Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].CO[C:13](OC)([CH3:15])[CH3:14]>CC(C)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>[CH3:14][C:13]1([CH3:15])[O:4][C@@H:3]2[C@@H:5]([C@@H:7]([CH2:9][OH:10])[O:8][CH:2]2[OH:1])[O:6]1
Reactant: O=C[C@H](O)[C@H](O)[C@H](O)CO
Reactant: COC(C)(C)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Product: CC1(C)O[C@@H]2[C@@H](CO)OC(O)[C@@H]2O1
Temperature: 0 °C
Reaction time: 2 h
Yield: 90.4 %

Procedure:
A suspension of D-ribose (300 g, 1.99 mol) in acetone (3000 mL) was cooled to 0° C. and treated with p-toluenesulfonic acid (11.4 g, 0.059 mol) and 2,2-dimethoxypropane (268 mL, 2.19 mol). After stirred at room temperature for 2 h, the clear resulting mixture was neutralized with NaHCO3 (6.7 g), filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc:hexane=1:2) to afford 1 (342 g, 90%) as a colorless oil. 1H NMR (CDCl3) δ 5.62 (s, 1H), 4.83 (d, J=5.9 Hz, 1H), 4.73 (d, J=5.9 Hz, 1H), 4.41 (s, 1H), 3.72 (m, 2H), 1.48 (s, 3H), 1.32 (s, 3H); 13C NMR (CDCl3) δ 112.05, 102.61, 87.53, 86.60, 81.53, 63.37, 26.23, 24.58. 5-(tert-Butyldimethylsilyloxy)-2,3-isopropylidenedioxy-D-ribofuranose (2). A solution of 1 (320 g, 1.68 mol) in CH2Cl2 (3000 mL), tert-Butyldimethylsilyl chloride (304 g, 2.01 mol) and imidazole (172 g, 2.52 mol) were added at 0° C. After stirred for 4 h at room temperature, H2O (1000 mL) was added to the reaction mixture. The water layer was separated and the organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on a silica gel (EtOAc:hexane=1:20) to give 2 (415 g, 81%) as a colorless oil. 1NMR (CDCl3) δ 5.27 (d, J=11.7 Hz, 1H), 4.77 (d, J=11.8 Hz, 1H), 4.69 (d, J=5.9 Hz, 1H), 4.49 (d, J=5.9 Hz, 1H), 4.35 (s, 1H), 1.54 (s, 0.3H), 1.47 (s, 2.7H), 1.38 (s, 0.3H), 1.31 (s, 2.7H), 0.92 (s, 8H), 0.87(s, 1H), 0.16 (d, J=2.8 Hz, 0.6H), 0.13 (d, J=2.8 Hz, 5.4H); 13C NMR (CDCl3) δ 112.00, 103.59, 103.43, 97.94, 88.70, 87.98, 87.58, 86.94, 81.87, 81.73, 81.18, 79.39, 65.47, 64.78, 63.83, 26.44, 25.74, 25.51, 24.89, −5.72. (4R,5S)-1-{4-[2-(tert-Butyldimethylsilyloxy)-1-hydroxyethyl]-2,2-dimethyl-1,3-dioxolan-5-yl}-(S)-prop-2-en-1-ol (3). A solution of 2 (250 g 0.82 mol) in anhydrous tetrahydrofuran (1700 mL) was cooled to −78° C. and vinylmagnesium bromide (1M solution in tetrahydrofuran, 2.62 L, 2.62 mol) was added dropwise under −78° C. After addition was completed, the reaction mixture was allowed to stir at room temperature for 2 h. The reaction mixture was poured in to a mix of saturated NH4Cl (aq) and ether (1:2) (3 L). The organic and layer was separated and aqueous layer was extracted with ether (2 x 600 mL). The combined organic layers was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc:hexane=1:20) to give 3 (251 g, 92%) as colorless oil. [α]23D+6.86° (C 0.59, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.02 (m, 2H), 5.43 (d, J=17.2 Hz, 1H), 5.26 (d, J=10.4 Hz, 1H), 4.35 (bs, OH, D2O exchangeable, 1H), 4.31 (bs, 1H), 4.07 (m, 2H), 