Core Tetrasaccharide of T. cruzi GIPLs
recrystallization in hexane to give 7 (3.60 g, 8.58 mmol, 91%):
Rf 0.52 (toluene/EtOAc 9:1); [R]D) -46 (c 1.2, CHCl3); mp 39-
40 °C (from hexane); IR νmax cm-1 3085, 3030, 2980, 2923, 2870,
2215, 2110, 1647, 1498, 1465, 1453, 1428, 1389, 1387, 1355,
1280, 1264, 1147, 1114, 1092, 1055, 1000, 924, 752, 698. 680,
617, 566, 550, 478; 1H NMR (300 MHz, CDCl3), δ 1.31 (t, 3H,
J ) 7.4 Hz), 2.65-2.83 (m, 2H), 3.33-3.51 (m, 4H), 3.63 (dd,
1H, J ) 4.4 11.0 Hz), 3.70 (dd, 1H, J ) 1.9 11.0 Hz), 3.97-
4.32 (m, 4H), 4.25 (d, 1H, J ) 9.9 Hz), 4.86 (s, 2H), 5.14-5.30
(m, 4H), 5.83-5.96 (m, 2H), 7.27-7.41(m, 5H); 13C NMR (75.4
MHz, CDCl3), δ 14.9, 24.5, 66.0, 68.7, 72.3, 73.6, 75.5, 77.5,
79.3, 84.1, 84.9, 116.8, 116.9, 127.8, 128.0 (2C), 128.3 (2C),
134.4, 134.5, 137.7; MALDI-TOF Calcd for C21H29N3O4S [M +
) 5.0 Hz), 5.12-5.30 (m, 6H), 5.33 (dd, 1H, J ) 4.4 8.2 Hz),
5.83-5.96 (m, 2H), 7.28-7.41 (m, 5H); 13C NMR (75.4 MHz,
CDCl3) δ 10.0, 20.1, 20.3, 26.9, 27.0 (3C), 27.1 (3C), 27.2 (3C),
29.6, 38.7, 38.8, 39.0, 43.0, 45.1, 47.8, 51.5, 63.0, 67.8, 69.6,
71.2, 71.3, 71.5, 71.7, 72.5, 73.7 74.7, 75.3, 75.5, 77.7, 79.4,
98.0, 116.7, 117.4, 118.0, 127.8, 128.1, 128.4, 134.4, 134.7,
138.0, 176.6, 177.2, 177.6; MALDI-TOF calcd for C50H73N3O13
[M + Na]+ 946.5, found [M + Na]+ 946.5. Anal. Calcd for
C50H73N3O13: C, 64.98; H, 7.96. Found: C, 65.09; H, 8.02.
6-O-(4,6-Di-O-allyl-2-azido-3-O-benzyl-2-deoxy-r-D-glu-
copyranosyl)-2,3-O-(D-1,7,7-trimethyl[2.2.1]bicyclohept-
6-ylidene)-D-myo-inositol (22). To a solution of compound 5
(2.50 g, 2.71 mmol) in MeOH (20 mL) was added NaOH (4.36
g, 108.9 mmol). The solution was refluxed for 30 min, diluted
with toluene, and washed sequently with saturated aqueous
NaHCO3 and water. The organic phase was dried, filtered, and
concentrated. FC (toluene/EtOAc 3:1 f 1:1) gave 22 (1.51 g,
2.25 mmol, 83%) as a colorless glue: Rf 0.50 (toluene/EtOAc
1:1); [R]D ) +41 (c 1.0, CHCl3); IR νmax cm-1 3455, 3081, 2934,
2876, 2110, 1453, 1384, 1321, 1262, 1206, 1146, 1113, 1083,
Na]+ 442.2, found [M
+
Na]+ 442.2. Anal. Calcd for
C21H29N3O4S: C, 60.12; H, 6.97. Found: C, 59.97; H, 6.75.
