New synthesis of (+/-)-isonucleosides

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Virology

Background:

• Isonucleosides represent a novel class of nucleoside analogs with potential antiviral activity.
• Developing efficient synthetic routes is crucial for exploring their therapeutic potential, particularly against viruses like HIV.

Purpose of the Study:

• To describe a novel synthetic methodology for producing isonucleoside derivatives.
• To establish a pathway for generating 4'-substituted 2',3'-dideoxyisonucleosides.

Main Methods:

• A six-step synthesis starting from 2,2-Dimethyl-1,3-dioxan-5-one to form a dioxabicyclohexane derivative.
• Epoxide cleavage using thiophenol, followed by a Mitsunobu reaction with a nucleobase to yield the isonucleoside core.
• Radical deprotection and thiophenyl group removal to afford the final 4'-substituted 2',3'-dideoxyisonucleosides.

Main Results:

• Successful synthesis of a novel isonucleoside derivative through a multi-step process.
• Demonstration of the thiophenyl group's migration during the Mitsunobu reaction.
• Obtention of the target 4'-substituted 2',3'-dideoxyisonucleosides as a racemic mixture.

Conclusions:

• A new, viable synthetic route for isonucleosides has been established.
• The described method offers a pathway for the synthesis of potential anti-HIV agents.
• Further research can explore the antiviral efficacy and stereoselective synthesis of these compounds.