3.86 (m, 2H), 3.65 (dd, J=6.7 and 9.9 Hz, 1H), 3.36 (bs, OH, D2O exchangeable, 1H), 1.39 (s, 3H), 1.32(s, 3H), 0.91 (s, 9H), 0.10 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 137.31, 115.93, 108.65, 80.62, 76.53, 69.61, 69.22, 64.14, 27.86, 25.73, 25.29, −5.53; Anal. Calcd for C16H32O5Si: C, 57.79; H, 9.70. Found: C, 58.13; H, 9.80. (4R,5S)-1-[4-(1,2-dihydroxyethyl)-2,2-dimethyl-[1,3]dioxolan-5-yl]-(S)-prop-2-en-1-ol (4). Tetrabutylammonium fluoride (1 M solution in tetrahydrofuran, 1128 mL, 1.12 mol) was added to a solution of 3 (250 g, 0.75 mol) in tetrahydrofuran (1000 mL) and stirred at room temperature for 2 hr. The resulting brown mixture was concentrated in vacuo and the residue was purified by column chromatography on a silica gel (EtOAc:Hexane=2:1) to give 4 (161 g, 98%) as a white solid. mp 73-74° C.; [α]23D−31.33° (C. 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.03 (m, 1H), 5.40 (dd, J=0.8 and 17.2 Hz, 1H), 5.31 (dd, J=0.8 and 10.5 Hz, 1H), 4.34 (t, J=8.1 Hz, 1H), 4.16 (dd, J=5.4 and 9.4 Hz, 1H), 4.06 (dd, J=5.4 and 9.2 Hz, 1H), 3.95-3.87 (m, 1H D2O exchangeable, 3H), 2.15 (bs, OH, D2O exchangeable, 1H), 1.40 (s, 3H), 1.34(s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.64, 117.13, 79.98, 77.83, 69.31, 64.56, 27.96, 25.43; Anal. Calcd for C10H18O5.0.03 hexane: C, 55.37; H, 8.41. Found: C, 55.60; H, 8.31. (1S,2S,3S)-2,2-Dimethyl-6-vinyltetrahydrofuro[3,4,d]-1,3-dioxol-4-ol (5). A triol 4 (161 g, 737.6 mmol) in H2O (1600 mL) was cooled to 0° C. and NaIO4 (237 g, 1.106 mol) was added portion wise. After stirring at room temperature for 2 h, the reaction mixture was extracted with EtOAc (500 mL×3) and the extracts were dried over MgSO4, filtered, and concentrated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc:hexane=1:10) to give 5 (129 g, 94%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.01 (m, 0.8H), 5.79 (m, 0.2H), 5.50 (d, J=2.8 Hz, 0.8H), 5.43-5.16 (m, 2.2H), 4.70-4.56 (m, 3H), 3.93 (d, J=10.4 Hz, 0.2H), 2.66 (d, J=2.8 Hz, 0.8H), 1.59 (s, 0.6H), 1.51 (s, 2.4H), 1.39 (s, 0.6H), 1.33 (s, 2.4H); 19C NMR (100 MHz, CDCl3) δ 137.94, 134.43, 117.31, 117.01, 114.32, 112.45, 102.95, 102.91, 96.15, 88.54, 86.62, 84.73, 80.58, 79.01, 26.42, 26.19, 24.95; Anal. Calcd for C9H14O4: C, 58.05 H, 7.58. Found: C, 58.38; H, 7.74. (1S,2S,3R)-1-(2,2-Dimethyl-5-vinyl[1,3]dioxolan-4-yl)-(S)-prop-2-en-1-ol (6). A suspension of methyltriphenylphosphonium bromide (562 g, 1.55 mol) in tetrahedrofuran (1000 mL) was cooled to 0° C. and KO′Bu (210 g, 1.86 mol) was added portion wise under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 h and then recooled to 0° C. A solution of lactol 5 (116 g, 0.622 mol) in tetrahydrofuran (300 mL) was added to the resulting reaction mixture at 0° C. The mixture was stirred for 6 h at rt, diethyl ether (1500 mL) was added to the reaction mixture, and washed with H2O (500 mL) and brine (500 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc:hexane=1:10) to give 6 (101 g, 88%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.05 (m, 2H), 5.36 (m, 4H), 4.70 (t, J=6.8 Hz, 1H), 4.19 (m, 1H), 4.04 (dd, J=6.8 and 7.6 Hz, 1H), 1.79 (bs, 1H), 1.50 (s, 3H), 1.