Hendel et al.
JOCArticle
Methyl 2-Acetamido-3-O-(2,3,4,6-tetra-O-acetyl-β-D-gluco-
pyranosyl)-4-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-6-O-
benzyl-2-deoxy-β-D-glucopyranoside (14). Alcohol 11 (16 mg,
0.029 mmol) was coupled to the donor 1 (71 mg, 0.145 mmol,
5.0 equiv) in CH2Cl2 (1.0 mL) according to the general protocol.
Column chromatography (9:1 EtOAc:hexanes) of the residue
gave the trisaccharide 14 (21 mg, 88%) as a colorless glass. [R]D
-62 (c 1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.42-7.29
(m, 5H, Ar), 6.39 (d, 1H, J = 8.0 Hz, NH), 5.26-5.15 (m, 2H,
H-30, H-300), 5.14-5.01 (m, 2H, H-40, H-400), 5.00-4.88 (m, 2H,
H-20, H-200), 4.79 (d, 1H, J = 8.0 Hz, H-100), 4.54 (s, 2H, CH2Ph),
4.43 (d, 1H, J = 8.0 Hz, H-10), 4.38-4.29 (m, 3H, H-1, H-6a0,
H-6a00), 4.13 (dd, 1H, J = 12.5, 2.2 Hz, H-6b00), 4.08-3.92 (m,
4H, H-2, H-3, H-4, H-6b0), 3.82-3.64 (m, 4H, H-5, H-6a, H-6b,
H-50), 3.54-3.48 (m, 1H, H-500), 3.35 (s, 3H, OCH3), 2.05, 2.04,
2.03, 2.02, 1.99, 1.99, 1.98, 1.97 (8s, 27H, 9 ꢀ COCH3); 13C
NMR (100 MHz, CDCl3) δ 171.0, 170.6, 170.4, 169.9 (CdO),
148.1, 138.6, 128.9, 128.4, 128.3 (Ar), 101.6 (C-1), 99.2 (C-10, C-
100), 75.0 (C-5), 73.8 (C-3), 73.2 (CH2Ph), 72.4 (C-4), 72.3, 71.7
(C-30, C-300), 71.6 (C-50, C-500), 70.1 (C-20, C-200), 68.6 (C-6), 68.5
(C-40, C-400), 61.7 (C-60, C-600), 56.5 (OCH3), 50.1 (C-2), 23.5,
21.3, 21.1, 21.0 (COCH3); HRESIMS calcd for C44H59NO24
[M þ Na]þ 1008.3325, found 1008.3318.
H-6a00), 4.13-3.95 (m, 4H, H-3, H-4, H-6b0, H-6b00), 3.82-3.69
(m, 3H, H-2, H-6a, H-6b), 3.53-3.39 (m, 5H, H-5, OCH3, H-
500), 2.16, 2.13, 2.07, 2.03, 2.01, 2.00, 1.99, 1.98, 1.97 (9s, 27H, 9 ꢀ
COCH3); 13C NMR (150 MHz, CDCl3) δ 170.9, 170.6, 170.1,
170.0, 169.7, 169.3 (CdO), 137.9, 128.6, 128.0 (Ar), 102.5 (C-1),
101.1 (C-10), 98.9 (C-100), 77.0 (C-3), 74.7 (C-4), 74.1 (C-5), 73.7
(CH2Ph), 72.7 (C-400), 72.1 (C-500), 71.3 (C-200), 69.5 (C-20), 68.7
(C-30, C-50, C-300), 68.1 (C-6), 66.6 (C-40), 62.8 (C-600), 62.1
(C-60), 56.7 (OCH3), 54.1 (C-2), 23.5, 21.0, 20.8, 20.7,
20.6 (COCH3); HRESIMS calcd for C44H59NO24 [M þ H]þ
986.3505, found 986.3533.
Methyl 2-Acetamido-3-O-(2,3,4-tri-O-acetyl-r-L-fucopyano-
syl)-4-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)- 6-O-ben-
zyl-2-deoxy-β-D-glucopyranoside (21). Alcohol 18 (13 mg,
0.021 mmol) was coupled to the donor 1 (60 mg, 0.123 mmol,
5.0 equiv) in CH2Cl2 (0.8 mL) according to the general protocol.