Ethyl 4,6-Di-O-allyl-2-azido-3-O-benzyl-2-deoxy-1-thio-
â-D-glucopyranoside S-Oxide (8). To a stirred solution of 7
(1.00 g, 2.38 mmol) in CH2Cl2 (20 mL) at -60 °C was added
m-CPBA (431 mg, 2.49 mmol). The mixture was allowed to
reach -20 °C during 30 min, diluted with CH2Cl2, washed with
saturated aqueous NaHCO3, dried, filtered, and concentrated.
FC (toluene/EtOAc 1:1) and reqrystallization from hexane gave
8 (674 mg, 1.55 mmol, 65%) as a white solid: Rf 0.36 (toluene/
EtOAc 1:1); [R]D ) -26 (c 1.0, CHCl3); mp 64-65 °C (from
hexane); IR νmax cm-1 3071, 3033, 2981, 2967, 2930, 2873, 2856,
2219, 2116, 1652, 1499, 1454, 1420, 1356, 1346, 1273, 1120,
1081, 1061, 1020, 994, 941, 916, 777, 752, 702, 677, 611, 552;
1H NMR (300 MHz, CDCl3) δ 1.38 (t, 3H, J ) 7.7 Hz), 2.84
(dq, 1H, J ) 15.4 7.7 Hz), 3.04 (dq, 1H, J ) 15.4 7.7 Hz), 3.41-
3.45 (m, 1H), 3.50 (t, 1H, J ) 9.1 Hz), 3.61 (t, 1H, J ) 9.1 Hz),
3.64 (dd, 1H, J ) 4.1 11.0 Hz), 3.70 (dd, 1H, 1.9 11.3 Hz), 3.82
(t, 1H, J ) 9.1 Hz), 3.99 (d, 1H, J ) 9.1 Hz), 4.02 (m, 2H),
4.13 (dddd, 1H, J ) 12.4 5.8 1.4 1.4 Hz), 4.28 (dddd, 1H, J )
12.4 5.8 1.4 1.4 Hz), 4.88 (s, 2H), 5.16-5.30 (m, 4H), 5.81-
5.96 (m, 2H), 7.31-7.42 (m, 5H); 13C NMR (75.4 MHz, CDCl3),
δ 7.2, 43.1, 60.9, 68.3, 72.4, 73.7, 75.7, 76.9, 80.0, 84.7, 90.6,
117.1, 117.2, 128.0, 128.1 (2C), 128.4 (2C), 134.2, 134.3, 137.5;
MALDI-TOF calcd for C21H29N3O5S [M + Na]+ 458.2, found
[M + Na]+ 458.2. Anal. Calcd for C21H29N3O5S: C, 57.91; H,
6.71. Found: C, 57.75; H, 6.87.
6-O-(4,6-Di-O-allyl-2-azido-3-O-benzyl-2-deoxy-r-D-glu-
copyranosyl)-1,4,5-tri-O-pivaloyl-2,3-O-(D-1,7,7-trimethyl-
[2.2.1]bicyclohept-6-ylidene)-D-myo-inositol (5). Method
A. Glycosylation Using Thioglucoside 7. To a solution of
thioglycoside 7 (1.00 g, 2.42 mmol), 1,4,5-tri-O-pivaloyl-2,3-O-
(D-1,7,7-trimethyl[2,2,1]bicyclohept-6-ylidene)-D-myo-inositol (6)24
(1.64 g, 2.90 mmol), and 4 Å molecular sieves (0.5 g) in dry
diethyl ether (45 mL) was added MeOTf (1.10 mL, 9.72 mmol).
The mixture was stirred for 16 h, Et3N (1 mL) was added, and
the mixture was diluted with DCM, filtered through Celite,
and concentrated. FC (light petroleum (45-65)/EtOAc 9:1)
gave 5 (1.14 g, 1.23 mmol, 51%) as a colorless syrup.
