Regioselective synthesis of 5′-amino acid esters of some nucleosides via orthogonal protecting protocol

Amino acid esters of nucleosides at 5′-position, as peptidomimetic prodrugs, which could be actively transported by the intestinal oligopeptide transporters 1 (PepT1), bear improved oral bioavailability. We established here a regioselective synthesis of the 5′-esters of some nucleosides via an orthogonal protecting protocol with triphenylmethyl (Tr) and allyloxycarbonyl (AOC) protecting groups. A series of 5′-esters of cytarabine and gemcitabine were selectively synthesized in over 36.0% total yields. This efficient and robust methodology will be examplified for the further study of the prodrugs of large number of antiviral and anticancer nucleosides.

Graphical abstractDownload full-size image