J. Liao et al. / Carbohydrate Research 344 (2009) 1034–1038
1037
1.2. General procedure for the one-pot nucleoside synthesis
1H), 4.84 (d, J = 2.4 Hz, 1H), 4.30 (dd, J = 9.9, 14.4 Hz, 1H), 2.19,
2.18, 1.94, 1.91 (s, 4 ꢁ 3H), 1.56 (d, J = 4.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) d 169.5, 169.4, 169.1, 163.7, 150.8, 134.9, 111.7,
74.1, 73.2, 71.3, 68.6, 65.9, 20.9, 20.7, 20.4, 15.7, 12.4. HRMS (ESI)
Calcd for C17H22N2O9Na [M+Na+]: 421.1217. Found: 421.1218.
To a stirred suspension of base, glycosyl N-phenyltrifluoroace-
timidate, and 4 Å MS in dry CH3NO2 was added BSTFA (1.5 equiv
to base). The mixture was stirred at rt for 30 min and then TMSOTf
was added. Stirring was continued at rt until the glycosyl donor
was consumed as monitored by TLC. After Et3N was added to
quench the reaction, the 4 Å MS were removed by filtration. Evap-
oration of the solvent gave a residue that was further purified by
chromatography.
1.2.7. 1-(2,3,4-Tri-O-acetyl-
dihydropyridin-2-one (3dc)
+99.8 (c 1.0, CHCl3), 1H NMR (300 MHz, CDCl3) d 7.45 (d,
a-L-rhamnopyranosyl)-1,4-
½ ꢀ
a 2D5
J = 6.6 Hz, 1H), 7.32 (dt, J = 2.1, 6.6 Hz, 1H), 6.72 (d, J = 9.9 Hz,
1H), 6.53 (d, J = 9.0 Hz, 1H), 6.24 (t, J = 6.9 Hz, 1H), 5.47 (t,
J = 3.0 Hz, 1H), 5.37 (dd, J = 3.6, 9.6 Hz, 1H), 4.87 (d, J = 2.4 Hz,
1H), 4.33 (q, J = 7.5 Hz, 1H), 2.21, 2.18, 1.91 (s each, 3 ꢁ 3H), 1.61
(d, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 169.3, 169.2,
169.0, 161.8, 139.5, 132.6, 120.5, 106.1, 73.8, 72.3, 71.3, 68.5,
66.9, 20.7, 20.6, 20.1, 15.6. HRMS (ESI) Calcd for C17H21NO8Na
[M+Na+]: 390.1159. Found: 390.1167.
1.2.1. 1-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-1,2-
dihydropyridin-2-one (3bc)
½
a 2D5 +107.8 (c 1.1, CHCl3), 1H NMR (300 MHz, CDCl3) d 7.46 (d,
ꢀ
J = 6.0 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H), 6.51 (d, J = 9.3 Hz, 1H), 6.32–
6.23 (m, 2H), 5.53 (d, J = 2.7 Hz, 1H), 5.39 (dd, J = 9.0, 10.2 Hz, 1H),
5.23 (dd, J = 3.3, 10.2 Hz, 1H), 4.19–4.10 (m, 3H), 2.20, 2.04, 1.99,
1.94 (s each, 4 ꢁ 3H); 13C NMR (75 MHz, CDCl3) d 170.1, 169.7,
169.5, 169.4, 140.0, 132.8, 120.1, 106.4, 79.4, 73.5, 70.7, 68.1,
66.9, 61.1, 20.4, 20.3, 20.1. HRMS (ESI) Calcd for C19H23NO10Na
[M+Na+]: 448.1214. Found: 448.1221.
1.3. General procedure for O-glycosylation of 2-hydroxy-
pyridine
To a stirred suspension of 2c (1.5 equiv to the glycosyl donor) in
dry acetonitrile was added BSTFA (1 equiv to the base). The mix-
ture was stirred at rt for 30 min, during which time a clear solution
was formed. After the solvent was removed under reduced pres-
sure, the silylated base was obtained as a clear oil. Under argon
atmosphere, the activated base was dissolved in dry CH2Cl2, fol-
lowed by the addition of activated 4 Å MS and the glycosyl N-phe-
nyltrifluoroacetimidate (1.0 equiv). After subsequent addition of
TMSOTf, the resulting mixture was stirred at rt until the donor
was consumed completely; normally, 4–24 h was required. After
quenching the reaction with Et3N and removing 4 Å MS by filtra-
tion, the solvent was removed under reduced pressure. The result-
ing residue was further purified by column chromatography to give
the pure product.
