Reaction Steps
To a solution of Fmoc-Cys(Acm)-OH (855 mg, 2 mmol) in 4 ml dry DCM at 0° C., HOBt (270 mg, 2 mmol) was added. Then an ice-cold solution of H-Phg-OtBu (415 mg, 2 mmol) in 4 ml of dry DCM was added. Subsequently, DIC (319 μl, 2 mmol) was introduced dropwise. After 1 h at 0° C. and 4 h at 4° C., the solution was evaporated under vacuum. The residue was dissolved in 50 ml EtOAc and washed with sat. aq. NaHCO3, 0.5 M HCl and water. After drying and evaporation of the organic phase, the residue was chromatographed on silica gel to give the protected dipeptide 1 as a foam. Yield 1.14 g (95%), Rf 0.35 (DCM/MeOH, 95:5). 1H NMR (CDCL3): δ1.45 (9H, s, tBu), 1.92 (3H, s, CH3 Acm), 2.71-3.1 (2H, m, CβH2 Cys), 3.8 (1H, m, CoH Cys) 4.2-4.5 (5H,m, CH2 Acm. CH—CH2 Fmoc), 4.56-4.85 (3H, m, CoH Phg, Fmoc), 5.4 (1H, d, J=7.3 Hz, NH) 6.47 (1H, d, J=8.4 Hz, NH), 7.2-8.05 (14H, Fmoc+Phg aromatic, NH Acm). 13C NMR (CDCl3): δ23.7 (CH2, Acm), 27.7 (3×CH3, tBu), 34.9 (Cβ, Cys), 41.1 (CH2, Acm), 41.9 (CH2, Fmoc), 57.4 (CαPhg), 83.7 (Cq tBu), 119.7-127.5 (aromatic, Fmoc, Phg), 141.0 and 143.6 (4C, Fmoc), 156.6 (CO, Fmoc), 170.2 (CO, Cys), 173.5 (2×CO, Acm, tBu ester).
