G. V. M. Sharma et al. / Tetrahedron: Asymmetry 16 (2005) 1135–1140
1139
room temperature for 3 h. MeOH was evaporated,
diluted with water (10 mL), extracted with CH2Cl2
(3 · 10 mL) and dried over Na2SO4. Evaporation of
solvent and purification of residue by column chroma-
tography (silica gel, 40% EtOAc in hexane) afforded 14
(5 mL) and stirred at 80 ꢁC for 5 h. Work-up and puri-
fication (silica gel, 5% EtOAc in hexane) as described
for 11 gave 17 (1.5 g) in 53% yield as a pale syrup. IR
(neat): 2984, 1585, 1180, 1015, 835 cmꢀ1; [a]D = ꢀ11.25
(c 1, CHCl3); 1H NMR (CDCl3, 200 MHz): d 1.40,
1.47, 1.56 (3s, 12H), 3.98–4.15 (m, 5H, H-1, 3, 7),
4.30–4.41 (m, 2H, H-2, 6), 4.81–4.95 (m, 2H, H-4, 5),
6.75–6.84 (m, 2H, Ar–H), 6.9–7.05 (m, 2H, Ar–H);
FABMS m/z (relative intensity in %): 369 (M+ + H,
40), 311(30), 185 (26), 125 (100), 101 (100).
(0.218 g) in 66% yield as
a pale yellow syrup.
[a]D = +65.5 (c 1.0, CHCl3); 1H NMR (CDCl3, 200
MHz): d 1.32, 1.46 (2s, 6H), 2.48–2.60 (m, 2H, H-8),
3.55–3.85 (m, 2H, H-9), 4.05–4.42 (m, 3H, H-1, 2),
4.72–4.90 (m, 3H, H-3, 4, 5), 5.31–5.52 (br s, 2H,
NH2), 6.80–7.05 (m, 4H, Ar–H); FABMS m/z (relative
intensity %): 395 (M+ + H, 5), 279 (7), 176 (5), 154
(13), 54 (14). HRMS: Calculated for C19H24FN2O6:
395.161840; found: 395.159948.
4.12. 3,6-Anhydro-4,5-O-isopropylidene-7-(4-fluorophen-
yl)-D-glycero-D-mannoheptitol 18
A solution of 17 (1.11 g, 3.01 mmol) in aq MeOH (5:1,
10 mL) was treated with concd HCl (0.2 mL) at 0 ꢁC and
stirred at room temperature for 4 h. Work-up and purifica-
tion (silica gel, 50% EtOAc in hexane) as described for 7
afforded 18 (0.71 g) in 72% yield as a pale yellow syrup.
4.9. (2R,3S,4S,5R)-trans-3,4-Dihydroxy-5-(4-fluorophen-
oxymethyl)-2-(1-N-hydroxyureidyl-3-butyn-4-yl)tetrahy-
drofuran 2
To a cooled (0 ꢁC) and stirred solution of 14 (0.05 g,
0.126 mmol) in MeOH (9 mL) catalytic concd HCl (1
drop) was added followed by water (1 mL) and stirred
at room temperature for 24 h. Solid NaHCO3 was added
to neutralize the reaction mixture and solvent evapo-
rated. It was filtered and washed with ethyl acetate
(2 · 10 mL). The combined organic layers were dried
over Na2SO4, concentrated and purified by column chro-
matography (silica gel, EtOAc) to afford 2 (0.035 g) in
IR (neat): 3241, 3010, 1572, 1150, 1030, 900 cmꢀ1
;
[a]D = ꢀ11.33 (c 0.7, CHCl3); 1H NMR (CDCl3,
200 MHz): d 1.3, 1.55 (2s, 6H), 2.0 (br s, 2H, OH), 3.6–
3.85 (m, 2H, 7), 3.92 (m, 1H, H-3), 4.0 (d, 2H,
J = 4.54 Hz, H-1), 4.05–4.1 (m, 1H, H-2), 4.32–4.4 (m,
1H, H-6), 4.85–5.0 (m, 2H, H-4, 5), 6.73–6.85 (m, 2H, Ar–
H), 6.9–7.05 (m, 2H, Ar–H); FABMS m/z (relative intensity
in %): 329 (M+ + H, 8), 271(6), 109 (22), 69 (54), 57 (100).
