The Journal of Organic Chemistry IR (Si) νmax 3050, 2933, 2859, 1 754, 1429, 1371, 1221, 1113, 1029 cm 1; 1H NMR (400.1 MHz, CDCl3) δ 7.67 7.63 (m, 4H), 7.41 7.35 (m, 6H), 6.17 (d, J = 1.5 Hz, 1H), 5.55 (dd, J = 6.3, 4.8 Hz, 1H), 5.43 (dd, J = 4.8, 1.5 Hz, 1H), 4.24 (dt, J = 6.3, 3.5 Hz, 1H), 3.76 (AB system, JAX = JBX = 3.5 Hz, JAB = 11.3 Hz, 2H), 2.10 (s, 3H), 2.03 (s, 3H), 1.93 (s, 3H), 1.05 (s, 9H); 13C NMR (100.6 MHz, CDCl3) δ 169.7, 169.48, 169.46, 135.60 (2C), 135.5 (2C), 133.0, 132.80, 129.84, 129.8, 127.8 (2C), 127.7 (2C), 98.2, 82.3, 74.5, 70.6, 63.2, 26.7 (3C), 20.9, 20.5, 20.5, 19.2. Anal. Calcd for C27H34O8Si: C, 63.01; H, 6.66. Found: C, 63.29; H, 6.78. Data for α-17: [α]2D0 +46.3 (c 1.2, acetone); IR (Si) νmax 3072, 2933, 2859, 1749, 1472, 1428, 1370, 1222, 1113, 1074, 1051, 1011 cm 1; 1H NMR (400.1 MHz, CDCl3) δ 7.68 7.63 (m, 4H), 7.45 7.35 (m, 6H), 6.46 (d, J = 4.5 Hz, 1H), 5.50 (dd, J = 6.3, 2.0 Hz, 1H), 5.41 (dd, J = 6.3, 4.5 Hz, 1H), 4.29 (∼q, J ≈ 2.5 Hz, 1H), 3.79 (AB system, J = 11.5, 3.0, 2.3 Hz, 2H), 2.11 (s, 3H), 2.10 (s, 3H), 2.07 (s, 3H), 1.05 (s, 9H); 13C NMR 100.6 MHz, CDCl3) δ 170.2, 169.9, 169.3, 135.6 (2C), 135.6 (2C), 132.8, 132.6, 130.3, 130.2, 127.8 (2C), 127.8 (2C), 94.5, 85.0, 70.6, 70.5, 63.4, 26.7 (3C), 21.1, 20.7, 20.3, 19.2. 1-β-[20,30-Di-O-acetyl-50-O-(tert-butyldiphenylsilyl)-D- ribofuranosyl]-2-nitroimidazole (β-18). A solution of β-17 (0.395 g, 0.77 mmol) in dry CH3CN (3 mL) was added to 2-nitroimi- dazole (0.087 g, 0.77 mmol) triethylsilylated according to general procedure A in dry CH3CN (2 mL) under argon. After the stirred mixture was cooled to 20 C, TESOTf (0.77 mL, 1 M in dry 1,2- C2H4Cl2) was added, and stirring was continued for 2 h while the temperature of the reaction mixture was allowed to slowly rise to 8 C in the cooling bath (TLC, hexanes/EtOAc, 2:1). Saturated aq NaHCO3 (10 mL) was added, and the mixture was extracted with EtOAc (3 10 mL). The combined organic layers were washed with water (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (hexanes/EtOAc, 3:1, Rf 0.47 for 2:1) to give nucleoside β-1818 (0.315 g, 72%) as yellow crystals; a trace of possibly α-anomer was detected by TLC: [α]2D0 +13.31 (c 1.3, acetone); mp 130 131 C (CHCl3/i-Pr2O) (lit.18 mp 52 53 C). Similarly, triacetate α-17 (0.395 g, 0.77 mmol) was reacted in the same way, except that the temperature was allowed to warm to rt within 2 h, and yielded (0.381 g, 87%) β-18; a trace of possibly α-18 could be detected in the crude product by TLC: IR (Si) νmax 2932, 1755, 1589, 1542, 1477, 1428, 1369, 1238, 1114, 1081, 1011 cm 1; the 1H and 13C NMR data agree with those of the literature.18 Anal. Calcd for C28H33N3O8Si: C, 59.24; H, 5.86; N, 7.40. Found: C, 58.98; H, 5.56; N, 7.14. 