C-Glycoside of a Novel Sialyl Lewis X Mimetic
J . Org. Chem., Vol. 65, No. 8, 2000 2547
tetr a -O-ben zyl-R-D-m a n n op yr a n osid e 5. Enol ether 9 (3.6
g, 3.4 mmol), 2,6-di-tert-butyl-4-methylpyridine (6.3 g, 40
mmol), and freshly activated, powdered 4A molecular sieves
(1.0 g) in anhydrous CH2Cl2 (100 mL) were stirred for 15 min
at room temperature under an argon atmosphere and then
cooled to 0 °C. Methyl triflate (3.7 mL, 33 mmol) was then
introduced, and the mixture was warmed to room temperature
and stirred for an additional 18 h, at which time triethylamine
(5 mL) was added. The mixture was diluted with ether, washed
with saturated aqueous NaHCO3 and brine, dried (Na2SO4),
filtered, and evaporated under reduced pressure. Flash chro-
matography of the residue on basic alumina (Brockmann I,
150 mesh) provided 5 (2.8 g, 88%): clear oil; Rf 0.55 (15%
EtOAc/petroleum ether); [R]D 17.6 (c 1.28, CHCl3); IR (neat)
1689, 1682 cm-1; 1H NMR (400 MHz, C6D6) δ 1.18 (s, 9H), 1.35,
1.54 (both s, 3H ea), 2.25 (m, 2H), 3.73 (dd, J ) 2.9, 4.0 Hz,
1H), 3.80 (dd, J ) 2.9, 7.7 Hz, 1H), 3.9 (m, 4H), 4.14 (m, 2H),
4.21 (t, J ) 7.3 Hz, 1H), 4.29 (d, J ) 6.2 Hz, 1H), 4.42-4.58
(m, 9H), 4.64 (d, J ) 2.6 Hz, 1H), 4.74 (apparent d, J ) 12 Hz,
1H), 7.00-7.40 (m, 26H), 7.70 (m, 4H); 13CNMR (75 MHz,
CDCl3) δ 19.5, 27.0, 28.6, 35.0, 63.0, 69.6, 69.7, 71.4, 71.6, 71.7,
72.1, 73.6, 74.0, 74.4, 75.1, 75.4, 75.7, 77.9, 100.0, 110.2, 127.6,
127.7, 127.8, 127.9, 128.0, 128.2, 128.4, 128.5, 130.0, 135.7,
135.8, 138.5, 138.6, 152.5; FABHRMS calcd for C60H69O9Si (M
+ H) 961.4711, found 961.4708.
d, J ) 14 Hz, 1H), 2.20 (m, partially hidden under br s at δ
2.24, 1H), 2.24 (br s, 1H, D2O ex), 2.52 (br s, 1H, D2O ex), 3.17
(m, 1H), 3.31 (br d, J ) 9.2 Hz, 1H), 3.46 (t, J ) 5.5 Hz, 1H),
3.50 (br s, 1H), 3.65 (m, 3H), 3.72-3.98 (m, 5H), 4.10 (m, 2H,
D2O ex 1H), 4.40-4.70 (m, 8H), 4.80 (apparent d, J ) 11 Hz,
1H), 7.15-7.55 (m, 26H), 7.70 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ 20.0, 27.5, 27.6, 29.9, 61.1, 64.1, 69.7, 69.9, 70.6, 70.7,
70.8, 71.0, 72.5, 72.6, 72.7, 72.8, 73.0, 73.3, 73.4, 74.4, 75.0,
75.7, 75.9, 76.1, 76.3, 76.5, 76.6, 78.2, 78.5, 78.9, 79.2, 128.2,
128.3, 128.5, 128.6, 128.7, 128.9, 129.1, 129.1, 129.3, 129.4,
129.5, 130.3, 133.9, 134.2, 136.2, 136.3, 136.6, 136.7, 138.0,
138.8; ESMS 961.5 (M + Na).
