Reaction Steps
The experimental procedure employed for the synthesis of (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-proline benzyl ester was followed using the free acid compound 4 (200 mg, 0.6109 mmol, 1.0 eq.), L-tryptophan methyl ester (133 mg, 0.6109 mmol, 1.0 eq.), 1-Hydroxybenzotriazole hydrate (HOBt) (83 mg, 0.6109 mmol, 1.0 eq.), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (EDC.HCl) (117 mg, 0.6109 mmol, 1.0 eq.), iPr2NEt (0.11 mL, 0.6110 mmol, 1.0 eq.) and dry DMF/CH2Cl2 (2:8 ratio)(10 mL). Work-up as usual and column chromatography on silica gel elution with 100% EtOAc afforded the (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan methyl ester as a yellow solid (0.290 g, 90%); mp 88-90° C.; Rf 0.50 (EtOAc); IR (KBr) ν 1760 (CO), 3230 (NH) cm−1; 1H NMR (300 MHz, CDCl3) δH 2.44 (2H, m, —CH2CO), 2.82 (2H, m, —CH2CO), 3.06 (1H, m, —CHαPh), 3.28 (3H, m, —CHβPh and —CH2Trp), 3.67 (3H, s, —OMe), 4.90 (1H, m, —CH—), 4.99 (1H, m, —CH—), 6.17 (1H, dd, J=2.7 and 7.5 Hz, —NH), 6.88 (1H, d, J=6.9 Hz, —NH), 7.00 (1H, dd, J=2.8 and 6.4 Hz, Trp-H-5′), 7.02-7.56 (12H, m, Ar—H), 7.68 (1H, d, J=1.8 Hz, Trp-H-2′), 7.71 (1H, d, J=1.8 Hz, Ar—H) and 8.27 (1H, br-s, —NH); 13C NMR (75 MHz, CDCl3) δC 27.6, 29.7, 35.0, 35.1, 36.8, 36.9, 52.3, 53.0, 59.4, 59.6, 109.9, 111.3, 118.5, 119.7, 122.2, 123.0, 127.0, 127.6 (2C), 128.5, 128.6 (2C), 129.3, 131.8, 133.8, 136.1, 136.2, 167.1, 171.1, 172.3 and 207.5; HRMS m/z calcd for C31H31N3O5 (M+) 525.22637, found 525.22637.
