Reaction Steps
To a stirred solution of the compound (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan methyl ester (170 mg, 0.3222 mmol, 1.0 eq.) in a mixture THF-MeOH (ratio 3:2) (10 mL) was added 0.5N LiOH (5.0 mL). The resulting yellowish mixture was stirred at room temperature for 30 min during which TLC shows the complete disappearance of the starting material. The reaction mixture was then neutralized with glacial acetic acid and the extracted with EtOAc (3×25 mL), dried over anhydrous MgSO4 and evaporation of the solvent gave a crude residue, which was subjected to column chromatography on silica gel elution with 30% MeOH-EtOAc afforded the free acid (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan 5b as a pale yellow solid (0.158 g, 95%); mp 171-173° C.; Rf 0.38 (30% MeOH-EtOAc); IR (KBr) ν 1720 (CO), 3250 (broad, COOH) cm−1; 1H NMR (400 MHz, CDCl3) δH 2.31 (2H, m, —CH2CO), 2.70 (2H, m, —CH2CO), 2.96 (1H, m, —CHαPh), 3.24 (3H, m, —CHβPh and —CH2Trp),), 4.84 (1H, m, —CH—), 4.90 (1H, m, —CH—), 6.49 (1H, t, J=7.2 Hz, —NH), 6.92-7.66 (16H, m, Ar—H and —NH) and 8.48 (1H, d, J=6.0 Hz, —NH); 13C NMR (100 MHz, CDCl3) δC 27.2, 29.5, 35.0, 35.1, 36.5, 53.2, 59.5, 59.6, 109.5, 111.4, 118.5, 119.6, 122.0, 123.5, 127.0, 127.1 (2C), 127.4, 128.6, 128.7 (2C), 129.2, 132.0, 133.5, 136.1, 167.7, 172.4, 174.6 and 207.8; HRMS m/z calcd for C30H29N3O5 (M+) 511.21072, found 511.21072. [± The carboxylic acid and amide protons were not observed, presumably, due to rapid exchange with water in the deuteriated NMR solvent.]
