Figure 1

Chemical stucture of Chenodeoxycholyl–arginine-ethyl ester CDCArg and diagram of synthesis. The synthetic pathway: Chenodeoxycholic acid (78.5 gm, 0.2 mol) was dissolved in DMF (250 mL) and tributylamine (95.3 mL) in 1000 ml round bottom flask. Ethyl chloroformate (20.16 mL) was slowly added to the mixture at 0°C. The mixture was stirred at 0°C for 30 min. In 500 ml round bottom flask, a mixture of arginine ethyl ester dihydrochloride (60.28 gm, 0.22 mol) and tributylamine (95.3 mL) in DMF (200 mL) was prepared. It was transferred to a dropping funnel and slowly added to the mixture of mixed anhydride prepared from chenodeoxycholic acid and ethyl chloroformate at 0°C (step 1). The mixture was stirred at room temperature overnight. The mixture was poured on ice and the gummy residue separated out was collected by separating from water (77 gm). The water from step 5 was concentrated in a rotary evaporator. The residue obtained after concentration was loaded above a silica bed (300 gm) and eluted with methylene chloride followed by methanol –methylene chloride (1:4). The earlier fractions with 100% methylene chloride were discarded since they mostly contained impurities and solvents (i.e. DMF and tri-buylamine). The later fractions were concentrated and provided a gummy residue (45 gm). The crude product from step 7 (77 gm) and step 11 (45 gm) was dissolved in methanol and combined. It was then purified on the Teledyne Isco 330 gm silica gel column using 10-15% methanol –methylene chloride. The purification was carried out on Combi-Flash using the ELSD detector. Three separate runs were performed. The pure fraction were collected and concentrated on rotary evaporator to give compound 1 (50.8 gm). Reaction was repeated following the above procedure.