1
78% yield as a syrup. [a]D = +14.2 (c 1.0, CHCl3); H
4.13. (2R,5R) 5-(1,10-Dibromoethylen-2-yl)–2-(4-fluoro-
phenoxymethyl)-3,4-O-isopropylidene tetrahydrofuran 20
NMR (DMSO, 200 MHz): d 2.30–2.48 (m, 2H, H-20),
3.80–4.15 (m, 4H, H-1), 4.18–4.31 (m, 2H, H-3, 4),
5.01–5.12 (m, 3H, H-5), 5.30 (d, 1H, J = 4.88 Hz, H-2),
6.30 (s, 2H, NH2), 6.80–6.99 and 7.0–7.19 (2m, 4H,
Ar–H), 9.38 (s, 1H, N–OH); FABMS m/z (relative inten-
sity in %): 355 (M+ + H, 7), 339 (5), 281 (9.5), 221 (12.9),
109 (100). Anal. Calcd for C16H19FN2O6: C, 54.24; H,
5.40. Found: C, 54.21; H, 5.38.
A solution of 18 (0.74 g, 2.25 mmol) in CH2Cl2 (10 mL)
containingsaturated NaHCO
solution (1.2 mL)
3
was treated with NaIO4 (0.48 g, 2.25 mmol) portionwise
at 0 ꢁC and stirred at room temperature for 5 h. Work-
up and purification as described for 8 afforded 2,3-
O-isopropylidene-5-(4-fluorophenyl)-D-glycero-D-lyxo-
pentanedialdo-1,4-furanoside 19 (0.53 g) in 79% yield as
a pale yellow syrup, which was used as such for further
reaction immediately.
4.10. 3,6-Anhydro-1,2:4,5-di-O-isopropylidene-7-(p-tolu-
enesulfonyl)-D-glycero-D-mannoheptitol 16
A solution of 15 (3.68 g, 13.4 mmol) and Et3N (5.6 mL,
40.29 mmol) in CH2Cl2 (40 mL) at 0 ꢁC, was treated with
p-TsCl (3.83 g, 20.14 mmol) and stirred at room temper-
ature for 8 h. Work-up and purification (silica gel, 15%
EtOAc in hexane) as described for 10 afforded 16
(3.3 g) in 57% yield as a pale yellow syrup. IR (neat):
2950, 1580, 1210, 1175, 1005, 825 cmꢀ1; [a]D = +9.7 (c
A solution of Ph3P (2.32 g, 8.8 mmol) in CH2Cl2 (5 mL)
was treated with a solution of CBr4 (1.03 g, 4.4 mmol) in
CH2Cl2 (5 mL) at 0 ꢁC dropwise. After 15 min, a solu-
tion of 19 (0.53 g, 1.77 mmol) in CH2Cl2 (5 mL) was
added and stirred at the same temperature for 30 min.
The solvent was evaporated and the residue subjected
to column chromatography (silica gel, 15% EtOAc in
hexane) to afford 20 (0.69 g) in 89% yield as a pale yellow
1
1.0, CHCl3); H NMR (CDCl3, 200 MHz): d 1.27, 1.31,
1.37, 1.43 (4s, 12H), 2.48 (s, 3H), 3.75–3.88 (m, 2H, H-
7), 3.90–4.10 (m, 3H, H-1, 3), 4.10–4.19 (m, 1H, H-6),
4.20–4.31 (m, 1H, H-2), 4.60–4.80 (m, 2H, H-4, 5), 7.33
(d, J = 8.7 Hz, 2H, Ar–H), 7.75 (d, J = 8.7 Hz, 2H, Ar–
H); FABMS m/z (relative intensity in %): 429 (M+ + H,
38), 371 (12), 155 (30), 91 (46), 57 (100).
syrup. IR (neat): 2995, 1590, 1410, 1130, 890 cmꢀ1
;
[a]D = ꢀ80 (c 0.5, CHCl3); 1H NMR (CDCl3,
300 MHz): d 1.34, 1.51 (2s, 6H), 3.91–4.11 (m, 2H),
4.29–4.35 (m, 1H), 4.74–4.91 (m, 3H, H-3, 4, 5), 6.58
(d, 1H, J = 7.5 Hz, H-6), 6.78–6.82 (m, 2H, Ar–H),
6.90–6.97 (m, 2H, Ar–H); FABMS m/z (relative intensity
in %): 453 (M+ + H, 12), 147 (12), 125 (16), 95 (44), 81
(50), 69 (62), 59 (100).
4.11. 3,6-Anhydro-1,2:4,5-di-O-isopropylidene-7-(4-fluoro-
phenyl)-D-glycero-D-mannoheptitol 17
4.14. (2R,3S,4S,5R)-trans-5-Ethynyl-2-(4-fluorophen-
oxymethyl)-3,4-O-isopropylidene tetrahydrofuran 3
A solution of 4-fluorophenol (0.95 g, 8.44 mmol) in
DMF (2 mL) was added to a suspension of NaH
(0.611 g, 25.4 mmol) in DMF (3 mL) at 0 ꢁC and then
treated with a solution of 16 (3.3 g, 7.7 mmol) in DMF
A solution of 20 (0.65 g, 1.47 mmol) in THF (5 mL) was
cooled to ꢀ78 ꢁC and treated with n-BuLi (1.7 mL,