C. Gallo-Rodriguez et al. / Tetrahedron 58 (2002) 9373–9380
9379
3.1.10. Benzyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyrano-
syl-(1!3)-4,6-di-O-acetyl-2-O-pivaloyl-b-D-galactopyr-
anosyl-(1!6)-[2,3,5,6-tetra-O-benzoyl-b-D-galactofura-
nosyl-(1!4)]-2-acetamido-3-O-benzoyl-2-deoxy-a-D-
glucopyranoside (17). To a stirred solution of 2,3,4,6-tetra-
O-acetyl-b-D-galactopyranosyl-(1!3)-4,6-di-O-acetyl-2-
O-pivaloyl-a,b-D-galactopyranose (15, 313 mg, 0.46 mmol),
trichloroacetonitrile (0.23 mL, 2.31 mmol) in anhydrous
Cl2CH2 (5 mL) cooled to 08C, DBU (0.027 mL,
0.185 mmol) was slowly added. After 45 min, the solution
was concentrated under reduced pressure and the residue
was purified by column chromatography (3:1:0.3 toluene–
EtOAc–TEA) to give 334 mg of syrupy O-(2,3,4,6-tetra-O-
acetyl-b-D-galactopyranosyl-(1!3)-5,6-di-O-acetyl-2-O-
pivaloyl-a-D-galactopyranosyl) trichloroacetimidate (16,
88%): Rf 0.63 (1:1 toluene–EtOAc); 1H NMR (CDCl3,
200 MHz): d 8.69 (s, 1H, NH), 6.55 (d, 1H, J¼3.7 Hz, H-1),
5.57 (dd, 1H, J¼3.7, 1 Hz, H-4), 5.30–5.40 (m, 2H), 5.10
(dd, 1H, J¼10.6, 7.7 Hz, H-20), 4.91 (dd, 1H, J¼10.6,
3.7 Hz, H-30), 4.70 (d, 1H, J¼7.7 Hz, H-10), 4.45–4.10 (m,
5H), 4.00 (dd, 1H, J¼7.0, 11.3 Hz), 3.86 (t, 1H, J¼7 Hz),
2.18, 2.16, 2.07, 2.04, 1.99, 1.97 (6s, 18H, CH3CO), 1.21 (s,
9H, (CH3)3CCO; 13C NMR (CDCl3, 50.3 MHz): d 177.2,
170.4, 170.1, 169.9, 169.0 (CO), 160.5 (CN), 100.5 (C-10),
93.40 (C-1), 71.0, 70.8, 70.5, 69.8, 69.4, 68.8, 66.8, 62.0p
(C-6 ), 61.2p (C-6), 38.8 ((CH3)3C), 27.2 ((CH3)3C), 20.7,
20.5 (CH3CO).
1H, J¼3.6, 9.6, 10.7 Hz, H-2), 4.26–4.32 (m, 3H), 4.21 (dd,
1H, J¼6.0, 11.2 Hz, 1H), 4.18–4.11 (m, 4H), 4.00 (dd, 1H,
J¼6.6, 11.4 Hz), 3.9 (t, 1H, J¼9.6 Hz, H-4), 3.86–3.77 (m,
4H), 2.16, 2.09, 2.04, 2.00 (4s, 12H, CH3CO), 1.95 (s, 6H,
CH3CO), 1.76 (s, 3H, CH3CONH), 1.21 (s, 3H, C(CH3)3);
13C NMR (Cl3CD, 125 MHz): d 175.9, 170.4, 170.1, 170.0,
169.9, 169.3, 166.7, 165.8, 165.06, 165.5, 165.4 (CO0)0,
136.9–128.0 (arom.), 106.8 (C-1 ), 101.3, 100.9 (C-1 ,
C-1000), 95.9 (C-1), 82.3, 81.9 (C-40, C-20), 76.8, 75.7, 74.8,
72.3, 71.2, 70.9, 70.6, 70.4, 70.2, 70.0, 69.3 (PhCH2), 69.0,
68.2, 68.0 (C-6), 66.6, 63.3 (C-60), 61.6, 60.8 (C-600, 6000),
52.0 (C-2), 38.6 ((CH3)3C), 27.2 ((CH3)3C), 23.0
(CH3CONH), 20.6, 20.5 (CH3CO). Anal. calcd for
C85H91NO33·1/2H2O: C, 61.35; H, 5.57. Found: C 61.20,
H 5.23.
3.1.11. Benzyl b-D-galactopyranosyl-(1!3)-b-D-galacto-
pyranosyl-(1!6)-[b-D-galactofuranosyl-(1!4)]-2-aceta-
mido-2-deoxy-a-D-glucopyranoside (18). To a suspension
of 17 (400 mg, 0.24 mmol) in anhydrous MeOH (6 mL)
cooled at 08C, 1 M NaOMe in MeOH (6 mL, 6 mmol) was
added. After stirring for 3.5 h at room temperature and 16 h
at 58C, the solution was passed through a column
(1.5£6 cm) containing Amberlite IR 120 plus resin. After
concentration under vacuum, the residue was dissolved in
H2O, and the solution was washed with ether (10 mL) and
1:1 EtAcO–n-hexane (2£10 mL), and concentrated to
afford 18 (0.162 g, 0.203 mmol, 85%) which slowly
crystallized by addition of methanol. Mp 158–1608C
(methanol). Rf 0.47 (7:1:2 n-propanol–ethanol–water),
[a]D¼38.28 (c 1, H2O); 1H NMR (D2O, 500 MHz): d
7.39–7.34 (m, 5H), 5.10 (d, 1H, J¼2 Hz, H-10), 4.88 (d, 1H,
J¼3.5 Hz, H-1), 4.70, 4.51 (2d, 2H, J¼12.0 Hz, PhCHH),
4.57 (d, 1H, J¼7.6 Hz, H-100), 4.42 (d, 1H, J¼7.8 Hz, H-1000),
4.13 (d, 1H, J¼3.4 Hz), 4.09 (dd, 1H, J¼11.5, 2.0 Hz),
4.02–4.05 (m, 3H), 3.91 (ddd, 1H, J¼2.0, 9.9, 3.6 Hz),
3.87–3.53 (m, 18H), 1.90 (s, 3H, CH3CONH); 13C NMR
(D2O, 500 MHz): d 174.8 (CO), 137.5, 129.3, 129.1, 129.0
(arom.), 108.2 (C-10), 0104.9, 103.5 (C-100, C-1000), 96.4 (C-1),
83.2, 82.5 (C-40, C-2 ), 81.6, 77.8, 76.6, 75.6, 75.3, 73.1,
71.6, 71.1, 70.5 (PhCH2), 70.4, 70.3, 70.0, 69.2, 69.1,
68.0 (C-6), 63.3 (C-60), 61.5 (C-600,6000), 54.1 (C-2), 22.3
(CH3CONH). Anal. calcd for C33H51NO21: C 49.68; H 6.44.
