1H NMR (300 MHz, CDCl3) δ 5.90 (d, J ) 3.6 Hz, 1H), 4.92 (d,
J ) 4.2 Hz, 1H), 4.81 (t, J ) 4.2 Hz, 1H), 4.64 (d, J ) 3.6 Hz,
1H), 4.30 (d, J ) 4.2 Hz, 1H), 4.28-4.20 (m, 2H), 4.14 (q, J )
7.2 Hz, 2H), 3.10 (d, J ) 16.0 Hz, 1H), 2.71 (d, J ) 16.0 Hz, 1H),
1.75-1.60 (br, 1H, exchanges with D2O), 1.47 (s, 3H), 1.33-1.22
(m, 9H); 13C NMR (75 MHz, CDCl3) δ 171.1, 169.0 113.4, 107.9,
85.7, 84.9, 84.5, 83.5, 79.8, 62.8, 61.6, 41.7, 27.6, 26.9, 14.0, 13.9.
Anal. Calcd for C16H24O9: C, 53.30; H, 6.71. Found: C, 53.66;
H, 6.36.
reaction mixture was allowed to attain room temperature. After
4 h, dichloromethane (100 mL) was added. The organic layer on
workup and evaporation of solvent afforded 11 as an anomeric
mixture. Separation by column chromatography (PE/ethyl ac-
etate 8:2) gave R-anomer as thick oil (164 mg; 59% yield); Rf
0.38 (40% EtOAc in hexanes); IR (neat) 1751, 1732 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 6.52 (d, J ) 4.8 Hz, 1H), 5.63 (dd, J
) 4.8 and 2.4 Hz, 1H), 5.41 (d, J ) 5.1 Hz, 1H), 4.98 (t, J ) 5.1
Hz, 1H), 4.92 (dd, J ) 5.1 and 2.4 Hz, 1H), 4.28-420 (dq, J )
7.2 and 3.0 Hz, 2H), 4.13 (q, J ) 7.2 Hz, 2H), 3.14 (d, J ) 16.0
Hz, 1H), 2.79 (d, J ) 16.0 Hz, 1H), 2.10 (s, 3H), 2.06 (s, 3H),
2.03 (s, 3H), 1.31 (t, J ) 7.2 Hz, 3H), 1.22. (t, J ) 7.2 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 169.5, 169.2, 169.1, 169.0, 168.7,
96.4, 85.7, 85.6, 79.6, 77.6, 76.0, 61.8, 60.8, 41.5, 20.7, 20.4, 20.2,
14.0, 13.9. Anal. Calcd for C19H26O12: C, 51.09; H, 5.87. Found:
C, 51.26; H, 5.76. Further elution gave a mixture of R- and
â-anomer (41 mg, 15% yield).
E t h yl 1,7-Did eoxy-6-c-ca r b et h oxy-3,6-a n h yd r o-1-(6-N-
ben zoyl-a m in o-9-H-p u r in -9-yl)-2,5-d ia cetoxy-r-D-glu co-oct-
1,4-fu r a n u r on a te (12). To a stirred solution of 11 (100 mg, 0.23
mmol) in acetonitrile (5 mL) was added bis(trimethylsilyl)-N-
benzoyladenine (130 mg, 0.345 mmol) followed by tert-butyl
dimethylsilyl triflate (0.05 mL, 0.345 mmol) and the reaction
mixture was refluxed. After 3 h, ethyl acetate was added and
the organic layer was washed with a cold solution of NaHCO3
and evaporated. The crude product was purified by column
chromatography (PE/ethyl acetate 5:4) to give 12 as a semisolid
(102 mg, 73% yield); Rf 0.45 (80% EtOAc in hexane); [R]D +77.80
(c 0.65, CHCl3); IR (neat) 3346, 1745, 1610, 1587; 1H NMR (300
MHz, CDCl3) δ 9.05 (br s, 1H), 8.79 (s, 1H), 8.01 (s, 1H), 7.97 (d,
J ) 7.2 Hz, 2H), 7.58 (d, J ) 7.2 Hz, 1H), 7.50 (t, J ) 7.2 Hz,
2H), 6.95 (d, J ) 5.1 Hz, 1H), 5.83 (dd, J ) 5.1 and 1.2 Hz, 1H),
5.58 (d, J ) 5.7 Hz, 1H), 5.45 (dd, J ) 5.7 and 4.5 Hz, 1H), 5.12
(dd, J ) 4.5 and 1.2 Hz, 1H), 4.34 (dq, J ) 6.9 and 2.5 Hz, 2H),
4.17 (q, J ) 6.9 Hz, 2H), 3.21 (d, J ) 16.8 Hz, 1H), 2.92 (d, J )
16.8 Hz, 1H), 2.09 (s, 3H), 2.04 (s, 3H), 1.38 (t, J ) 6.9 Hz, 3H),
1.28 (t, J ) 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 170.9,
169.3, 169.1, 169.0, 168.6, 152.7, 149.2, 142.4, 133.4, 132.7, 128.8
(strong), 127.7 (strong), 122.3, 86.4, 86.0, 85.8, 81.5, 77.3, 77.2,
Eth yl 3,6-An h yd r o-6-(R)-ca r beth oxy-7-d eoxy-1,2-O-iso-
pr opyliden e-5-O-acetoxy-r-D-glu co-oct-1,4-fu r an u r on ate (8).