1-β- and 1-α-(20,30,5-Tri-O-benzoyl-D-ribofuranosyl)-2-ni- troimidazole (β- and α-20). A solution of 1-O-acetyl-2,3,5-tri-O- benzoyl-β-D-ribofuranose (0.605 g, 1.2 mmol, 1.2 equiv) in dry CH3CN (4.6 mL) was added to the stirred mixture of 2-nitroimidazole (0.113 g, 1.0 mmol; triethylsilylated according to general procedure A) in dry CH3CN (5.0 mL) under argon. TMSOTf (0.5 M, 2.4 mL, in dry CH2Cl2) was added, and stirring was continued at rt (23 C) for 1 h (TLC, hexanes/EtOAc, 2:1). A saturated aq solution of NaHCO3 (10 mL) was added, and the mixture was extracted with EtOAc (3 10 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (hexanes/EtOAc, 2:1; β-20, Rf 0.38; α-20, Rf 0.26) to yield β-20 (0.173 g, 31%) as a yellow oil and α-20 (0.235 g, 42%) as yellow crystals: mp 136 138 C (CHCl3/i-Pr2O) [lit.19 mp 138.5 140 C (CH2Cl2/MeOH)]. Data for β-20: [α]2D0 +27.47 (c 0.91, acetone); IR (Si) νmax 1733, 1541, 1479, 1452, 1366, 1268, 1118, 1094, 1071 cm 1; 1H NMR (400.1 MHz, CDCl3) δ 8.09 8.05 (m, 2H), 7.99 7.95 (m, 2H), δ 7.91 7.87 (m, 2H), 7.64 7.51 (m, 3H), 7.57 (d, J = 1.3 Hz, 1H), 7.50 7.44 (m, 2H), 7.43 7.38 (m, 2H), 7.37 7.32 (m, 2H), 7.12 (d, J = 1.3 Hz, 1H), 6.97 (d, J = 4.0 Hz, 1H), 5.86 (t, J = 5.6 Hz, 1H), 5.82 (dd, J = 5.6, 4.0 Hz, 1H), 4.86 (dd, J = 12.4, 2.7 Hz, 1H), 4.83 (∼td, J = 5.6, 3.5, 2.7 Hz, 1H), 4.70 (dd, J = 12.4, 3.5 Hz, 1H); 13C NMR ARTICLE (100.6 MHz, CDCl3) δ 166.0, 165.2, 164.8, 144.4 (br), 133.9, 133.9, 133.7, 129.9 (2C), 129.8 (2C), 129.7 (2C), 129.1, 129.1, 128.8 (2C), 128.6 (2C), 128.6 (2C), 128.3, 128.3, 121.5, 89.6, 80.7, 76.1, 70.2, 63.0. Data for α-20: [α]2D0 56.8 (c 1.07, acetone); IR (Si) νmax 1732, 1539, 1479, 1452, 1365, 1267, 1095, 1070, 1026 cm 1 1 ; H NMR (400.1 MHz, CDCl3) δ 8.14 8.09 (m, 2H), 7.71 7.67 (m, 2H), 7.64 7.56 (m, 3H), 7.54 7.46 (m, 5H), 7.34 7.27 (m, 4H), 7.23 (d, J = 1.3 Hz, 1H), 7.16 (d, J = 5.6 Hz, 1H), 6.30 (t, J = 5.6 Hz, 1H), 5.92 (dd, J = 5.6, 3.2 Hz, 1H), 5.06 (ddd ≈ q, J = 3.4 Hz, 1H), 4.79 (dd, J = 12.4, 3.4 Hz, 1H), 4.63 (dd, J = 12.4, 3.4 Hz, 1H); 13C NMR (100.6 MHz, CDCl3) δ 165.9, 165.0, 164.0, 144.6, 133.9, 133.8, 133.6, 129.7 (2C), 129.6 (2C), 129.4 (2C), 129.0, 128.7 (2C), 128.6 (2C), 128.5 (2C), 128.2, 128.2, 127.7, 122.5, 88.1, 82.7, 71.8, 71.3, 63.9. 1-β-(20,30,40,60-Tetra-O-acetyl-D-galactopyranosyl)-2-ni- troimidazole (β-22). A solution of 1,2,3,4,6-penta-O-acetyl-β-D- galactopyranose (1.171 g, 3 mmol) in dry CH3CN (20 mL) was added to the mixture of 2-nitroimidazole (0.339 g, 3.0 mmol; triethylsilylated according to general procedure A) in dry CH3CN (4 mL, sonicated for 2 min) under argon. After the stirred mixture was cooled to 0 C, TfOTES (3.6 mL, 1.2 equiv, 1 M in dry 1,2-C2H4Cl2) was added, and stirring was continued for 1 h at 0 C and 1 h at rt. A saturated aq solution of NaHCO3 (20 mL) was added ,and the