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.89, 134.24, 118.47, 116.63, 109.06, 80.72, 78.88, 71.20, 27.80, 25.46; Anal. Calcd for C10H16O3: C, 65.19; H, 8.75. Found: C, 65.34; H, 8.43. (4R,5R)-4.5-O-Isopropylidene-cyclopent-2-enone (7). To a solution of first generation Grubb's catalyst (4.198 g, 5.10 mmol, 1 mol%) in anhydrous CH2C12 (300 mL), diene 6 (94 g, 510.2 mmol) in anhydrous CH2Cl2 (1500 mL) was added and stirred for 7 h at rt under nitrogen atmosphere. To the mixture 4 Å molecular sieves (94 g), pyridinium dichromate (288 g, 765.3 mmol) and acetic acid (1.53 mL, 25.5 mmol) were added. The resulting brown mixture was stirred at rt for 12 h and filtered through a celite pad with CH2Cl2. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on a silica gel (EtOAc:hexane=1:10) to give 7 (72 g, 91%) as a white crystalline solid. mp 68.5-70.3° C.; [α]23D−69.3 (c 0.60, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.61 (dd, J=2.4, 6.0 Hz, 1H), 6.22 (d, J=6.0 Hz, 1H), 5.28 (dd, J=2.4, 5.6 Hz, 1H), 4.47 (d, J=5.6 Hz, 1H), 1.42 (s, 3H), 1.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.56, 134.64, 115.36, 78.58, 76.49, 27.40, 26.14; Anal. Calcd for C10 H10O3: C, 62.33; H, 6.54. Found: C, 62.15; H, 6.52. (1S,2S,3R,4R)-4-(tert-Butoxymethyl)-2,3-(isopropylidenedioxy)-1-cyclopentanone (8). A suspension of potassium tert-butoxide (41.6 g, 0.35 mol) in anhydrous tert-butylmethyl ether (1200 ml) was cooled to −78° C. under nitrogen. The well stirring mixture was treated with sec-butyllithium (1.6 M solution in hexane, 250 mL, 0.35 mol) over 20 min. After the mixture was stirred for 2 h at −78° C., a solution of LiBr (61 g, 0.70 mol) in THF (450 mL) was added drop wise over 20 min at −78° C. and the resulting solution was stirred at −15° C. for 30 min. Upon recooling to −78° C., a solution of CuBr.SMe2 (37.3 g, 0.14 mol) in diisopropyl sulfide (150 mL) was added drop wise over 20 min. The resulting viscous dark solution was stirred for 1 h at −78° C. and treated with a solution of enone 7 (18.1 g, 0.117 mol) in THF (150 mL) over 15 min. The reaction mixture was allowed to warm to −30° C. over 15 min and stirred for 30 min at −30° C. The mixture was recooled to −78° C. and 1:1 acetic acid-methanol (415 mL) was added and the mixture poured in to 3000 mL of NH4Cl/NH4OH (1:1). After removal of the aqueous layer, the organic layer was washed with a saturated aqueous NH4Cl solution (300 mL×2) and brine (400 mL). The organic phase was dried (Na2SO4), filtered, concentrated and purified through silica gel column chromatography with 5% EtOAc in hexanes to give 8 (25 g, 88%) as a white solid. NMR (500 MHz, CDCl3) δ 1.10 (s, 9H), 1.34 (s, 3H), 1.43 (s, 3H), 2.06 (d, J=22 Hz, 1H), 2.55 (d, J=12.5 Hz, 1H), 2.72 (dd, J=11, 22 Hz, 1H), 3.34 (dd, J=3.5, 10.5 Hz, 1H), 3.52 (dd, J=3.5, 10.5 Hz, 1H), 4.22 (d, J=7 Hz, 1H), 4.61 (d, J=7 Hz, 1H); Anal. Calcd for C13H22O4: C, 64.44; H, 9.15. Found: C, 64.19; H, 9.14. (1S,2S,3R,4R)-4-(tert-Butoxymethyl)-2,3-(isopropylidenedioxy)-cyclopentan-1-ol (9). A solution of compound 8 (25 g, 0.103 mol) and CeCl3.7H2O (49.96 g, 0.134 mol) in MeOH (200 mL) was stirred 15 min at rt. The mixture was cooled to −78° C., NaBH4 (5.07 g, 0.134 mol) was slowly added and allowed the mix warm to 0° C. After stirring 1 h at 0° C., cold water (20 mL) was added and the methanol was removed under reduced pressure. The residue was extracted with EtOAc (2×600 mL), the combined organic phase was washed with brine (500 mL) and then dried over anhydrous Na2SO4, and filtered. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (15% EtOAc:hexane) to give 9 (24 g, 95%) as a syrup. [α]26D−16.95 (c 1.59, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.13 (s, 9H), 1.34 (s, 3H), 1.48 (s, 3H), 1.83 (m, 2H), 2.19 (m, 1H), 2.44 (d, J=9.0 Hz, 1H, D2O exchangeable), 3.20 (dd, J=4.5, 8.8 Hz, 1H), 3.31 (dd, J=4.5, 8.8 Hz, 1H), 4.23 (m, 1H), 4.44 (m, 2H); Anal. Calcd for C13H24O4; C, 63.91; H, 9.90. Found: C, 64.09; H, 9.87. (1S,2S,3R,4R)-4-(tert-Butoxymethyl)-2,3-(isopropylidenedioxy)-1-(methylsulfonyloxy)-cyclopentane (10). A miture of compound 9 (22 g, 90.04 mmol) and triethylamine (37.4 mL, 270.14 mmol) in CH2Cl2(400 mL), methane sulfonyl chloride (10.41 mL, 135.07 mmol) was added drop wise at 0° C. After stirring for 1 h at 0° C., the reaction mixture was quenched with cold water (300 mL) and extracted with CH2Cl2 (2×500 mL). The combined organic layers were washed with brine (400 mL) and dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified using column chromatography with EtoAc:hexane (1:1) to give 10 (quantitative yield) as a colorless oil. (1R,2S,3R,4R)-1-Azido-4-(tert-butoxymethyl)-2,3-(isopropylidenedioxy)-cyclopentane (11). A solution of 10 (30 g, 93.04 mmol) in dry DMF (400 mL) in the presence of sodium azide (60.49 g, 930.4 mmol) was heated at 140° C. for 5 h with stirring. After cooling to room temperature, the reaction mixture was filtered, and the filtrate was concentrated to dryness. The residue was diluted with EtOAc (500 mL), washed with water (2×300 mL) and brine (200 mL). The organic layer was dried over Na2SO4, filtered and concentrated to dryness. The resulting oil was purified by silica gel column chromatography (4% EtOAc in hexane) to give 11 (22.2 g, 89%) as a colorless oil. [α]26D−46.940 (c 1.11, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.18 (s, 9H), 1.30 (s, 3H), 1.46 (s, 3H), 1.71 (m, 1H), 2.29 (m, 2H), 3.29 (dd, J=6.7, 8.8 Hz, 1H), 3.37 (dd, J=7.0, 8.8 Hz, 1H), 3.96 (m, 1H), 4.40 (dd, J=2.3, 6.1 Hz, 1H), 4.48 (dd, J=2.0, 6.1 Hz, 1H); Anal. Calcd for C13H23N3O3.0.13EtOAc: C, 57.95; H, 8.65; N, 14.99. Found: C, 58.25; H, 8.71; N, 14.76. (1R,2S,3R,4R)-4-(tert-Butoxymethyl)-2,3-(isopropylidenedioxy)-1-cyclopentanamine (12). A suspension of compound 11 (20 g) and 10% Pd/C (5.0 g) in absolute EtOH (250 mL) was shaken under 35 psi of H2 for 5 h. The reaction mixture was filtered and the filtrate was evaporated to give crude 12 (quantitative yield) which was used for next step without further purification. 