1.2.2. 1-(2,3,4,6-Tetra-O-acetyl-D-mannopyranosyl) uracil (3ca)
1H NMR (300 MHz, CDCl3) d 8.74 (br s, 1H), 7.34 (d, J = 8.1 Hz,
1H), 6.16 (d, J = 9.9 Hz, 1H), 5.80 (d, J = 8.1 Hz, 1H), 5.49 (t,
J = 3.3 Hz, 1H), 5.37 (dd, J = 3.3, 9.9 Hz, 1H), 4.98 (d, J = 3.3 Hz,
1H), 4.67 (dd, J = 9.6, 13.2 Hz, 1H), 4.37–4.31 (m, 2H), 2.21 (s,
3H), 2.18 (s, 3H), 2.09 (s, 3H), 1.99 (s, 3H); 13C NMR (75 MHz,
CDCl3) d 170.3, 169.3, 169.1, 168.8, 163.0, 150.3, 139.6, 103.2,
75.7, 75.0, 67.9, 67.7, 65.6, 60.0, 20.6, 20.53, 20.47, 20.2. HRMS
(ESI) Calcd for C18H22NO11Na: 465.1116. Found: 465.1116.
1.2.3. 1-(2,3,4,6-Tetra-O-acetyl-a-D-mannopyranosyl) thymine
(3cb)
½
a 2D5 +27.6 (c 1.0, CHCl3), 1H NMR (300 MHz, CDCl3) d 8.70 (br s,
ꢀ
1H), 7.15 (s, 1H), 6.17 (d, J = 9.6 Hz, 1H), 5.50 (t, J = 3.3 Hz, 1H),
5.37 (dd, J = 3.3, 9.9 Hz, 1H), 4.98 (d, J = 2.7 Hz, 1H), 4.65 (m, 1H),
4.39–4.26 (m, 2H), 2.21, 2.20, 2.09, 1.97, 1.95 (s, 5 ꢁ 3H); 13C NMR
(75 MHz, CDCl3) d 170.4, 169.5, 169.2, 168.9, 163.5, 135.0, 111.9,
75.9, 74.8, 68.2, 68.0, 65.7, 60.2, 20.9, 20.7, 20.6, 20.4, 12.5. HRMS
(ESI) Calcd for C19H24N2O11Na [M+Na+]: 479.1270. Found: 479.1270.
1.3.1. 2-[(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-oxy]
pyridine (4b)
½
a 2D5 +24.7 (c 1.0, CHCl3), 1H NMR (300 MHz, CDCl3) d 8.18 (d,
ꢀ
J = 4.2 Hz, 1H), 7.66 (dd, J = 7.5, 7.8 Hz, 1H), 7.02 (t, J = 6.0 Hz,
1H), 6.84 (d, J = 7.8 Hz, 1H), 6.21 (d, J = 8.4 Hz, 1H), 5.55–5.47 (m,
2H), 5.19 (dd, J = 2.4, 10.2 Hz, 1H), 4.16 (s, 3H), 2.19 (s, 3H), 2.02
(s, 6H), 1.99 (s, 3H); 13C NMR (75 MHz, CDCl3) d 170.33, 170.28,
170.1, 169.5, 161.3, 146.7, 139.4, 118.9, 111.7, 93.8, 71.1, 71.0,
68.4, 67.0, 61.0, 20.70, 20.69, 20.66, 20.61. HRMS (ESI) Calcd for
C19H23NO10Na [M+Na+]: 448.1214. Found: 448.1221.
1.2.4. 1-(2,3,4,6-Tetra-O-acetyl-a-D-mannopyranosyl)-1,2-
dihydropyridin-2-one (3cc)
½
a 2D5
ꢀ
ꢂ42.6 (c 1.0, CHCl3), 1H NMR (300 MHz, CDCl3) d 7.42 (dd,
J = 1.8, 6.9 Hz, 1H), 7.32 (dt, J = 1.8, 9.3 Hz, 1H), 6.62 (d, J = 9.6 Hz,
1H), 6.52 (d, J = 8.7 Hz, 1H), 6.24 (dt, J = 1.5, 7.8 Hz, 1H), 5.50 (dd,
J = 3.6, 3.0 Hz, 1H), 5.43 (dd, J = 3.6, 9.3 Hz, 1H), 5.02 (dd, J = 1.8,
3.6 Hz, 1H), 4.62–4.34 (m, 3H), 2.22, 2.19, 2.08, 1.91 (s, 4 ꢁ 3H);
13C NMR (75 MHz, CDCl3) d 170.3, 169.3, 169.1, 169.0, 161.9,
139.7, 132.7, 120.7, 106.3, 75.6, 74.0, 68.2, 68.0, 66.7, 60.3, 20.7,
20.6, 20.5, 20.2. HRMS (ESI) Calcd for C19H23NO10Na [M+Na+]:
448.1214. Found: 448.1224.
1.3.2. 2-[(2,3,4,6-Tetra-O-acetyl-a-D-mannopyranosyl)-oxy]
pyridine (4c)
½
a 2D5 +23.6 (c 1.0, CHCl3), 1H NMR (300 MHz, CDCl3) d 8.20 (dd,
ꢀ
J = 1.5, 4.8 Hz, 1H), 7.69 (dt, J = 1.8, 8.4 Hz, 1H), 7.01 (t, J = 6.0 Hz,
1H), 6.86 (d, J = 8.1 Hz, 1H), 6.47 (d, J = 1.2 Hz, 1H), 5.58 (dd,
J = 3.3, 9.9 Hz, 1H), 5.45–5.36 (m, 2H), 4.26 (dd, J = 4.8, 12.0 Hz,
1H), 4.16–4.05 (m, 2H), 2.19, 2.06, 2.02, 2.00 (s, 4 ꢁ 3H); 13C NMR
(75 MHz, CDCl3) d 170.6, 170.0, 169.95, 169.7, 160.4, 147.1, 139.4,
118.7, 111.3, 91.8, 69.6, 69.0, 65.9, 62.2, 20.8, 20.7, 20.6. HRMS
(ESI) Calcd for C19H23NO10Na [M+Na+]: 448.1214. Found: 448.1224.
1.2.5. 1-(2,3,4-Tri-O-acetyl-a-L-rhamnopyranosyl) uracil (3da)
1H NMR (300 MHz, CDCl3) d 8.73 (br s, 1H), 7.40 (d, J = 9.1 Hz,
1H), 6.23 (d, J = 9.6 Hz, 1H), 5.80 (d, J = 9.1 Hz, 1H), 5.45 (s, 1H),
5.30 (dd, J = 3.3, 9.6 Hz, 1H), 4.84 (d, J = 1.8 Hz, 1H), 4.30 (dd,
J = 9.6, 14.4 Hz, 1H), 2.20, 2.17, 1.99 (s, 3 ꢁ 3H), 1.57 (d, J = 6.9 Hz,
3H); 13C NMR (75 MHz, CDCl3) d 169.5, 169.3, 169.1, 163.2, 150.6,
139.6, 103.2, 74.1, 73.5, 71.2, 68.5, 65.9, 20.8, 20.7, 20.3, 15.6. HRMS
(ESI) Calcd for C16H20N2O9Na [M+Na+]: 407.1067. Found: 407.1061.
1.3.3. 2-[(2,3,4-Tri-O-acetyl-a-L-rhamnopyranosyl)-oxy]
pyridine (4d)
½
a 2D5
ꢀ
ꢂ82.1 (c 1.0, CHCl3), 1H NMR (300 MHz, CDCl3) d 8.20 (d,
J = 3.9 Hz, 1H), 7.68 (dd, J = 6.9, 7.8 Hz, 1H), 6.99 (t, J = 6.0 Hz,
1H), 6.85 (d, J = 8.4 Hz, 1H), 6.39 (s, 1H), 5.53 (dd, J = 2.7, 10.5 Hz,
1H), 5.42 (s, 1H), 5.20 (dd, J = 9.9, 10.2 Hz, 1H), 4.06 (q, J = 5.7 Hz,
1H), 2.18, 2.06, 2.02 (s, 3 ꢁ 3H), 1.21 (d, J = 5.7 Hz, 3H); 13C NMR
(75 MHz, CDCl3) d 170.1, 170.0, 169.9, 160.6, 147.0, 139.3, 118.5,
1.2.6. 1-(2,3,4-Tri-O-acetyl-a-L-rhamnopyranosyl) thymine (3db)
1H NMR (300 MHz, CDCl3) d 8.87 (s, 1H), 7.17 (s, 1H), 6.24 (d,
J = 9.9 Hz, 1H), 5.46 (dd, J = 2.4, 3.0 Hz, 1H), 5.30 (dd, J = 3.6, 9.9 Hz,