Found: C 49.74, H 6.46.
Compound 16 may be stored in a freezer (2208C) for
several weeks without appreciable decomposition.
A suspension of 16 (334 mg, 0.406 mmol), benzyl (2,3,5,6-
tetra-O-benzoyl-b-D-galactofuranosyl)-(1!4)-2-acetamido-
3-O-benzoyl-2-deoxy-a-D-glucopyranoside (8, 400 mg,
˚
0.406 mmol), activated 4 A powdered molecular sieves in
anhydrous Cl2CH2 (10 mL) was vigorously stirred under an
argon atmosphere at rt for 30 min. The reaction mixture was
cooled to 2128C and TMSOTf (29 mL; 0.162 mmol) was
slowly added and the stirring continued for 1 h. The reaction
was quenched by addition of TEA (23 mL, 0.162 mmol),
filtered and concentrated. In order to improve separation
from remaining compound 8 and by-product 15, the mixture
was acetylated. The crude product was dissolved in dry
pyridine (2 mL), cooled to 08C, and then acetic anhydride
(2 mL) was added, and stirring continued at room
temperature for 1 h. The mixture was quenched by addition
of MeOH (2 mL) and then diluted with Cl2CH2. The organic
solution was sequentially washed with 10% HCl
(2£40 mL), H2O (40 mL), saturated aqueous NaHCO3
(2£40 mL) and H2O until it reached pH 7, dried (MgSO4)
and concentrated. The residue was purified by column
chromatography (5:2 toluene–EtOAc) to give 0.45 g of an
amorphous and hygroscopic solid identified as 17 (67%): Rf
3.1.12. b-D-Galactopyranosyl-(1!3)-b-D-galactopyra-
nosyl-(1!6)-[b-D-galactofuranosyl-(1!4)]-2-aceta-
mido-2-deoxy-a-D-glucopyranose (1). A suspension of
benzyl b-D-galactopyranosyl-(1!3)-b-D-galactopyranosyl-
(1!6)-[b-D-galactofuranosyl-(1!4)]-2-acetamido-2-deoxy-
a-D-glucopyranoside (18, 80 mg, 0.10 mmol) in a mixture
of 9:1 methanol–water (3.5 mL) and 10% Pd/C Deguzza
type E101 NE/W (Aldrich) (200 mg), was hydrogenated for
8 h at 45 psi (3 atm). The catalyst was filtered over Celite,
and the filtrate was concentrated. After dissolving the
residue in water, the resulting solution was passed through a
C8 cartridge. Evaporation of the solvent afforded compound
1 (60 mg, 85%) as a glassy solid. Rf 0.27 and 0.22 (7:1:2
n-propanol–ethanol–water), [a]D¼229.88 (c 1, MeOH);
1H NMR (D2O, 500 MHz): d anomeric region 5.16 (d, 0.7H,
J¼3.15 Hz, H-1a GlcNAc), 5.12 (bs, 1 Hz, H-10 Galf), 4.58
(d, 1H, J¼7.5 Hz, H-100), 4.45 (d, 0.3H, J¼7.7 Hz, H-1b
GlcNAc), 4.44 (d, 1H, J¼7.8 Hz, H-1000); 13C NMR (D2O,
1
0.39 (1:1 toluene–EtOAc), [a]D¼þ21.18 (c 1, Cl3CH); H
NMR (CDCl3, 500 MHz): d 8.02, 7.94, 7.90, 7.86, 7.80 (5d,
10H, J¼7.3 Hz, arom), 7.60–7.22 (m, 20H, arom), 05.76 (0d,
1H, J¼9.6 Hz, NH), 5.67–5.56 (m, 3H, H-3, H-3 , H-5 ),
5.36 (d, 1H, J¼3.09 Hz, H-400), 5.35 (d0, 1H, J¼4.3 Hz, H-4000),
5.28 (bs, 1H, H-2 ), 5.25 (bs, 1H, H-1 ), 5.25 (dd, 0100H, J¼9.8,
8.2 Hz, H-200), 5.05 (dd, 1H, J¼10.6, 7.8 Hz, H-2 ), 4.92 0(00d,
1H, J¼3.6 Hz, H-1), 4.86 (dd, 1H, J¼10.6, 3.6 Hz, H-3 ),
4.81, 4.49 (2d, 2H, J¼11.9 Hz, PhCHH), 4.53 (d, 1H,
J¼7.7 Hz, H-1000), 4.50 (d, 1H, J¼8.2 Hz, H-100), 4.52 (ddd,