Method B. Glycosylation Using Sulfoxide 8. To a
solution of S-oxide 8 (500 mg, 1.15 mmol) in toluene (20 mL)
at -50 °C was added Tf2O (203 µL, 1.21 mmol). After 5 min,
a solution of alcohol 6 (1.04 g, 1.84 mmol) and 2,6-di-tert-butyl-
4-methylpyridine (283 mg, 1.38 mmol) in toluene (10 mL) was
added at -50 °C, and the reaction mixture was allowed to
reach 0 °C during 30 min, diluted with toluene, washed with
saturated aqueous NaHCO3, dried, filtered, and concentrated.
FC (light petroleum (45-65)/EtOAc 9:1) gave 5 (647 mg, 0.70
mmol, 61%) with traces of the â-anomer.
5: Rf 0.34 (light petroleum (45-65)/EtOAc 9:1); [R]D ) +49
(c 0.5, CHCl3); IR νmax cm-1 3078, 2967, 2936, 2874, 2108, 1740,
1480, 1459, 1397, 1369, 1279, 1205, 1140, 1114, 1038, 991, 970,
924, 748, 697; 1H NMR (300 MHz, CDCl3) δ 0.85 (s, 3H), 0.94
(s, 3H), 0.96 (s, 3H), 1.18-1.42 (m, 30H), 1.66-1.76 (m, 2H),
1.83-2.04 (m, 2H), 3.26 (dd, 1H, J ) 3.6 10.4 Hz), 3.55 (dd,
1H, J ) 1.9 11.0 Hz), 3.60-3.68 (m, 2H), 3.80-3.83 (m, 1H),
3.88 (dd, 1H, J ) 9.1 10.4 Hz), 3.92-3.99 (m, 1H), 4.02-4.17
(m, 3H), 4.22-4.31 (m, 2H), 4.55 (dd, 1H, J ) 4.4 7.4 Hz), 4.81
(d, 1H, J ) 10.4 Hz), 4.88 (d, 1H, J ) 10.4 Hz), 5.00 (t, 1H, J
1
1046, 1029, 967, 929, 700, 619; H NMR (300 MHz, CDCl3) δ
0.86 (s, 3H), 0.87 (s, 3H), 1.03 (s, 3H), 1.20-1.28 (m, 1H), 1.36-
1.45 (m, 1H), 1.52 (d, 1H, J ) 13.2 Hz), 1.68-1.76 (m, 2H),
2.00-2.06 (m, 2H), 3.29-3.41 (m, 3H), 3.52 (dd, 1H, J ) 3.9
10.2 Hz), 3.55 (dd, 1H, J ) 6.6 10.2 Hz), 3.64-3.80 (m, 4H),
3.85-4.14 (m, 7H), 4.29 (dddd, 1H, J ) 1.2 1.2 5.7 12.6 Hz),
4.37 (dd, 1H, J ) 3.9 6.0 Hz), 4.86 (ABq, 2H, J ) 10.5 Hz),
5.07 (d, 1H, J ) 3.9 Hz), 5.17-5.32 (m, 4H), 5.83-5.96 (m,
2H), 7.37-7.41 (m, 5H); 13C NMR (75.4 MHz, CDCl3) δ 9.8,
20.2, 20.6, 26.9, 29.7, 44.5, 45.1, 48.0, 51.7, 64.0, 68.5, 70.1,
71.4, 72.5, 72.9, 73.8, 74.6, 74.7, 75.5, 75.6, 78.3, 80.6, 84.5,
98.6, 117.3, 117.7, 118.2, 127.9, 128.0, 128.1, 128.3,128.4,
134.0, 134.2, 137.6; MALDI-TOF calcd for C35H49N3O10 [M +
Na]+ 694.3, found [M
+
Na]+ 694.3. Anal. Calcd for
C35H49N3O10: C, 62.58; H, 7.35. Found: C, 62.44; H, 7.28.
