Beilstein J. Org. Chem. 2017, 13, 855–862.
DMSO-d6) δ 7.81 (d, J = 7.8 Hz, 1H), 7.90–7.58 (m, 2H), 7.45 [α]D25 −10.83 (c 0.23, CH3OH); 1H NMR (400 MHz, CDCl3) δ
(td, J = 7.2, 2.0 Hz, 1H ), 5.71 (d, J = 3.6 Hz, 1H), 5.34 (d, J = 7.95 (d, J = 7.9 Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.42 (t, J =
6.9 Hz, 1H), 4.56–4.50 (m, 2H), 4.22 (dd, J = 12.2, 6.1 Hz, 1H), 7.6 Hz, 1H), 7.29 (t, J = 7.7 Hz, 1H), 6.31 (d, J = 2.0 Hz, 1H),
4.05–4.01 (m, 1H), 3.86–3.81 (m, 1H), 2.45 (t, J = 6.9 Hz, 2H), 6.29 (d, J = 2.2 Hz, 1H), 6.19 (s, 1H), 5.64 (dd, J = 7.3, 4.9 Hz,
1.55–1.50 (m, 2H), 1.47–1.41 (m, 5H), 1.27 (s, 3H), 0.91 (t, J = 1H), 5.57 (d, J = 4.9 Hz, 1H), 4.72 (dd, J = 12.1, 3.1 Hz, 1H),
7.2 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 165.6, 133.8, 4.64–4.57 (m, 1H), 4.41 (dd, J = 12.2, 4.9 Hz, 1H), 3.80 (s, 3H),
132.0, 131.9, 129.8, 127.8, 123.3, 111.5, 103.5, 95.9, 78.9, 78.8, 3.76 (s, 3H), 2.47 (t, J = 7.1 Hz, 2H), 2.29 (s, 3H), 2.07 (s, 3H),
76.9, 71.3, 64.1, 30.1, 26.6, 26.3, 21.4, 18.6, 13.5; HRMS (ESI) 1.95 (s, 3H), 1.64–1.57 (m, 2H), 1.51–1.44 (m, 2H), 0.93 (t, J =
m/z: [M + Na]+ calcd for C21H26O6Na, 397.1627; found, 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 169.4, 169.2,
397.1608.
167.0, 165.8, 162.0, 158.9, 139.2, 134.5, 131.9, 131.4, 130.4,
127.2, 125.1, 114.7, 107.0, 98.4, 96.7, 96.3, 80.0, 79.1, 74.3,
Synthesis of 1,2-O-isopropylidene-3-O-(2,4-dimethoxy-6- 71.1, 63.9, 55.9, 55.5, 30.8, 22.2, 21.0, 20.7, 20.1, 19.6, 13.8;
methylbenzoyl)-5-O-(2-(hex-1-yn-1-yl)benzoyl)-α-D-ribofu- HRMS (ESI) m/z: [M + Na]+ calcd for C32H36O11Na,
ranose (15): To a solution of 14 (3.0 g, 8.0 mmol) in dry 619.2150; found, 619.2147. 16-α: Rf 0.17 (PE/EtOAc 4:1, v:v);
CH2Cl2 (25 mL) was added DMAP (97.88 mg, 0.8 mmol) and [α]D25 +10.20 (c 0.15, CH3OH); 1H NMR (400 MHz, CDCl3) δ
Et3N (1.05 g, 10.4 mmol). To the mixture benzoyl chloride 9 7.89 (dd, J = 7.9, 1.1 Hz, 1H), 7.52 (dd, J = 7.8, 1.0 Hz, 1H),
(2.15 g, 10 mmol) in dry CH2Cl2 (10 mL) was slowly added at 7.43 (td, J = 7.6, 1.4 Hz, 1H), 7.32 (td, J = 7.7, 1.3 Hz, 1H),
0 °C and stirred overnight at room temperature. The reaction 6.48 (d, J = 4.6 Hz, 1H), 6.33– 6.32 (m, 2H), 5.59 (dd, J = 6.8,
was quenched with methanol (5 mL) and evaporated to dryness 3.0 Hz, 1H), 5.40 (dd, J = 6.8, 4.6 Hz, 1H), 4.70–4.66 (m, 1H),
under reduced pressure. The obtained residue was dissolved in 4.65 (dd, J = 12.1, 3.0 Hz, 1H), 4.54 (dd, J = 12.1, 3.7 Hz, 1H),
CH2Cl2 (40 mL), washed with sat. NaHCO3 (40 mL × 2), brine 3.81 (s, 3H), 3.78 (s, 3H), 2.48 (t, J = 7.1 Hz, 2H), 2.36 (s, 3H),
(30 mL × 2), and dried over anhydrous MgSO4. The obtained 2.06–2.05 (m, 6H), 1.63–1.60 (m, 2H), 1.54–1.43 (m, 2H), 0.94
residue was purified by a silica gel column chromatography (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 169.8,
(PE/EtOAc 4:1, v:v) to afford 15 as colorless oil (3.3 g, 74%). 169.5, 167.4, 165.9, 161.9, 158.9, 138.7, 134.5, 131.9, 131.3,
Rf 0.46 (PE/EtOAc 3:1,v:v); [α]D25 +48.18 (c 0.22, CH3OH); 130.2, 127.4, 124.9, 115.3, 106.9, 96.6, 96.4, 94.3, 82.2, 79.1,
1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 7.8 Hz, 1H), 7.49 (d, 70.6, 70.4, 64.2, 56.0, 55.5, 30.8, 22.2, 21.2, 20.5, 20.2, 19.6,
J = 7.2 Hz, 1H), 7.41 (t, J = 7.4 Hz, 1H), 7.26 (t, J = 7.6 Hz, 13.8; HRMS (EI) m/z: [M + Na]+ calcd for C32H36O11Na,
1H), 6.30 (d, J = 9.7 Hz, 2H), 5.92 (d, J = 3.7 Hz, 1H), 5.03 (t, J 619.2150; found, 619.2150.
