Reaction Steps
DMAP (6.2 mg, 0.05 mmol) and DIC (0.16 mL, 1.01 mmol) were added to a stirred solution of O-tert-butyl-N-fluorenylmethoxycarbonyl-L-serine 9 (0.39 g, 0.60 mmol) in CH2Cl2 (3 ml). After 1 h, the carboxylic acid derivative 22 (0.41 g, 0.50 mmol) was added and the reaction was stirred for 5-9 h until no further conversion of the starting material could be detected by TLC analysis. The reaction mixture was diluted with CH2Cl2 (20 mL), washed with water (2×10 mL) and brine (10 mL). The organic phase was separated, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (ethyl acetate-hexane gradient elution) to afford the title compound 23 (0.47 g, 0.40 mmol) as a colorless amorphous solid in 79% yield. Analytical data for 23: Rf=0.43 (ethyl acetate/hexane, 3/7, v/v); [α]D24+36.1° (c=1.0, CHCl3); 1H NMR (300 MHz, CDCl3): δ, 0.88 (t, 6H, 2×CH3), 1.17 (m, 40H, 20×CH2), 1.38 (s, 9H, t-Bu), 1.54 (m, 4H, 2×CH2), 2.53 (m, 4H, 2×CH2), 3.18 (dd, 1H, J2,3=9.7 Hz, H-2), 3.26 (s, 3H, OCH3), 3.28 (m, 1H, H-4), 3.42-3.66 (m, 5H, H-3, 5, OCH2, OCH2a), 3.67 (s, 3H, OCH3), 3.79 (m, 1H, OCH2b), 4.11-4.46 (m, 8H, H-6a, 6b, ½CH2Ph, Ser-CαH, Ser-CβH2, CH2Fmoc), 4.66 (d, 1H, J1,2=3.3 Hz, H-1), 4.71 (d, 1H, J2=10.5 Hz, ½CH2Ph), 5.71 (d, 1H, JNH,CH=8.1 Hz, Ser-NH), 6.75-7.64 (m, 12H, aromatic) ppm; 13C NMR (75 MHz, CDCl3): δ, 14.2, 22.8, 26.1, 26.4, 28.0, 28.9, 29.5, 29.6, 29.7, 29.8, 30.2, 30.7, 32.0, 47.0, 54.0, 55.2, 55.3, 64.7, 67.3, 68.6, 71.8, 73.8, 74.6, 80.8, 81.8, 83.0, 97.9, 99.7, 113.9, 120.1, 125.2, 125.3, 127.2, 127.8, 129.9, 130.3, 141.4, 142.5, 143.9, 155.9, 159.4, 168.4, 171.7, 172.0, 181.3 ppm; HR FAB MS [M+Na]+ calcd for C69H105NO14Na 1194.7433. found 1194.7433.
