Ribofuranose, 1-acetate 2,3,5-tribenzoate

This compound is prepared from L-ribose according to Recondo and Rinderknecht (loc. cit.) who prepared 1-O-acetyl-2, 3, 5-tri-O-benzoyl-β-D-ribofuranose (1, RThis fulvous oil compound was dissolved in acetic acid (160 mL) and acetic anhydride (40.0 mL, 0.411 mol). The mixture was cooled to 0 °C before slowly adding concentrated sulfuric acid (25.0 mL, 0.469 mol). After dropping, the reaction was stirred at ambient temperature overnight. The reaction mixture was poured into water (200 mL) and neutralized with sodium acetate (40 g) and then extracted with chloroform (4 .x. 50 mL). The combined organic layer was washed with brine, dried over NaSynthesis of 1-O-acetyl-2, 3, 5-tri-O-benzoyl-β-L-ribofuranose The oil was dissolved in acetic anhydride (560 mL; Fluka; ref 45830) and acetic acid (240 mL; P. A. carlo erba; ref 20104298). The solution was, after the dropwise addition of concentrated sulphuric acid (80 mL), kept in the cold (+4 C.) under mechanical stirring for 10 h. The solution was then poured on ice (about 10 liters) under continued stirring. The mixture (oily compound in water) was filtered on a Cellite bed. The resulting gummy solid on the cellite bed was washed with water (3*3 liters) and then dissolved in dichloromethane (2.5 liters; P. A. Merck; ref 1.06050.6025). The organic phase was washed with 5% NaHCO3 (1 liter) and water (2*2 liters), dried over sodium sulfate, filtered and evaporated to give a gummy solid 143, which was crystallized from ethanol 95 (Prolabo; ref 20823.293) to yield 225 g of product (44%): mp 129-130 C (EtOH 95) (literature reference reported by Recondo, E. F., and Rinderknecht, H. 'Eine neue, Einfache Synthese des 1-O-Acetyl-2, 3, 5-Tri-O-beta-D-Ribofuranosides' Helv. Chim. Acta, 1959, 1171-1173 indicate a mp 130-131 C.); 1H NMR (200 MHz, CDCl3): delta8.09-7.87 (m, 6H, HArom), 7.62-7.31 (m, 9H, HArom) 6.43 (s, 1H, H1), 5.91 (dd, 1H, H3, J3, 4 6.7 Hz; J3, 2 4.9 Hz), 5.79 (pd, 1H, H2, J2, 3 4, 9 Hz; J1, 2<1), 4, 78 (m, 2H, H4 and H5), 4, 51 (dd, 1H, H5, J5, 5'13, 1 Hz, J5', 4 5, 5 Hz), 2, 00 (s, 3H, CH3CO); (identical to commercial 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofaranose), Mass analysis (FAB+, GT) m/z 445 (M-OAc)+, Elemental analysis C28H24O9 Calculated C 66.66 H 4.79; found C H.EXAMPLE 3 Preparation of 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-L-ribofuranose (12) 201 g (0.717 mole) of the compound (8) dissolved in 1000 ml of 4% trifluoroacetic acid (CF3COOH) was refluxed until the starting material (ca. 1 hour) and the intermediate (1-O-benzyl derivative) had disappeared (ca. 4-8 hours). The reaction mixture was cooled to room temperature and washed with dichloromethane (4*500 ml) to remove benzyl alcohol. The aqueous layer thereby obtained was evaporated in vacuo and coevaporated with toluene (2*200 ml) to yield the compound (9) in the form of a yellowish syrup, which was completely dried under high vacuum to remove a trace amount of water. The compound (9) was dissolved in 2000 ml of methanol and 15.8 g (0.43 mole) of HCl (gas) was bubbled into the mixture at room temperature. The mixture thereby obtained was stirred at room temperature for 2 hours, neutralized with 183 ml of pyridine and concentrated