Methanol → 2',3'-Di-O-acetyl-5'-deoxy-5-fluoro-N4-(3,7,11,15-Tetramethyl-hexadecyl oxycarbonyl)cytidine

関与物質

反応手順

To the ice-cooled solution containing 2′,3′-Di-O-acetyl-5′-deoxy-5-fluoroocytidine (5) (9.76 g, 29.64 mmol) in dry CH2Cl2 (40 ml) and anhydrous pyridine (5 ml), phytanyl chloroformate (12 g, 33 mmol) (6a) was added dropwise in order to keep the low reaction temperature. After stirring the mixture for overnight at room temperature, MeOH (1.3 ml) was added in one portion to stop the reaction. The mixture was evaporated to a syrup mass under reduced pressure. To this residue, diethyl ether (50 ml) was added and the suspension was stirred for 30 min at room temperature. The insoluble precipitate was filtered through a glass filter. The precipitate was washed with 30 ml of diethyl ether. The filtrate and the washings were collected, dried over anhydrous Na2SO4, and evaporated to dryness. The crude target compound was further purified using silica column chromatography CH2Cl2:MeOH=5:1 to give 2′,3′-Di-O-acetyl-5′-deoxy-5-fluoro-N4-(phytanyloxycarbonyl)cytidine (16.7 g, 84.1%) (7a). 1H NMR in CDCl3: δ0.83, 0.85, 0.86, 0.88 (4s, each 3H, CH3), 0.91 (d, 3H, J=6.6 Hz, CH3), 0.96-1.88 (m, 24H, CH2+CH), 1.47 (d, 3H, J=6.6 Hz, H-5), 2.10, 2.12 (2s, each 3H, OMe), 4.13-4.37 (m, 3H, H-4+CH2OC═ONH), 5.01 (t, 1H, J=5.4 Hz, H-2), 5.29 (t, 1H, J=5.8 Hz, H-3), 5.96 (d, 1H, J=3.8 Hz, H-1), 7.39 (br s, 1H, N—CH═C—F).

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