Conformationally Locked Carbocyclic Nucleosides Built on a 4′-Hydroxymethyl-3′-hydroxybicyclo[4.1.0]heptane Template. Stereoselective Synthesis and Antiviral Activity

Two new families of enantiomerically pure carbocyclic nucleoside analogues based on a cyclohexane moiety with five chiral centers and a fused cyclopropyl ring have been synthesized. A highly regio- and stereoselective synthetic approach for the modular construction of the functionalized bicyclo[4.1....

Full description

Saved in:
Bibliographic Details
Published in:Journal of organic chemistry 2022-11, Vol.87 (22), p.15166-15177
Main Authors: Jurado, Sergio, Illa, Ona, Álvarez-Larena, Angel, Pannecouque, Christophe, Busqué, Félix, Alibés, Ramon
Format: Article
Language:English
Subjects:
Antiviral Agents - pharmacology
Heptanes
Nucleosides - pharmacology
Stereoisomerism
Triazoles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Two new families of enantiomerically pure carbocyclic nucleoside analogues based on a cyclohexane moiety with five chiral centers and a fused cyclopropyl ring have been synthesized. A highly regio- and stereoselective synthetic approach for the modular construction of the functionalized bicyclo[4.1.0]­heptyl azide intermediate 6 has been established. Key steps to achieve this asymmetric synthesis involved highly diastereoselective allylic oxidation and hydroboration reactions. The first family of compounds, 1a,b and 2, presents different natural nucleobases, whereas the second one 3a–e bears functionalized 1,2,3-triazoles. These derivatives have been tested as antiviral agents, and compound 3d has shown to display moderate activity against coxsackie B4 virus.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.2c01661