Reaction Steps
A reaction mixture containing the trans-D tosylate (7) (1.10 g, 2.00 mmol), N4-benzoylcytosine (0.475 g, 2.20 mmol), anhydrous K2CO3 (0.300 g, 2.20mmol) and 18-crown-6 (200 mg) in DMF (10 ml) was stirred at 70-80° C. under argon overnight. The white suspension was diluted with dichloromethane (75 ml), filtered through celite and the organic phase washed with water. Evaporation gave the crude product as an oil which was purified by column chromatography (SiO2, ethyl acetate). The more polar fractions (Rf 0.33) were combined and evaporated to give the N1-isomer (0.299 g, 25%) as a white foam. Recrystallisation from ethanol-water gave white crystals of N-tert-butoxycarbonyl-cis-4-(N4-benzoylcytosin-1-yl)-D-proline diphenylmethyl ester (11), m.p. 133-135° C., (Found C, 65.8; H, 6.5; N, 8.8%; C34H34N4O6.C2H5OH.H2O requires C, 65.6; H, 6.4; N, 8.5%), δH (200 MHz; CDCl3) 1.30 and 1.49 (9H, 2×s, Boc rotamers), 2.20 and 2.90 [2H, br m, CH2(3′)], 3.50-3.80 and 3.95-4.15 [2H, 2×br m, CH2(5′)], 4.45-4.70 [1H, br m, CH(2′)], 5.28 [1H, br m, CH(4′)], 6.87 (1H, s, CHPh2), 7.15-7.40 (10H, m, phenyl CH), 7.40-7.75 [5H, m, CH(5), CH(6) and benzoyl m- and p-CH], 7.89 (2H, d, J=7.4 Hz, benzoyl o-CH), 8.83 (1H, br s, NH); δC (50.28 MHz; CDCl3) 27.7 and 28.0 (Boc CH3 rotamers), 34.4 and 36.0 [CH2(3′) rotamers], 49.6 and 50.5 [CH2(5′) rotamers], 54.3 and 54.9 [CH(4′) rotamers], 57.6 [CH(2′)], 78.0 and 78.3 (CHPh2 rotamers), 81.3 (Boc C), 96.8 [CH(5)], 127.0-129.2 (aromatic CH), 133.4 (benzoyl C), 139.5 (aromatic C), 145.2 and 145.7 [CH(6) rotamers], 153.8 (Boc CO rotamers), 155.6 [C(2)], 162.0 [C(4)], 166.8 (benzoyl CO), 171.3 (ester CO); m/z (ES MS) 595 (M+H+, 100%); νmax (KBr)/cm−1 1743 (C═O), 1704s (C═O); λmax (CHCl3)/nm 266 (ε/dm3.mol−1.cm−1 8.9×104), 312 (3.4×104); [α]D23−13.6 (c=0.50, CHCl3).
