Spirocyclic Restriction of Nucleosides

Abstract

The concept of spirocyclic restriction as applied broadly to the field of nucleoside mimics makes possible the generation of diastereomeric pairs configured with a syn- or anti-oriented hydroxyl substituent at C5′. The development of concise synthetic routes to spiro-fused nucleosides bearing all possible natural bases and expectedly capable of enforcing a conformation favourable for duplex formation on incorporation into oligomers represents a significant new direction in the design of antisense molecules. The present overview describes the convenient approaches that have been developed in this laboratory for accessing varied members of this class, including analogues that feature sulfur and carbon at the apical position.