Preparation of Novel 4’-Spirocyclopropyl Nucleoside Analogues

The stereoselective preparation of a novel 4’-spirocyclopropyl nucleoside analogue has been described using a semi-benzilic Favorskii rearrangement of a 4’-(2-chloro-3-oxocyclobutyl)spirofuranose as a key step. We demonstrated that the latter chiral spirocyclic intermediates, readily obtained on multigram scale from chiral pool starting materials, are highly suitable precursors to obtain full stereoselectivity in the reduction-ring contraction sequence. The downstream nucleobase introduction via Vorbruggen glycosylation successfully resulted in the formation of the corresponding novel 4’-spirocyclic nucleoside analogue in a stereospecific manner.