1H NMR (400 MHz, CDCl3) δ 1.18 (s, 9H), 1.28 (s, 3H), 1.36 (m, 1H), 1.45 (s, 3H), 1.89 (br s, 2H, NH2), 2.24-2.36 (m, 2H), 3.34-3.43 (m, 3H), 4.21 (dd, J=2.6, 6.2 Hz, 1H), 4.48 (dd, J=2.8, 6.2 Hz, 1H); Anal. Calcd for C13H25NO3.0.16H2O: C, 63.41; H, 10.37; N, 5.69. Found: C, 63.09; H, 10.16; N, 5.59. N-{[(1R,2S,3R,4R)-4-(tert-Butoxymethyl)-2,3-(isopropylidenedioxy)-cyclopentyl]-aminocarbonyl}-3-methoxy-2-propenamide (13). A solution of β-methoxy acrylic acid in a mixture of CH2Cl2: benzene (2:1) (600 mL) was cooled to 0° C., then anhydrous DMF (1.2 mL) was added followed by oxalyl chloride (90 mL) was added at 0° C. under nitrogen atmosphere. The mix was stirred at 0° C. for 1 h and the solution was concentrated under reduced pressure to give the crude β-methoxy acryloyl chloride. Silver cyanate (77 g) was added to a solution of above obtained crude β-methoxy acryloyl chloride in anhydrous benzene (300 mL). The resulting mixture was heated under reflux for 1 h and allowed to cool to room temperature. After the solid phase had settled, the supernatant solution was contained with β-methoxy acryloyl isocyanate was added during 15 min to a solution of amine 12 (18 g) in anhydrous DMF (50 mL) at −15 to −20° C. under nitrogen. The reaction mixture was stirred for 2 h at −15° C. and then for 10 h at room temperature under nitrogen. The solvent was removed under reduced pressure and purified using silica gel column chromatography to afford 13 (19.8 g, 72%) as a solid. [α]27D−26.62 (c 0.57, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.17 (s, 9H), 1.28 (s, 3H), 1.47 (s, 3H), 1.58 (m, 1H), 2.28 (m, 1H), 2.36-2.43 (m, 1H), 3.33-3.42 (m, 2H), 3.73 (s, 1H), 4.20 (m, 1H), 4.45 (m, 2H), 5.35 (d, J=12.3 Hz, 1H), 7.67 (d, J=12.3 Hz, 1H), 8.72 (br s, 1H, NH), 9.35 (br s, 1H, NH); Anal. Calcd for C,8H30N2O6: C, 58.36; H, 8.16; N, 7.56. Found: C, 58.28; H, 8.13; N, 7.60. (1 R,2S,3R,4R)-1-[4-(tert-Butoxymethyl)-2,3-(isopropylidenedioxy)-cyclopentan-1-yl]-uracl (14). Compound 13 (18 g, 11.34 mmol) was dissolved in ethanol (80 mL), dioxane (60 mL) and ammonium hydroxide (30%, 80 mL). The reaction mixture was heated at 100° C. in a steel bomb for 20 h. After cooling, the solution was evaporated to dryness. The residue was purified by silica gel column chromatography (50% EtOAc in hexane) to give 14 (14 g, 85%) as a white foam. [α]27D−41.53 (c 0.88, CHCl3); UV (MeOH) λmax 266.0 nm; 1H NMR (400 MHz, CDCl3) δ 1.19 (s, 9H), 1.30 (s, 3H), 1.54 (s, 3H), 1.97 (m, 1H), 2.32-2.41 (m, 2H), 3.43-3.50 (m, 2H), 4.48 (dd, J=4.1, 6.5 Hz, 1H), 4.65-4.75 (m, 2H), 5.72 (d, J=8.0 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 