.3 (s), 113.7 (2 ×
d), 129.3 (s), 129.6 (2 × d), 159.2 (s); MS (EI, 30 eV) m/z (rel
intensity) 439 (M+ - Me, 15), 317 (4), 276 (4), 275 (18), 259
(1), 241 (22). Anal. Calcd for C23H38O7Si: C, 60.76; H, 8.42.
Found: C, 60.51; H, 8.52.
C
16H22O7: C, 58.88; H, 6.79. Found: C, 58.93; H, 6.67.
Analogously, compound 21â yielded anomer 22â (93%) as a
1
syrup: [R]D -54.6° (c ) 0.24); H NMR 3.18 (1H, dd, J ) 7.0,
7.5 Hz), 3.23 (1H, dd, J ) 8.4, 9 Hz), 3.48 (1H, dd, J ) 7.5, 9
Hz), 3.57 (3H, s), 3.59 (3H, s), 3.61 (3H, s), 3.86 (1H, d, J )
8.4 Hz), 4.49 (1H, d, J ) 7.0 Hz), 4.65 (1H, d, J ) 12.0 Hz),
4.94 (1H, d, J ) 12.0 Hz), 7.31-7.37 (5H, m); 13C NMR 60.3 (2
× q), 60.5 (q), 71.4 (t), 81.3 (d), 83.2 (d), 85.5 (2 × d), 102.4 (d),
127.7 (d), 128.3 (4 × d), 137.2 (s), 174.6 (s). Anal. Calcd for
C
16H22O7: C, 58.88; H, 6.79. Found: C, 58.61; H, 6.92.
p-Meth oxyben zyl 5-O-Ben zyl-6-O-ter t-(bu tyld im eth yl-
silyl)-2,3-O-isop r op ylid en e-r-D-m a n n ofu r a n osid e (27). To
a suspension of NaH (132 mg, 5.5 mmol) in DMF (10 mL) was
added, at 0 °C under Ar, the product 26 (890 mg, 1.96 mmol)
dissolved in DMF (2 mL). When the hydrogen evolution
ceased, benzyl bromide (0.3 mL, 2.53 mmol) was added at 0
°C, and the mixture was stirred at room temperature for 10
h. Then MeOH was added to quench the excess of NaH, and
the resulting mixture poured into water and extracted with
diethyl ether. Silica gel flash chromatography of the residue
(hexanes-EtOAc, 80:20) gave 27 (840 mg, 79%) as a syrup:
[R]D +46.3° (c ) 0.356); 1H NMR 0.13 (6H, s), 0.95 (9H, s),
1.34 (3, s), 1.47 (3H, s), 3.75 (1H, dd, J ) 5.6, 10.6 Hz), 3.81
(3H, s), 3.85 (1H, ddd, J ) 1.7, 5.6, 9.0 Hz), 3.97 (1H, dd, J )
1.7, 10.6 Hz), 4.05 (1H, dd, J ) 9.0, 3.4 Hz), 4.40 (1H, d, J )
11.4 Hz), 4.59 (1H, d, J ) 11.4 Hz), 4.62 (1H, d, J ) 5.6 Hz),
4.70 (1H, d, J ) 11.1 Hz), 4.84 (1H, d, J ) 11.1 Hz), 4.85 (1H,
dd, J ) 5.6, 3.4 Hz), 5.06 (1H, s), 6.88 (2H, m), 7.22-7.39 (7H,
m); 13C NMR -5.4 (q), -5.3 (q), 18.3 (s), 24.9 (q), 25.9 (3 × q),
26.1 (q), 55.2 (q), 64.2 (t), 68.4 (t), 73.3 (t), 77.8 (d), 78.4 (d),
80.0 (d), 84.7 (d), 105.3 (d), 112.0 (s), 113.8 (2 × d), 127.3 (d),
128.0 (2 × d), 128.1 (2 × d), 129.5 (s), 129.6 (2 × d), 139.0 (s),
159.2 (s); MS (EI, 30 eV) m/z (rel intensity) 529 (M+ - Me, 4),
423 (2), 365 (7), 381 (2), 259 (5). Anal. Calcd for C30H44O7Si:
C, 66.14; H, 8.14. Found: C, 66.10; H, 8.27.
