Synthesis of Truncated Carbocyclic Nucleosides Using 5′‐Deoxy‐5′‐Heteroarylsulfonylnucleosides

Abstract

This article describes the detailed protocol for the synthesis of "truncated" carbocyclic nucleosides with a cyclopentene core and without a 4'-hydroxymethyl group. The synthesis was performed using 5'-deoxy-5'-heteroarylsulfonylnucleosides, which were prepared by the 5'-O-mesylation of the appropriately protected nucleosides, followed by a nucleophilic substitution with heteroarylthiols and the oxidation of the resulting 5'-S-heteroaryl-5'-thionucleosides. The treatment of the 5'-deoxy-5'-heteroarylsulfonylnucleosides with 1,8-diazabicyclo[5.4.0]undec-7-ene affords the truncated carbocyclic nucleosides, presumably via a domino reaction involving the α-deprotonation of the heteroarylsulfone, elimination of the nucleobase, formation of an α,β-unsaturated sulfone, Michael addition of the nucleobase to the α,β-unsaturated sulfone, and an intramolecular Julia-Kocienski reaction. This protocol would be useful for the short-step synthesis of biologically active carbocyclic nucleosides. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 5'-deoxy-5'-heteroarylsulfonylnucleosides Basic Protocol 2: Synthesis of truncated carbocyclic nucleosides.