Synthesis of a Threosyl‐C‐nucleoside Phosphonate

Abstract

A general synthetic route for the preparation of the first analogue of a new series of sugar‐modified C‐nucleoside phosphonates is detailed. Such derivative contains a four‐carbon l‐threose sugar moiety substituted with a phosphonomethoxy group at the 3′‐position and pyrrolo[2,1‐f][1,2,4]triazin‐4‐amine as nucleobase. A C‐nucleoside was initially prepared by coupling a benzyl protected l‐threono‐1,4‐lactone intermediate with the corresponding aglycon moiety. The choice of a tert‐butyldiphenylsilyl group was found to be crucial to achieve the regioselective protection of the hydroxyl group at the 3′‐position. Moreover, it allowed to smoothly perform further synthetic manipulations, including the introduction of a benzyl protected phosphonate synthon under basic conditions, which eventually led to the desired compound after final deprotection.