8.63 (br s, 1H, NH); Anal. Calcd for C17H26N2O5: C, 60.34; H, 7.74; N, 8.28. Found: C, 60.06; H, 7.70; N, 8.14. (1R,2S,3R,4R)-1-[4-(tert-Butoxymethyl)-2,3-(isopropylidenedioxy)-cyclopentan-1-yl]-cytosine (15). A mixture of 14 (8 g, 23.6 mmol) and 4-dimethylamino-pyridine (5.78 g, 47.3 mmol) in anhydrous acetonitrile (250 mL), triethylamine (6.59 mL, 47.3 mmol) followed by 2,4,6-triisopropylbenzenesulfonyl chloride (14.33 g, 47.3 mmol) was added at rt under nitrogen. After being stirred for 12 h, NH4OH (30%, 200 mL) was added and stirred for 5 hours. The mixture was diluted with chloroform and washed with saturated aqueous NH4Cl (3×600 mL) solution and followed by washed with water (3×600 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified using silica gel column chromatography (CH2Cl2:MeOH=96:4) to give 15 (6.22 g, 78%) as a solid. UV (MeOH) λmax 275.0 nm; 1H NMR (500 MHz, DMSO-d6) 8 1.14 (s, 9H), 1.22 (s, 3H), 1.44 (s, 3H), 1.80 (m, 1H), 2.10 (m, 2H), 3.30 (dd, J=6, 9 Hz, 1H), 3.40 (d, J=5.5, 9.5 Hz, 1H), 4.38 (dd, J=5, 7 Hz, 1H), 4.60 (m, 1H), 4.75 (dd, J=5, 6.5 Hz, 1H), 5.71 (d, J=7.5 Hz, 1H), 7.13 (brs, 1H), 7.22 (brs, 1H), 7.70 (d, J=7.5 Hz, 1H); Anal. Calcd for C17H27N3O4: C, 60.51; H, 8.07; N, 12.45. Found: C 60.42; H 8.03; N 12.45. (1R,2S,3R,4R)-1-[2,3-Dihydroxy-4-(hydroxymethyl)-cyclopentan-1-yl]cytosine (16). Compound 15 (5.5 g) was dissolved in CF3CO2H/H2O (2:1) (150 mL) and heated to 70° C. for 4 h. The solution was then concentrated under reduced pressure and coevaporated three times with methanol (3×200 mL). The residue was dissolved in water (300 mL) and washed with CH2Cl2 (4×100 mL). The water layer was concentrated under vacuum and the residue was dissolved in methanol and neutralized with IRA-400 (OH) basic resin. The resin was filtered, washed with methanol and the filtrate was concentrated under reduced pressure to give 16 (2.75 g, 82%) as a white solid. mp 214° C.; [α]27D−74.5 (c 0.52, H2O); UV (H2O) λmax 275.0 nm (pH 7), 285 (pH 2), 275 (pH 11); 1H NMR (500 MHz, DMSO-d6) δ 1.23 (m, 1H), 1.94 (m, 1H), 2.01 (m, 1H), 3.42 (m, 2H), 3.80 (dd, J=4.5, 9.0 Hz, 1H), 4.01 (m, 1H), 4.54 (d, J=4.5 Hz, 1H), 4.59 (q, 1H), 4.65 (t, J=5.0 Hz, 1H), 4.72 (d, J=7 Hz, 1H), 5.69 (d, J=7.5 Hz, 1H), 6.96 (brs, 1H), 7.01 (brs, 1H) 7.60 (d, J=7.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 165.7, 156.6, 143.8, 93.8, 73.8, 72.1, 63.4, 61.7, 45.4, 29.0; Anal. Calcd for C10H15N3O4: C, 49.77; H, 6.27; N, 17.42. Found: C 49.67; H 6.31; N 17.43. (1R,2S,3R,4R)-1-[2,3,Diacetoxy-4-(acetoxymethyl)-cyclopentan-1-yl]uracil (18). Compound 14 (5.7 g) was dissolved in CF3CO2H/H2O (2:1) (150 mL) and heated to 70° C. for 4 h. The solution was then concentrated under reduced pressure and coevaporated three times with methanol (3×200 mL). The residue containing 17 was dried under vacuum for overnight and it is used for next step directly. To a stirring solution of compound 17 (4.08, 16.85 mmol) in acetonitrile (100 