Rhodium-catalyzed reductive modification of pyrimidine nucleosides, nucleotide phosphates, and sugar nucleotides

Area of Science:

• Biochemistry
• Organic Chemistry
• Medicinal Chemistry

Background:

• Nucleosides and nucleotides are crucial small molecules involved in cellular processes.
• Previous work demonstrated reduced toxicity of hydrogenated tunicamycin, a nucleotide antibiotic.
• The chemical modification of nucleosides and nucleotides is an active area of research for therapeutic applications.

Purpose of the Study:

• To investigate the hydrogenation of various classes of nucleosides and nucleotides.
• To characterize the resulting products and their chemical transformations.
• To explore the potential for generating novel nucleoside and nucleotide derivatives with altered properties.

Main Methods:

• Catalytic hydrogenation of diverse nucleosides and nucleotides.
• Structural elucidation of reaction products using spectroscopic techniques.
• Analysis of reaction pathways, including deamination reactions.

Main Results:

• Quantitative reduction of uridyl and thymidinyl nucleosides to their 5,6-dihydro counterparts.
• Reduction of cytidyl pyrimidines yielding 5,6-dihydrouridyl nucleosides via deamination.
• Successful hydrogenation of diverse sugar nucleosides and nucleotide phosphates.

Conclusions:

• Hydrogenation is an effective method for modifying nucleosides and nucleotides.
• The study provides a detailed understanding of the chemical transformations involved in the reduction of pyrimidine nucleosides.
• The generated 5,6-dihydro nucleosides represent a new class of compounds with potential applications in medicinal chemistry.