in vacuo at 30-35 C. to give a yellowish syrup, which was in turn coevaporated with pyridine to yield the compound (10) in the form of a yellowish syrup. The compound (10) was dissolved in 800 ml of pyridine and 212 ml of benzoyl chloride was added dropwise to the mixture at 0 C. The mixture was stirred at room temperature for 8 hours. After the reaction had gone almost to completion, the mixture was heated at 45 C. for 1.5 hour. The mixture was cooled to room temperature and ice was added to remove the remaining benzoyl chloride. Pyridine was evaporated from the mixture at 35-40 C. until the mixture occupied half of its initial volume. The residue was dissolved in 1500 ml of ethyl acetate, which was washed in succession with 500 ml of cold water, 576 ml of cold 3N H2SO4, 500 ml of aqueous sodium bicarbonate (*2), and 500 ml of brine, in that order. The organic layer was dried over MgSO4 and activated carbon, filtered through a silica gel (2-20mu) pad and evaporated to obtain the compound (11) in the form of a yellowish syrup. To a mixture of the compound (11) dissolved in 144 ml (2.52 mole) of acetic acid and 334 ml (3.54 mole) of acetic anhydride, 48 ml (0.9 mole) of c-H2SO4 was slowly added dropwise at 0 C., during which crystallization occurred. The mixture was brought to room temperature and kept in a refrigerator overnight. The mixture was poured into 700 ml of an ice-water mixture, filtered and the filter cake was washed twice with cold water. The solid was dissolved in 2000 ml of ethyl acetate, which was washed in succession with 500 ml of water, 500 ml of saturated sodium bicarbonate and 500 ml of brine. The organic layer was dried over MgSO4 and activated carbon and the resulting mixture was filtered through a silica gel (2-20mu) pad. The solvent was removed and the residue was recrystallized from methanol to obtain 144.7 g (Yield: 40% from the compound (8)) of the compound (12) in the form of a white solid. m.p.: 124-125 C. [a]25D=-22.1 (c 1, pyridine) 1H NMR(CDCl3) delta (ppm): 8.90-7.32(m, 15H, Ar-H), 6.43(s, 1H, H-1), 5.91(dd, 1H, H-3, J=4), 5.79(d, 1H, H-2, J=8), 4.81-4.76(m, 2H, H-4 and H-5), 4.54-4.49(m, 1H, H-5), 2.00(s, 3H, CH3COO)Analyses For 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-L-ribofuranose 143 mp 129-130 C. (EtOH 95) (lit.(1) mp 130-131 C.) 1H NMR (200 MHz, CDCl3): delta8.09-7.87 (m, 6H, HArom), 7.62-7.31 (m, 9H, HArom) 6.43 (s, 1H, H1), 5.91 (dd, 1H, H3, J3, 4 6.7 Hz; J3, 2 4.9 Hz), 5.79 pd, 1H, H2, J2, 3 4, 9 Hz; J1, 2<1), 4.78 (m, 2H, H4 and H5), 4, 51 (dd, 1H, H5, J5, 5' 13, 1 Hz, J5', 4 5, 5 Hz), 2, 00 (s, 3H, CH3CO); (identical to commercial 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose) Mass analysis (FAB+, GT) m/z 445 (M-OAc)+Analyses for 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-L-ribofuranose 143 mp 129-130 C. (EtOH 95) (lit.(1) mp 130-131 C.) 1H NMR (200 MHz, CDCl3): delta8.09-7.87 (m, 6H, HArom), 7.62-7.31 (m, 9H, HArom) 6.43 (s, 1H, H1), 5.91 (dd, 1H, H3, J3, 4 6.7 Hz; J3, 2 4.9 Hz), 5.79 (pd, 1H, H2, J2, 3 4.9 Hz; J1, 2<1), 4.78 (m, 2H, H4 and H5), 4.51 (dd, 1H, H5, J5, 5' 13.1 Hz, J5', 4 5.5 Hz), 2.00 (s, 3H, CH3CO); (identical to commercial 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose) Mass analysis (FAB+, GT) m/z 445 (M-OAc)+