mixture was extracted with EtOAc (3 15 mL). The combined organic layers were washed with water (20 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash column chromatography (hexanes/EtOAc, 2:1; TLC, hexanes/EtOAc, 1:1, Rf 0.45) to give nucleoside β-2221a (1.219 g, 92%) as a gum: [α]2D0 +62.50 (c 1.48, acetone); IR (Si) νmax 1753, 1370, 1231,1094, 1064 cm 1 1 ; H NMR (400.1 MHz, CDCl3) δ 7.41 (d, J = 1.0 Hz, 1H), 7.16 (d, J = 1.0 Hz, 1H), 6.38 (d, J = 9.1 Hz, 1H), 5.51 (dd, J = 3.3, 1.0 Hz, 1H), 5.44 (dd, J = 10.1, 9.1 Hz, 1H), 5.33 (dd, J = 10.1, 3.3 Hz, 1H), 4.25 (ddd, J = 7.1, 5.8, 1.0 Hz, 1H), 4.14 (AB system, J = 11.4, 7.1, 5.8 Hz, 2H), 2.17 (s, 3H), 2.01 (s, 3H), 1.96 (s, 3H), 1.88 (s, 3H); 13C NMR (100.6 MHz, CDCl3) δ 170.3, 169.8, 169.6, 169.1, 144.5, 128.9, 122.1, 83.5, 74.2, 70.9, 68.7, 67.0, 61.1, 20.5 (2C), 20.4, 20.2. 1-α-(20,30-Di-O-acetyl-D-arabinofuranosyl)-2-nitroimida- zole (α-23). Nucleoside α-15 (0.231 g, 0.407 mmol) was desilylated by general procedure B. The crude product was purified by flash chroma- tography (at first hexanes/EtOAc, 1:1, Rf 0.08, and then 1:5) to give α- 23 (0.113 g, 84%) as a crystalline solid: mp 115 116 C (C2H4Cl2/i- Pr2O) (lit.26 semisolid mass); [α]2D0 5.6 (c 1.1, acetone); ;IRH(Sani)dν1m3Cax 3387, 2939, 1748, 1539, 1479, 1371, 1234, 1161, 1063 cm 1 1 NMR data agree with those of the literature.25 1-α-[20,30-Di-O-acetyl-50-O-(4-toluenesulfonyl)-D-ara- binofuranosyl]-2-nitroimidazole (α-7). α-23 (0.300 g, 0.91 mmol) was tosylated by general procedure C. The crude product was purified by flash chromatography (hexanes/EtOAc, 1:1, Rf 0.26) to give tosylate α-7 (0.420 g, 95%) as colorless plates: mp 102 103 C (CHCl3/i-Pr2O); [α]2D0 +39.3 (c 0.9, acetone);28 IR (Si) νmax 1750, 1540, 1477, 1368, 1232, 1191, 1178, 1096, 1052 cm 1; the 1H and 13C NMR data agree with those of the literature, except that a signal in the 13C NMR spectrum at 20.4 is replaced by one at 17.3.28 1-β- and 1-α-[1,2-Di-O-acetyl-3,5-O,O-(1,1,3,3-tetra- isopropyldisiloxanylidene)-D-ribofuranose (β- and α-24). D- Ribose (0.45 g, 3 mmol) was dissolved in dry pyridine (15 mL) under argon and cooled to 35 C. 1,3-Dichloro-1,1,3,3-tetraisopropyldisi- loxane (0.946, 0.96 mL) was added, and the mixture was stirred and allowed to slowly warm in the cooling bath to rt (18 h). Ac2O (1.5 mL) was added, and stirring was continued for another 6 h, before water (2 mL) was added. After 10 min the mixture was concentrated under reduced pressure. The residue was treated with water (20 mL) and EtOAc (20 mL). The organic phase was separated, and the aq one was extraceted with EtOAc (15 mL). The combined organic layers were washed (20 mL each) with water, 2 N HCl, water, and a saturated aq 8164 dx.doi.org/10.1021/jo200727k |J. Org. Chem. 2011, 76, 8159–8167