Column chromatography (10:1 EtOAc:hexanes) of the residue
gave an inseparable mixture of the acceptor 18 and trisaccharide
21 (10 mg). The yields of 18 and 21 in the mixture were
determined by NMR to be 34% and 26%, respectively. An
analytical sample of 21 was obtained after additional column
chromatography (8:2 CH2Cl2:acetone). [R]D -59 (c 0.4, CH2-
Cl2); 1H NMR (400 MHz, CDCl3) δ 7.43-7.31 (m, 5H, Ar), 5.56
(d, 1H, J = 8.5 Hz, NH), 5.34 (d, 1H, J = 3.8 Hz, H-10), 5.28 (dd,
1H, J = 10.8, 3.2 Hz, H-20), 5.19 (d, 1H, J = 2.8 Hz, H-40),
5.03-4.87 (m, 3H, H-30, H-400, H-300), 4.78 (t, 1H J = 8.6 Hz,
H-200), 4.75-4.63 (m, 2H, CHHPh, H-50), 4.61-4.38 (m, 4H,
H-1, H-6a00, CHHPh, H-100), 4.06-3.89 (m, 2H, H-3, H-4,
H-6b00), 3.84-3.69 (m, 2H, H-6a, H-6b), 3.64 (q, 1H, J =
7.0 Hz, H-2), 3.49-3.39 (m, 1H, H-5), 3.36 (s, 3H, OCH3),
3.31-3.21 (m, 1H, H-500), 2.06, 2.01, 2.00, 1.99, 1.94, 1.93, 1.90,
1.89 (8s, 24H, 8 ꢀ COCH3), 1.07 (d, 3H, J = 6.5 Hz, H-60); 13C
NMR (150 MHz, CDCl3) δ 171.1, 170.7, 170.5, 170.2, 169.5,
169.4, 169.1(CdO), 137.8, 128.7, 128.5, 128.4, 128.1, 128.0,
127.8 (Ar), 100.9 (C-1), 99.6 (C-100), 95.1 (C-10), 74.6 (C-3),
74.5 (C-5), 73.6 (CH2Ph), 73.3 (C-500), 72.7 (C-4), 72.2 (C-30),
71.7 (C-40), 71.1 (C-200), 68.6 (C-400), 68.0 (C-6), 67.7 (C-300), 67.6
(C-20), 64.5 (C-50), 61.0 (C-600), 56.6 (OCH3), 56.3 (C-2), 23.4,
21.0, 20.7, 20.6 (COCH3), 15.7 (C-60); HRESIMS calcd for
C42H57NO22 [M þ Na]þ 950.3270, found 950.3266.
Methyl 2-Acetamido-3-O-(2,3,4-tri-O-acetyl-β-L-fucopyrano-
syl)-4-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-6-O-benzyl-
2-deoxy-β-D-glucopyranoside (15). Alcohol 12 (13 mg, 0.021
mmol) was coupled to the donor 1 (52 mg, 0.106 mmol,
5.0 equiv) in CH2Cl2 (0.8 mL) according to the general protocol.
Column chromatography (9:1 EtOAc:hexanes) of the residue
gave an inseparable mixture of the acceptor 12 and trisaccharide
15 (16 mg). The yields of 12 and 15 in the mixture were
determined by NMR to be 24% and 63%, respectively. An
analytical sample of trisaccharide 15 was obtained upon addi-
tional column chromatography (25:1 CHCl3:MeOH). [R]D -5
(c 0.4, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.44-7.30 (m,
5H, Ar), 5.98 (d, 1H, J = 8.1 Hz, NH), 5.29 (d, 1H, J = 3.4 Hz,
H-40), 5.19-4.99 (m, 4H, H-20, H-30, H-300, H-400), 4.93 (d, 1H,
J = 8.2 Hz, H-200), 4.82 (d, 1H, J = 7.8 Hz, H-10), 4.71-4.50 (m,
4H, H-1, H-100, CH2Ph), 4.24 (dd, 1H, J = 12.4, 4.0 Hz, H-6a00),
4.14 (t, 1H, J = 6.8 Hz, H-3), 4.03-3.94 (m, 2H, H-4, H-6b00),
3.86 (q, 1H, J = 6.8 Hz, H-50), 3.83-3.70 (m, 3H, H-2, H-6a,
H-6b), 3.64-3.55 (m, 1H, H-5), 3.48 (s, 3H, OCH3), 3.44-3.38
(m, 1H, H-500), 2.18, 2.08, 2.04, 2.03, 1.98 (5s, 24H, 8 ꢀ COCH3),
1.24 (d, 3H, J = 6.4 Hz, H-60); 13C NMR (100 MHz, CDCl3) δ
171.0, 170.5, 170.4 (CdO), 129.0, 128.4, 128.3 (Ar), 102.1 (C-1),
100.6 (C-10), 99.0 (C-100), 76.8 (C-3), 75.3 (C-5), 75.0 (C-4), 73.9
(CH2Ph), 72.9 (C-300), 72.4 (C-500, 72.0 (C-200), 71.6 (C-30), 70.8
(C-40), 70.0 (C-20), 69.8 (C-50), 69.4 (C-6), 68.5 (C-400), 61.8
(C-600), 57.0 (OCH3), 54.2 (C-2), 23.8, 21.4, 21.2, 21.1,
21.0 (COCH3), 16.4 (C-60); HRESIMS calcd for C42H57NO22
[M þ H]þ 928.3424, found 928.3434.
