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....

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Veröffentlicht in:	Journal of organic chemistry 2022-11, Vol.87 (22), p.15166-15177
Hauptverfasser:	Jurado, Sergio, Illa, Ona, Álvarez-Larena, Angel, Pannecouque, Christophe, Busqué, Félix, Alibés, Ramon
Format:	Artikel
Sprache:	eng
Schlagworte:	Antiviral Agents - pharmacology Heptanes Nucleosides - pharmacology Stereoisomerism Triazoles
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container_end_page	15177
container_issue	22
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container_title	Journal of organic chemistry
container_volume	87
creator	Jurado, Sergio Illa, Ona Álvarez-Larena, Angel Pannecouque, Christophe Busqué, Félix Alibés, Ramon
description	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.
doi_str_mv	10.1021/acs.joc.2c01661
format	Article
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subjects	Antiviral Agents - pharmacology Heptanes Nucleosides - pharmacology Stereoisomerism Triazoles
title	Conformationally Locked Carbocyclic Nucleosides Built on a 4′-Hydroxymethyl-3′-hydroxybicyclo[4.1.0]heptane Template. Stereoselective Synthesis and Antiviral Activity
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