PEGYLATED TACROLIMUS DERIVATIVES AND PROCESS FOR PREPARING THE SAME

摘要

A process for preparing pegylated tacrolimus derivatives having improved water solubility and bioavailability is provided to improve simplicity, economical efficiency and yield of pegylation by linking PEG(poly(ethylene glycol)) to tacrolimus derivatives and inhibiting side reactions. A process for preparing pegylated tacrolimus derivatives comprises the steps of: dissolving polyethylene glycol monomethyl ether(MeO-PEG) represented by the formula(5) in organic solvent, and halocarbonylating with phosgene in the presence of base at -5 to 5 deg. C to prepare compounds represented by the formula(6); and dissolving the compounds represented by the formula(6) and tacrolimus in organic solvent and reacting with base at -5 to 5 deg. C, wherein n is an integer from 38 to 46. Further, the phosgene is tri-phosgene.