Synthesis of certain 4'-substituted nucleosides

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Nucleoside Chemistry

Background:

• Nucleosides are fundamental building blocks in nucleic acids and play vital roles in biological processes.
• Modified nucleosides are essential for developing antiviral and anticancer therapeutics.
• Current synthetic methods for nucleoside modification present challenges in regioselectivity and yield.

Purpose of the Study:

• To develop general and efficient synthetic methodologies for 4 -fluoro- and 4 -methoxynucleosides.
• To synthesize analogs of the antibiotic nucleocidin with potential therapeutic applications.

Main Methods:

• Addition of iodine monofluoride or iodine and methanol across the double bond of protected 4 ,5 -unsaturated pyrimidine and purine nucleosides.
• Structure elucidation using a combination of chemical, spectroscopic (NMR, Mass Spectrometry), and electrophoretic techniques.

Main Results:

• Successful synthesis of 4 -fluoro- and 4 -methoxynucleosides using the developed methods.
• Characterization of the synthesized adducts, confirming their structures.
• Synthesis of 4 -methoxy- and uridine analogs of nucleocidin from 4 -fluorouridine and 4 -methoxyadenosine derivatives, respectively.

Conclusions:

• The developed methods provide a versatile approach for synthesizing valuable 4 -fluoro- and 4 -methoxynucleoside derivatives.
• These findings contribute to the advancement of nucleoside chemistry and the development of novel therapeutic agents.