To a round bottom flask was added (S)-4-(acetylthio)-2-(benzyloxycarbonylamino)butanoic acid (312 mg, 1.00 mmol), 5-aminopentan-1-ol (119 mg, 1.15 mmol), DCM (5 mL), EDC (211 mg, 1.10 mmol) and HOBt (184 mg, 1.20 mmol). The light yellow mixture was stirred at rt for 16 hr. The reaction mixture was diluted with EtOAc (60 mL), washed with 5% aqueous KHSO4 (2×), saturated aqueous NaHCO3 (2×), water, and saturated aqueous NaCl. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give (S)—S-3-(benzyloxycarbonylamino)-4-(5-hydroxypentylamino)-4-oxobutyl ethanethioate (311 mg, 0.784 mmol, 78% yield) as a white solid. Anal. Calcd. for C19H28N2O5S m/z 396.5. found: 397.3 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.47-7.28 (m, 5H), 6.41 (s, 1H), 5.59 (d, J=6.7 Hz, 1H), 5.11 (s, 2H), 4.13 (d, J=6.7 Hz, 1H), 3.63 (dd, J=11.6, 6.1 Hz, 2H), 3.28 (dd, J=12.7, 6.3 Hz, 2H), 2.97 (dt, J=14.5, 7.4 Hz, 1H), 2.91-2.75 (m, 1H), 2.34 (s, 3H), 2.21-2.00 (m, 1H), 1.91 (dt, J=14.4, 7.2 Hz, 1H), 1.72-1.48 (m, 5H), 1.48-1.34 (m, 2H).
