Reaction Steps
A solution of 80.2 mg (102 μmol) of compound 17, pyridine (25 μl, 3.0 eq.) and 4-nitrophenyl chloroformate (44.3 mg, 220 μmol) in dry tetrahydrofuran/dichloromethane was stirred under an Argon atmosphere at 0° C. for two hours and overnight at room temperature. The solution was evaporated in vacuo and the residual product was dissolved in dichloromethane. After washing the organic layer with brine and 0.5 N potassium bisulfate, the organic layer was dried over anhydrous sodium sulfate and concentrated to dryness. The resulting crude product was subjected to column chromatography (SiO2—CHCl3/MeOH 20/1) to obtain 61.9 mg (84%) of compound 18. M.P. 69–70° C.; 1H-NMR (300 MHz, CDCl3/CD3OD): δ 1.23 (d, 3H, 3J=7.0 Hz, CH3-Ala), 1.10–2.08 (m, 6H, 3 CH2-Lys), 3.04 (m, 1H, benzylic), 3.13 (m, 2H, N—CH2-Lys), 3.27 (bd, 1H, benzylic), 4.06 (m, 1H, Hα), 4.26 (m, 1H, Hα), 4.35–4.70 (m, 5H, Hα and Aloc), 5.04–5.47 (m, 4H, Aloc), 5.14 (s, 2H, benzylic-spacer), 5.24 (s, 2H, benzylic-spacer), 5.72 (m, 1H, Aloc), 5.90 (m, 1H, Aloc), 7.10–7.46 (m, 13H, aromatic), 7.65 (d, 2H, 3J=8.3 Hz, aromatic), 8.27 (d, 2H, 3J=9.1 Hz, aromatic-PNP) ppm; MS (FAB) m/e 952 (M+H)+, 974 (M+Na)+; C40H46O12 (.¼H2O) calculated C, 59.51%; H, 5.81%; N, 10.41%; measured C 59.52%; H, 5.54%; N, 10.12%.