6-O-(4,6-Di-O-allyl-2-azido-3-O-benzyl-2-deoxy-r-D-glu-
copyranosyl)-4,5-O-isopropylidene-2,3-O-(D-1,7,7-tri-
methyl[2.2.1]bicyclohept-6-ylidene)-D-myo-inositol (23).
Compound 22 (900 mg, 1.34 mmol) was treated with 2,2-
dimethoxypropane (4.12 mL, 33.5 mmol) and pyridinium
p-toluene-4-sulfonate (50 mg, 0.20 mmol) in DMF (8 mL). After
8 h, solid NaHCO3 (0.4 g) was added, and the solution was
diluted with toluene and washed with water. The organic
phase was dried, filtered, and concentrated followed by FC
(toluene/EtOAc 15:1 f 9:1) to give 23 (620 mg, 0.87 mmol,
65%) as a colorless syrup: Rf 0.54 (toluene/EtOAc 9:1); [R]D
)
+95 (c, CHCl3); IR νmax cm-1 3074, 2986, 2935, 2872, 2107,
1497, 1477, 1454, 1383, 1372, 1320, 1235, 1117, 1080, 1054,
1
1027, 1005, 925, 874, 852, 838, 795, 747, 698; H NMR (300
MHz, CDCl3) δ 0.88 (s, 3H), 0.89 (s, 3H), 1.02 (s, 3H), 1.16-
1.24 (m, 1H), 1.36-1.41 (m, 1H), 1.42 (s, 3H), 1.43 (s, 3H), 1.47
(d, 1H, J ) 12.9 Hz), 1.67-1.76 (m, 1H), 1.79 (t, 1H, J ) 4.5
Hz), 1.99-2.09 (m, 2H), 2.72 (d, 1H, J ) 1.5 Hz), 3.35 (dd, 1H,
J ) 3.6 10.3 Hz), 3.53-3.66 (m, 3H), 3.72 (dd, 1H, J ) 3.0
11.0 Hz), 3.88-3.95 (m, 2H), 3.98 (ddd, 1H, J ) 1.4 1.4 5.8
12.9 Hz), 4.04-4.21 (m, 6H), 4.30 (ddd, 1H, J ) 1.4 1.4 5.8
12.1 Hz), 4.42 (dd, 1H, J ) 3.3 6.9 Hz), 4.84 (d, 1H, J ) 10.7
Hz), 4.89 (d, 1H, J ) 10.7 Hz), 5.14 (d, 1H, J ) 3.6 Hz), 5.15-
5.32 (m, 4H), 5.86-6.00 (m, 2H), 7.25-7.42 (m, 5H); 13C NMR
(75.4 MHz, CDCl3) δ 9.7, 20.1, 20.4, 26.8, 27.1, 27.2, 29.8, 42.9,
45.1, 48.0, 51.5, 63.1, 67.9, 70.7, 72.3, 72.6, 73.9, 74.8, 74.9,
75.3, 76.4, 77.7, 78.0, 78.2, 80.0, 96.8, 112.2, 117.1, 117.2, 118.5,
127.8, 128.0, 128.4, 134.5, 134.6, 138.0; MALDI-TOF calcd for
C38H53N3O10 [M + Na]+ 734.4, found [M + Na]+ 734.4. Anal.
Calcd for C38H53N3O10: C, 64.12; H, 7.50. Found: C, 64.28; H,
7.39.
6-O-(4,6-Di-O-allyl-2-azido-3-O-benzyl-2-deoxy-r-D-
glucopyranosyl)-1-di-O-benzylphosphoryl-4,5-O-isopropyli-
dene-2,3-O-(D-1,7,7-trimethyl[2.2.1]bicyclohept-6-
ylidene)-D-myo-inositol (24). To a solution of 23 (500 mg,
0.70 mmol) and dibenzyl diisopropyl phosphoramidite (411 mg,
1.19 mmol) in CH2Cl2 (10 mL) was added 1H-tetrazole (172
J. Org. Chem, Vol. 70, No. 18, 2005 7205