To a stirred solution of 7 (300 mg, 0.83 mmol) in pyridine (1.3
mL, 15.7 mmol) at 0 °C was added acetic anhydride (0.78 mL,
8.3 mmol) and DMAP (5 mg, 0.04 mmol). The reaction mixture
was allowed to attain room temperature. After 12 h ethyl acetate
(10 mL) was added and the organic layer separated and worked
up. Evaporation of solvent and purification by column chroma-
tography (PE/ethyl acetate 8.5:1.5) afforded 8 as thick oil (314
mg, 94% yield); Rf 0.42 (40% EtOAc in hexanes); [R]D +8.60 (c
0.30, CHCl3); IR (neat) 1747, 1722 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 6.01 (d, J ) 3.5 Hz, 1H), 5.42 (d, J ) 4.4 Hz, 1H), 4.93
(m, 2H), 4.73 (d, J ) 3.7 Hz, 1H), 4.24 (q, J ) 7.2 Hz, 2H), 4.12
(q, J ) 7.2 Hz, 2H), 3.20-2.77 (AB quartet, J ) 16.5 Hz, 2H),
2.12 (s,3H), 1.46 (s, 3H), 1.33 (s, 3H), 1.30 (t, J ) 7.2 Hz, 3H),
1,0.24 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.8,
169.4, 169.2, 112.3, 107.8, 86.2, 84.9, 83.9, 80.9, 77.3, 61.7, 60.9,
42.2, 27.4, 26.8, 20.7, 14.3, 14.2. Anal. Calcd for C18H26O10: C,
53.70; H, 6.51. Found: C, 53.46; H, 6.76.
Eth yl 3,6-An h yd r o-6-(R)-ca r beth oxy-7-d eoxy-1,2-O-iso-
p r op ylid en e-5-O-(S-m eth yld ith ioca r bon a te)-r-D-glu co-oct-
1,4-fu r a n u r on a te (9). To a solution of 7 (100 mg, 0.28 mmol)
in dry THF was added NaH (17 mg, 0.42 mmol) and imidazole
(1 mg, 0.0056 mmol) and the reaction mixture was stirred for 1
h at room temperature. Carbon disulfide (0.13 mL, 2.24 mmol)
was added, the solution was stirred 1 h, and then methyl iodide
(0.03 mL, 0.50 mmol) was added. After an additional 20 min of
stirring dichloromethane (40 mL) was added and the organic
layer was worked up. Purification by column chromatography
(PE/ethyl acetate 9.5:0.5) gave 9 as a thick oil (109 mg, 86%
yield); Rf 0.40 (40% EtOAc in hexanes); [R]D +21.17 (c 0.15,
CHCl3); IR (neat) 1745, 1723 cm-1; 1H NMR (300 MHz, CDCl3)
δ 6.30 (d, J ) 4.5 Hz, 1H), 6.03 (d, J ) 4.2 Hz, 1H), 5.08 (t, J )
4.2, 3.9 Hz, 1H), 4.96 (d, J ) 3.9 Hz, 1H), 4.78 (d, J ) 4.5 Hz,
1H), 4.24 (q, J ) 7.2 Hz, 2H), 4.14 (q, J ) 7.2 Hz, 2H), 3.18 (d,
J ) 16.2 Hz, 1H), 2.83 (d, J ) 16.2 Hz, 1H), 2.57 (s, 3H), 1.46 (s,
3H), 1.33-1.22 (m, 9H); 13C NMR (75 MHz, CDCl3) δ 215.1,
169.2, 169.1, 112.4, 108.1, 86.9, 86.3, 83.9, 83.4, 83.2, 61.8, 60.9,
41.8, 27.4, 27.1, 26.8, 14.2, 13.9. Anal. Calcd for C18H26S2O9: C,
46.54; H, 5.97. Found: C, 46.26; H, 5.56.