3-O-Ca r boxym eth yl-6-O-ter t-bu tyld ip h en ylsilyl-â-D-ga -
la ctop yr a n osyl 1-Ca r ba -2,3.4,6-tetr a -O-ben zyl-r-D-m a n -
n op yr a n osid e 17. A mixture of triol 16 (130 mg, 0.14 mmol),
dibutyltin oxide (32 mg, 0.14 mmol), and anhydrous toluene
(5 mL) was heated at reflux in a Dean-Stark apparatus for 1
h. The solvent was evaporated in vacuo, and the residue was
dissolved in dry toluene (3 mL). n-Bu4NI (40 mg, 0.14 mmol)
and methyl 2-bromoacetate (0.1 mL, 0.42 mmol) were added,
and the solution was heated at reflux for 1 h, at which time
the volatiles were removed under reduced pressure to give a
brown syrup. Partial purification of this material by flash
chromatography provided an approximately 1:1 mixture (100
mg) of two components, Rf 0.45 and 0.35 (30% EtOAc/
petroleum ether).
3,4-O-Isop r op lylid en e-6-O-ter t-bu tyld ip h en ylsilyl-â-D-
galactopyr an osyl 1-Car ba-2,3.4,6-tetr a-O-ben zyl-r-D-m an -
n op yr a n osid e 4. BH3‚Me2S (10 mL of a 1 M solution in
CH2Cl2, 10 mmol) was added at 0 °C to a solution of glycal 5
(2.3 g, 2.5 mmol) in anhydrous THF (50 mL) under an
atmosphere of argon. The mixture was warmed to room
temperature and stirred for an additional 1 h at this temper-
ature. At that time the solution was recooled to 0 °C and
treated with a mixture of 3 N NaOH (10 mL) and 30% aqueous
H2O2 (10 mL) for 30 min. The mixture was then diluted with
ether and washed with saturated aqueous NaHCO3 and brine.
The organic extract was dried (Na2SO4), filtered, and evapo-
rated under reduced pressure. Flash chromatography of the
residue provided 4 (2.0 g, 83%): white solid; Rf 0.30 (15%
EtOAc/petroleum ether); [R]D 22.9 (c 2.10, CHCl3); IR (neat)
3391 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.10 (s, 9H), 1.41 (s,
3H), 1.56 (m, buried under s at δ1.58), 1.58 (s, 3H), 2.22 (m,
1H), 3.19 (m, 1H), 3.56 (m, 2H), 3.64-4.22 (m, 9H), 4.12 (d, J
) 5.5 Hz, 1H, D2O ex), 4.36 (d, J ) 5.5 Hz, 1H), 4.42-4.84 (m,
9H), 7.10-7.85 (m, 30H); 13C NMR (75 MHz, CDCl3) δ 20.1,
27.3, 27.6, 29.3, 30.4, 63.7, 70.2, 70.5, 72.2, 72.5, 72.9, 73.6,
74.1, 74.6, 74.9, 76.1, 76.9, 77.6, 77.8, 78.9, 80.7, 109.9, 128.2,
128.3, 128.4, 128.5, 128.6, 128.8, 128.9, 129.1, 130.3, 134.2,
134.4, 136.3, 136.4, 138.3, 138.8, 138.9; FABHRMS calcd for
The mixture obtained in the previous step was treated with
a 1:1 mixture of aqueous 3 N NaOH/ethanol (2 mL). After 1
h, the reaction mixture was neutralized with aqueous 2 N HCl.
The solvent was then removed under reduced pressure, and
the residue was purified by chromatography to give 17 (60 mg,
57% from 16): clear oil; Rf 0.20 (30% methanol/EtOAc); IR
(neat) 3368, 1729 cm-1 1H NMR (400 MHz, CD3OD) δ 1.86
;
(m, 1H), 2.14 (m, 1H), 3.14 (br t, J ) 7.0 Hz, 1H), 3.30 (m, 1H
partially hidden under residual CD2HOD), 3.38 (t, J ) 6.5 Hz,
1H), 3.64-3.86 (m, 9H), 4.08 (d, J ) 3.0 Hz, 1H), 4.19 (ABq,
∆δ ) 0.13 ppm, J ) 14.4 Hz, 2H), 4.36 (m, 1H), 4.45-4.58 (m,
6H), 4.63, 4.72 (both apparent d, J ) 12, 11 Hz resp, 1H ea),
7.30 (m, 20H); 13C NMR (75 MHz, CD3OD) δ 35.0, 64.9, 70.4,
72.4, 73.3, 74.3, 74.5, 74.9, 76.2, 76.6, 77.1, 78.1, 78.9, 80.7,
81.3, 81.4, 87.0, 87.3, 130.4, 130.9, 130.9, 130.9, 131.1, 141.2,
141.4, 141.5, 179.5; FABHRMS calcd for C48H50O12Na (M +
Na) 781.3200, found 781.3202.
