Sodium Bicarbonate → O-(Nalpha-(Nalpha,Nepsilon-Bis(t-butoxycarbonyl)-L-lysinoyl)-Nepsilon-(t-butoxycarbonyl)-L-lysinoyloxy)methyl S-ethyl carbonothioate

Participants

Reaction Steps

To a mixture of dipeptide 51 (969 mg, 1.69 mmol) in H2O (3.25 mL) and CH2Cl2 (3.25 mL) was added NaHCO3 (294 mg, 3.50 mmol) and TBAHSO4 (572 mg, 1.69 mmol). After stirring for 15 min, S-ethyl O-iodomethyl carbonothioate (322 mg, 1.30 mmol) in CH2Cl2 (1 mL) was added. The biphasic reaction was stirred vigorously for 2.5 h and was diluted with water and CH2Cl2. The layers were separated, the organic layer was washed with H2O, 0.5 N HCl solution, saturated NaHCO3 solution, saturated NaCl solution, dried over MgSO4, filtered and concentrated to dryness. The crude product was triturated with Et2O and the solids were removed by filtration and rinsed with small portions of Et2O. After concentration, the combined filtrates were purified by flash chromatography on silica gel, using a gradient of 0-50% EtOAc in CH2Cl2 as eluent to provide compound 52 (818 mg, 91%) as a white foam. 1H NMR (400 MHz, CDCl3) δ 1.30-1.53 (m, 8H), 1.33 (t, J=7.4 Hz, 3H), 1.44 (s, 27H), 1.60-1.75 (m, 2H), 1.82-1.90 (m, 2H), 2.90 (q, J=7.4 Hz, 2H), 3.06-3.14 (m, 4H), 4.04-4.10 (m, 1H), 4.58-4.64 (m, 1H), 4.70 (bs, 2H), 5.18-5.21 (m, 1H), 5.78 (d, J=5.6 Hz, 1H), 5.90 (d, J=5.6 Hz, 1H) 6.67 (bd, J=6.8 Hz, 1H).

Provenance & Evidence