2,3,4-Tr i-O-m eth yl-D-glu cop yr a n u r on ic Acid (23). Fol-
lowing the procedure described for 9, acid 22 (125 mg, 0.38
mmol) in MeOH (10 mL) afforded the title compound 23 (75
mg, 0.32 mmol, 83%) as a syrup: IR (CHCl3) 3688, 3398, 1730
1
cm-1; H NMR (DMSO-d6, 200 Hz) 2.78 (1H, dd, J ) 7.7, 8.7
Hz), 3.07-3.23 (5H, m), 3.32 (3H, s), 3.36 (3H, s), 3.37 (3H, s),
3.43 (3H, s), 3.44 (3H, s), 3.48 (3H, s), 3.57 (1H, d, J ) 9.0
Hz), 3.96 (1H, d, J ) 7.7 Hz), 5.17 (1H, bs); 13C NMR (DMSO-
d6) 57.0 (2 × q), 59.1 (q), 59.3 (2 × q), 59.6 (q), 69.1 (d), 73.3
(d), 80.5 (d), 80.6 (d), 80.7 (d), 81.6 (d), 83.9 (d), 84.4 (d), 89.6
(d), 96.4 (d), 170.1 (s), 170.9 (s); MS m/z (rel intensity) 218
(M+ - H2O), 186 (1), 161 (42), 159 (1), 145 (3), 129 (3), 113 (7).
Anal. Calcd for C9H16O7: C, 45.76; H, 6.83. Found: C, 45.83;
H, 6.91.
p-Meth oxyben zyl 2,3:5,6-Di-O-isop r op ylid en e-r-D-m a n -
n ofu r a n osid e (24). To a suspension of NaH (1.3 g, 27 mmol)
in DMF (25 mL) was added, under Ar at 0 °C, 2,3:5,6-di-O-
isopropylidene-D-mannofuranose (5 g, 19.2 mmol) dissolved in
DMF (5 mL). When the hydrogen evolution ceased, p-
methoxybenzyl chloride (3.9 mL, 28.8 mmol) was added at 0
°C, and the reaction was stirred at room temperature for 24
h. Then MeOH was added to eliminate the excess of NaH,
and the resulting mixture was poured into water and extracted
with ethyl acetate. The combined extracts were dried over
Na2SO4, concentrated at reduced pressure, and the crude
purified by silica gel flash chromatography (hexanes-EtOAc,
1:1) to yield compound 24 (6 g, 82%) as a syrup: [R]D +74.3°
(c ) 0.23); 1H NMR 1.32 (3H, s), 1.40 (3H, s), 1.47 (6H, s),
3.81 (3H, s), 3.98 (1H, dd, J ) 3.5, 7.8 Hz), 4.03 (1H, dd, J )
4.5, 8.7 Hz), 4.14 (1H, dd, J ) 6.1, 8.7 Hz), 4.39-4.47 (1H, m),
4.42 (1H, d, J ) 11.2 Hz), 4.59 (1H, d, J ) 11.2 Hz), 4.64 (1H,
d, J ) 5.6 Hz), 4.82 (1H, dd, J ) 3.5, 5.8 Hz), 5.06 (1H, s),
6.89 (2H, m), 7.26 (2H, m); 13C NMR 24.4 (q), 25.1 (q), 25.8
(q), 26.8 (q), 55.2 (q), 66.9 (t), 68.6 (t), 73.0 (d), 79.5 (d), 80.3
p-Meth oxyben zyl 5-O-Ben zyl-2,3-O-isop r op ylid en e-r-
D-m a n n ofu r a n osid e (29). To a solution of 27 (716 mg, 1.3
mmol) in MeOH (15 mL) was added at 0 °C NH4F (400 mg,
10.8 mmol), and the reaction was stirred at room temperature
for 20 h, poured into water, and extracted with EtOAc. Silica
gel flash chromatography of the residue (gradient hexanes-
EtOAc, 8:2 f 1:1) gave 29 (514 mg, 1.19 mmol, 91%) as a
1
syrup: [R]D +70.5° (c ) 0.312); IR 3586 cm-1; H NMR 1.34
(3H, s), 1.47 (3H, s), 3.80 (3H, s), 3.77-3.94 (3H, m), 4.12 (1H,
dd, J ) 8.2, 3.4 Hz), 4.41 (1H, d, J ) 11.4 Hz), 4.59 (1H, d, J