3-O-Ca r b oxym et h yl-â-D-ga la ct op yr a n osyl 1-Ca r b a -r-
D-m a n n op yr a n osid e 3. A mixture of acid 17 (35 mg, 0.05
mmol), 20% Pd on carbon (35 mg), formic acid (0.1 mL), and
methanol (2 mL) was stirred under an atmosphere of hydrogen
(balloon) for 12 h. The reaction mixture was then purged with
argon and filtered through a bed of Celite. The filtrate was
concentrated in vacuo, and the residue was purified by
Sephadex LH-20 chromatography (H2O). Lyophilization of the
column extracts provided 3 (14 mg, 76%): white powder; [R]D
C
60H71O10Si (M + H) 979.4817, found 979.4818.
2-O-Acetyl-3,4-O-isop r op lylid en e-6-O-ter t-bu tyldiph en -
ylsilyl-â-D-ga la ctop yr a n osyl 1-Ca r ba -2,3.4,6-tetr a -O-ben -
zyl-r-D-m a n n op yr a n osid e 15. 1H NMR (300 MHz, CDCl3)
δ 1.17 (s, 9H), 1.28, 1.61 (both s, 3H ea), 1.70 (s, 3H), 2.08 (m,
1H), 3.58 (dt, J ) 4.8, 9.4 Hz, 1H), 3.73 (dd, J ) 2.6, 5.5 Hz,
1H), 3.76-3.92 (m, 4H), 3.98 (dd, J ) 5.1, 7.3 Hz, 1H), 4.08
(m, 3H), 4.17 (dd, J ) 7.7, 9.5 Hz, 1H), 4.2 (dd, J ) 2.2, 5.1
Hz, 1H), 4.34-4.54 (m, 8H), 4.59 (apparent d, J ) 12.1 Hz,
1H), 5.38 (dd, J ) 7.7, 9.2 Hz, 1H), 7.10-7.90 (m, 26H), 7.82
(m, 4H).
6-O-ter t-Bu tyldiph en ylsilyl-â-D-galactopyr an osyl 1-Car -
ba -2,3.4,6-tetr a -O-ben zyl-r-D-m a n n o-p yr a n osid e 16. A so-
lution of 1 M HCl in ether (3 mL) was added to a solution of
4 (500 mg, 0.51 mmol) in dry methanol (50 mL). The reaction
mixture was stirred at room temperature for 20 min, and then
neutralized by addition of a solution of sodium methoxide in
methanol. Removal of the volatiles under reduced pressure and
flash chromatography of the residue provided 16 (300 mg,
63%): clear oil; Rf 0.50 (50% EtOAc/petroleum ether); IR (neat)
3369 cm-1; 1HNMR (400 MHz, CDCl3) δ 1.05 (s, 9H), 1.39 (br
1
+57 (c 0.75, 1:1 methanol/H2O); H NMR (500 MHz, D2O) δ
1.90 (dt, J ) 7.5, 15 Hz, 1H), 2.11 (ddd, J ) 1.5, 7.5, 15 Hz,
1H), 3.31 (dt, J ) 3.0, 8.0 Hz, 1H), 3.4 (dt, J ) 3.0, 9.5 Hz,
1H), 3.53-3.74 (m, 7H), 3.79 (m, 2H), 3.91 (br s, 1H), 4.08 (d,
J ) 3.0 Hz, 1H), 4.11 (ABq, ∆δ ) 0.04 ppm, J ) 12 Hz, 2H),
4.19 (t, J ) 7.0 Hz, 1H); 13C NMR (75 MHz, D2O) δ 34.1, 64.7,
65.0, 69.4, 70.8, 71.6, 73.2, 73.9, 74.3, 77.5, 79.1, 80.8, 81.7,
86.6, 181.5; FABMS 421 (M + Na).
Ack n ow led gm en t . This investigation was sup-
ported by NIH grants RR 03037 (RCMI) and GM 57865.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
data for compounds 3, 4, 9, and 14-17. This material is
J O991898H