= 4.0 Hz, 1H), 4.94 (dd, J = 9.3, 4.8 Hz, 1H), 4.69 (dd, J = 12.2,
2.4 Hz, 1H), 4.56–4.47 (m, 1H), 4.40 (dd, J = 12.2, 5.4 Hz, 1H), Synthesis of 1-(2’-O-acetyl-3’-O-(2,4-dimethoxy-6-methyl-
3.79 (s, 3H), 3.76 (s, 3H), 2.47 (t, J = 7.0 Hz, 2H), 2.35 (s, 3H), benzoyl)-5’-O-(2-(hex-1-yn-1-yl)benzoyl)-β-D-ribo-fura-
1.63–1.57 (m, 2H), 1.55 (s, 3H), 1.47 (d, J = 7.8 Hz, 2H), 1.36 nosyl)uracil (17): To a suspension of uracil (0.24 g, 2.2 mmol)
(s, 3H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) in dry MeCN (15 mL) was added BSA (1.36 g, 6.7 mmol). The
δ 167.3, 166.0, 161.8, 158.8, 139.2, 134.4, 131.7, 131.3, 130.4, mixture was heated at 50 °C for 20 min. After cooled to room
127.1, 124.8, 115.1, 113.1, 106.8, 104.6, 96.4, 96.1, 79.1, 77.3, temperature, a solution of 16 (1.00 g, 1.7 mmol) in dry MeCN
75.6, 73.2, 63.4, 55.8, 55.4, 30.7, 26.6, 22.1, 20.1, 19.5, 13.7; (5 mL) along with TMSOTf (1.30 g, 5.9 mmol) were added to
HRMS (ESI) m/z: [M + Na]+ calcd for C31H36O9Na, 575.2257; the above reaction mixture at 0 °C. The solution was stirred for
found, 575.2293.
5 min before heating to 75 °C for 3–4 h. Then the reaction mix-
ture was poured into cold sat. NaHCO3 solution (30 mL). It was
Synthesis of 1,2-O-diacetyl-3-O-(2,4-dimethoxy-6-methyl- extracted with CH2Cl2 (50 mL). The combined organic layer
benzoyl)-5-O-(2-(hex-1-yn-1-yl)benzoyl)-D-ribofuranose was washed with sat. aq NaHCO3 (100 mL × 2), brine
(16): A solution of 15 (2.1 g, 3.8 mmol) in acetic acid (10 mL) (50 mL × 2), and dried with anhydrous Na2SO4. After filtration,
and Ac2O (1.94 g, 19.0 mmol) was added concentrated sulfuric the filtrate was evaporated under reduced pressure. The residue
acid (0.2 mL) dropwise over 10 min. After addition, the reac- was purified by silica gel column chromatography (DCM/
tion mixture was stirred at room temperature for 2 h. TLC CH3OH, 10:1) to give nucleoside 17 as a white solid (0.96 g,
detection showed the reaction was finished. The compound was 89%). Rf 0.43 (CH2Cl2/CH3OH 30:1,v:v); mp 69–70 °C; [α]D25
diluted with CH2Cl2 (80 mL) and washed with water −3.10 (c 0.28, CH3OH); 1H NMR (400 MHz, CDCl3) δ 9.53 (s,
(100 mL × 3), sat. NaHCO3 (100 mL × 3), brine (100 mL), and 1H), 7.88 (d, J = 7.4 Hz, 1H), 7.54 (d, J = 7.4 Hz, 1H), 7.46 (t, J
dried (anhydrous Na2SO4). The obtained residue was purified = 7.6 Hz, 1H), 7.40–7.33 (m, 2H), 6.33 (s, 2H,), 6.19 (d, J = 6.1
by flash column chromatography to afford 16 as colourless oil Hz, 1H), 5.67–5.64 (m, 1H), 5.52 (d, J = 8.1 Hz, 1H), 5.42 (t, J
(1.68 g, β:α 8:1, 74%). 16-β: Rf 0.30 (PE/EtOAc 4:1, v:v); = 5.9 Hz, 1H), 4.72 (dd, J = 12.4, 2.5 Hz, 1H), 4.64 (dd, J =
860