mL), triethylamine (9.34 mL, 67.43 mmol), DMAP (41 mg, 0.33 mmol) fallowed by Ac2O (6.38 mL) were added at rt and stirred for 30 min. To mixture methanol (5 mL) was added and stirred for 10 min. The solvent was evaporated by vacuum to obtain white crude product. This was purified using silica gel column chromatography (EtOAc:Hexane=1:1) to give 18 (5.58 g, 90%) as a foam. 1H NMR (500 MHz, CDCl3) δ 1.73 (m, 1H), 2.04 (s, 3H), 2.10 (s, 6H), 2.39 (m, 1H), 2.52 (m, 1H), 2.51 (m, 2H), 4.79 (q, 1H), 5.24 (d, J=5 Hz, 1H), 5.43 (t, J=8 Hz, 1H), 5.77 (d, J=6 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 9.35 (s, 1H); 13 C NMR (500 MHz, CDCl3) δ 170.8, 170.1, 169.8, 163.0, 150.7, 141.7, 103.0, 73.1, 72.0, 64.2, 60.8, 40.0, 27.7, 20.8, 20.7, 20.6; HRMS-ESI (m/z): (M+H)+ calcd for C16H20N2O8, 369.1299; found, 369.1298. (1R,2S,3R,4R)-1-[2,3,Diacetoxy-4-(acetoxymethyl)-cyclopentan-1-yl]-5-fluorouracil (19) To a mixture of 18 (1.92 g, 5.21 mmol), selectfluor (2.03 g, 5.73 mmol) in acetonitrile (50 mL), AcOH (4 mL) was added at rt and stirred at 95° C. for 3 h. The mixture was diluted with ethyl acetate (200 mL), washed with H2O (100 mL) and saturated NaHCO3 solution (2×100 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure and dried over night with high vacuum. The crude residue was treated with Et3N (100 mL) and stirred at 95° C. for 3 h. The solvent was evaporated and purified using silica gel column chromatography (EtOAc:hexane=4:6) to give 19 (1.44 g, 72%) as a white foam. 1H NMR (500 MHz, CDCl3) δ 1.71 (m, 1H), 2.05 (s, 3H), 2.10 (s, 3H), 2.12 (s, 3H), 2.39 (m, 1H), 2.52 (m, 1H), 2.51 (m, 2H), 4.17 (dd, J=5.5, 12 Hz, 1H), 4.21 (dd, J=5.5, 12 Hz, 1H), 4.82 (q, 1H), 5.21 (t, J=6 Hz, 1H), 5.38 (m, 1H), 7.33 (d, J=6 Hz, 1H), 9.21 (s, 1H); 19F NMR (CDCl3, 500 MHz) δ-164; HRMS-ESI (m/z): (M+H)+ calcd for C16H19FN2O8, 387.1204; found, 387.1208. (1R,2S,3R,4R)-1-[2,3-Dihydroxy-4-(hydroxymethyl)-cyclopentan-1-yl]-5-fluorocytosine (20). A mixture of 19 (3.5 g, 9.06 mmol) and 4-dimethylamino-pyridine (2.21 g, 18.13 mmol) in anhydrous acetonitrile (100 mL), triethylamine (2.5 mL, 18.13 mmol) followed by 2,4,6-triisopropylbenzenesulfonyl chloride (5.49 g, 18.13 mmol) was added at rt under nitrogen. After being stirred for 12 h, NH4OH (30%, 150 mL) was added and stirred for 5 hours. The mix was concentrated under vacuum and the residue was purified using amine functionalized silica gel column chromatography (CH2Cl2:MeOH=5:1) fallowed by C18 silica gel chromatography (water:methanol=8:2) to give 20 (1.77 g, 76%) as a foam. UV (H2O) λmax 284 nm (pH 7), 293 nm (pH 2), 284 nm (pH 11); 1H NMR (500 MHz, DMSO-d6) δ 1.21 (m, 1H), 1.92 (m, 1H), 2.01 (m, 1H), 3.42 (m, 2H), 3.72 (q, 1H), 3.99 (m, 1H), 4.54 (d, J=4.5 Hz, 1H), 4.59 (q, 1H), 4.65 (t, J=5.5 Hz, 1H), 4.76 (d, J=6.5 Hz, 1H), 7.36 (brs, 1H), 7.60 (brs, 1H) 7.96 (d, J=7.5 Hz, 1H); HRMS-ESI (m/z): (M+H)+ calcd for C17H14FN3O4, 260.1047; found, 260.1044. Biological Data H5N1 Data