Methyl 2-Acetamido-4-O-(2,3,4,6-tetra-O-acetyl-β-D-glucop-
yranosyl)-3-O-(2,3,4-tri-O-acetyl-r-L-rhamnopyranosyl)-6-O-
benzyl-2-deoxy-β-D-glucopyranoside (22). Alcohol 19 (14 mg,
0.029 mmol) was coupled to the donor 1 (56 mg, 0.114 mmol,
5.0 equiv) in CH2Cl2 (0.8 mL) according to the general protocol.
Column chromatography (9:1 EtOAc:hexanes) of the residue
gave an inseparable mixture of the acceptor 19 and trisaccharide
22 (12 mg). The yields of 19 and 22 in the mixture were
determined by NMR to be 43% and 27%, respectively. An
analytical sample of 22 was obtained after additional column
chromatography (8:2 CH2Cl2:acetone). [R]D -9 (c 0.8, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ 7.51-7.31 (m, 5H, Ar), 6.07 (d,
1H, J = 8.6 Hz, NH), 5.27-5.19 (m, 2H, H-20, H-30), 5.16-5.01
(m, 2H, H-40, H-300), 4.98 (s, 1H, H-10), 4.95-4.77 (m, 4H, H-1,
CHHPh, H-200, H-400), 4.61 (d, 1H, J = 8.2 Hz, H-100), 4.53 (d,
1H, J = 11.9 Hz, CHHPh), 4.46-4.36 (m, 1H, H-50), 4.32-4.10
(m, 3H, H-3, H-6a00, H-6b00), 3.96 (t, 1H, J = 7.6 Hz, H-4), 3.82
(d, 2H, J = 3.3 Hz, H-6a, H-6b), 3.61-3.54 (m, 1H, H-5),
3.53-3.40 (m, 5H, H-2, H-500, OCH3), 2.10, 2.08, 2.05, 2.00,
1.97, 1.96, 1.95, 1.94 (8s, 24H, 8 ꢀ COCH3), 1.24 (d, 3H, J =
6.3 Hz, H-60); 13C NMR (100 MHz, CDCl3) δ 172.8, 171.1,
170.7, 170.4, 170.2, 169.9, 169.5, 169.3 (CdO), 128.6, 128.1,
128.0 (Ar), 100.2 (C-1), 98.9 (C-100), 96.3 (C-10), 74.2 (C-5), 73.8
(C-4), 73.6 (CH2Ph), 73.1 (C-3), 72.7 (C-300), 71.8 (C-500), 71.4
(C-400), 71.0 (C-40), 70.1 (C-30), 69.3 (C-200), 69.0 (C-20), 68.2
(C-6), 66.3 (C-50), 62.7 (C-600), 56.8 (C-2), 56.8 (OCH3), 23.4,
21.0, 20.8, 20.7, 20.6 (COCH3), 17.1 (C-60); HRESIMS calcd for
C42H57NO22 [M þ H]þ 928.3450, found 928.3492.
Methyl 2-Acetamido-4-O-(2,3,4,6-tetra-O-acetyl-β-D-glucop-
yranosyl)-3-O-(2,3,4,6-tetra-O-acetyl-r-D-mannopyranosyl)-6-
O-benzyl-2-deoxy-β-D-glucopyranoside (20). Alcohol 17 (22 mg,
0.034 mmol) was coupled to the donor 1 (83 mg, 0.167 mmol,
5.0 equiv) in CH2Cl2 (1.2 mL) according to the general protocol.
Column chromatography (10:1 EtOAc:hexanes) of the residue
gave a colorless glass (21 mg) containing the trisaccharide 20
contaminated with some degraded donor. The yield of trisac-
charide 20 (18 mg, 55%) was calculated from the 1H NMR
spectrum while an analytical sample of trisaccharide 20 was
obtained after additional column chromatography (35:1 CHCl3:
MeOH). [R]D þ5 (c 0.6, CH2Cl2); 1H NMR (600 MHz, CDCl3)
δ 7.48-7.30 (m, 5H, Ar), 5.98 (d, 1H, J = 8.7 Hz, NH), 5.43
(s, 1H, H-20), 5.33-5.21 (m, 2H, H-30, H-40), 5.12 (d, 1H, J =
1.4 Hz, H-10), 5.09-4.96 (m, 2H, H-300, H-400), 4.89 (t, 1H, J =
8.1 Hz, H-200), 4.75 (d, 1H, J = 11.9 Hz, CHHPh), 4.60-4.47
(m, 3H, H-1, CHHPh, H-100), 4.34-4.13 (m, 3H, H-50, H-6a0,
8330 J. Org. Chem. Vol. 74, No. 21, 2009