Eth yl 3,6-An h yd r o-6-(R)-ca r beth oxy-7,5-d id eoxy-1,2-O-
isop r op ylid en e-r-D-glu co-oct-1,4-fu r a n u r on a te (10). A solu-
tion of 9 (100 mg, 0.22 mmol) in dry toluene (5 mL) was added
to a refluxing solution of tributyltin hydride (69 mg, 0.48 mmol)
and AIBN (2 mg, 0.011 mmol) in toluene under N2. The solution
was refluxed for 4 h, toluene was evaporated, and residue was
dissolved in ethyl acetate (30 mL). Workup and purification by
column chromatography (PE/ethyl acetate 8.5:1.5) afforded 10
as a thick oil (52 mg, 69% yield); Rf 0.38 (40% EtOAc in hexanes);
[R]D +15.60 (c 0.65, CHCl3); IR (neat) 1742 1729 cm-1; 1H NMR
(300 MHz, CDCl3) δ 5.78 (d, J ) 3.9 Hz, 1H), 4.92-4.88 (m, 2H),
4.63 (d, J ) 3.9 Hz, 1H), 4.28-4.08 (m, 4H), 2.97 (d, J ) 15.3
Hz, 1H), 2.68 (d, J ) 14.1 Hz, 1H), 2.64 (d, J ) 15.3 Hz, 1H),
2.22 (dd, J ) 14.1, 4.2 Hz, 1H), 1.45 (s, 3H), 1.30 (s, 3H), 1.28 (t,
J ) 7.2 Hz, 3H), 1.25 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 172.4, 168.9, 111.5, 106.9, 89.0, 84.8, 84.5, 82.8, 61.4,
60.8, 42.8, 42.3, 27.2, 26.6,14.2 (strong). Anal. Calcd for
C16H24O8: C, 55.78; H, 7.02. Found: C, 55.96; H, 6.76.
62.2, 61.1, 41.5, 20.6, 20.2, 14.3, 14.2. Anal. Calcd for C29H31
N5O11: C, 55.65; H, 4.99. Found: C, 55.76; H, 4.76.
-
1,7-Did eoxy-6-c-ca r boxy-3,6-a n h yd r o-1-(6-a m in o-9-H-p u -
r in -9-yl)-r-D-glu co-oct-1,4-fu r a n u r on ic Acid (1e). A solution
of 12 (100 mg, 0.16 mmol) in ethanol-water (7:3, 2 mL) and
NaOH (51 mg, 1.28 mmol) was stirred at room temperature.
After 24 h, the reaction mixture was neutralized with 1 N HCl
and the volume of the reaction mixture was reduced to half by
evaporation at reduced pressure. The solution was loaded on a
Chromabond C18 ec (Macherey-Nagel) column and eluted first
with water to remove all inorganic salt and then with 10%
acetone in water. Evaporation of solvent gave a semisolid that
was repeatedly washed with chloroform (3 × 2 mL) to give 1e
as a solid (38 mg, 63% yield); mp 232-235 °C; [R]D +32.30 (c
0.15, CH3OH); IR (KBr) 3442, 1737, 1627 cm-1 1H NMR (300
;
MHz, D2O) δ 8.30 (s, 1H), 7.92 (s, 1H), 5.85 (d, J ) 6.0 Hz, 1H),
4.83 (m, 2H), 4.22 (d, J ) 5.1 Hz, 1H), 3.52 (s, 1H), 2.66-2.44.
(AB quartet, J ) 15.3 Hz, 2H); 13C NMR (75 MHz, D2O) δ 172.3,
172.2, 155.2, 152.4, 149.0, 140.8, 118.8, 89.6, 86.3, 81.7, 79.5,
76.0, 75.1, 42.6. Anal. Calcd for C14H15N5O8: C, 44.08; H, 3.96.
Found: C, 44.32; H, 3.77.
Ack n ow led gm en t. We thank the Department of
Science and Technology (SP/S1/G-23/2000) and the
University Grants Commission for financial support and
for procuring the high field NMR facility.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra of all new compounds 2-12 and 1e. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Eth yl 3,6-An h yd r o-6-(R)-ca r beth oxy-7-d eoxy-1,2,5-O-tr i-
a cetoxy-r- a n d â-D-glu co-oct-1,4-fu r a n u r on a te (11). To a
stirred solution of compound 8 (250 mg, 0.62 mmol) in dichlo-
rometane (20 mL) at 0 °C was added a mixture of acetic acid
and acetic anhydride (1:1.5, 20 mL) and H2SO4 (0.01 mL). The
J O026858J
4534 J . Org. Chem., Vol. 68, No. 11, 2003