Reaction Steps
The experimental procedure employed for the synthesis of (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-proline benzyl ester was followed using the free acid compound 9 (98 mg, 0.3054 mmol, 1.0 eq.), L-tryptophan methyl ester (67 mg, 0.3054 mmol, 1.0 eq.), 1-Hydroxybenzotriazole hydrate (HOBt) (42 mg, 0.3054 mmol, 1.0 eq.), N-ethyl-IV-(dimethylaminopropyl)-carbodiimide hydrochloride (EDC.HCl) (59 mg, 0.3054 mmol, 1.0 eq.), iPr2NEt (0.055 mL, 0.3054 mmol, 1.0 eq.) and dry DMF/CH2Cl2 (2:8 ratio)(5 mL). Work-up as usual and column chromatography on silica gel elution with 50% EtOAc-hexane afforded the (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-tryptophan methyl ester (NACE 118) as a cream white solid (0.129 g, 81%): mp 54-57° C.; Rf 0.34 (50% EtOAc-hexane); IR (KBr) ν 1680 (CO) and 3000 (broad, NH) cm−1; 1H NMR (400 MHz, CDCl3) δH 1.40 (9H, s, (CH3)3), 2.41 (2H, t, J=6.6 Hz, —CH2CO), 2.74 (2H, m, —CH2CO), 2.88 (1H, m, —CHαPh), 3.10 (1H, m, —CHβPh), 3.30 (2H, m, —CH2Trp), 3.68 (3H, s, OCH3), 4.47 (1H, br s, —NH), 4.89 (1H, dd, J=5.5 and 11.0 Hz, —CH—), 5.03 (1H, m, —CH—), 6.07 (1H, d, J=7.3 Hz, —NH), 7.08-7.58 (10H, m, Ar—H) and 8.15 (1H, br s, —NH-indole); 13C NMR (100 MHz, CDCl3) δC 27.5, 28.3, 30.8, 35.4, 37.5, 52.3, 52.9, 53.0, 60.1, 111.2, 118.5, 119.7, 122.2, 122.9, 123.0, 126.9, 127.7, 128.6, 129.2, 129.3, 136.1, 136.3, 136.4, 155.4, 172.2, 172.3 and 204.6; EI-MS m/z calcd for C29H35N3O6 (M+) 521.2526, found 521 (M+).
