Purpose: This review advances the synthesis methodologies, biological roles, and therapeutic applications of nucleoside derivatives, emphasizing their pivotal role in the development of biomedical sciences. Methodology: There are several methods for synthesizing nucleosides, including fusion reactions, metal salt procedures, and the Hilbert-Johnson method, each of which offers distinct advantages and challenges. These synthetic approaches take advantage of the interaction of sugars and nitrogenous bases, allowing for tailored modifications for specific applications. Findings: Nucleoside derivatives, essential molecules that are the building blocks of nucleic acids such as DNA and RNA, exhibit diverse structural and functional properties. Their biological synthesis, through novel pathways or rescue mechanisms, ensures the availability of the primary genetic material. Synthetic nucleoside derivatives have found significant roles in medicinal chemistry, particularly in antiviral, anticancer and antibacterial therapies. Modifications of sugars or basic components have led to the emergence of pioneering drugs such as acyclovir, zidovudine and remdesivir. Unique Contribution to Theory, Practice and Policy: Nucleoside derivatives have great therapeutic potential. They act as antiviral agents by disrupting viral replication and as chemotherapeutics targeting rapidly dividing cells in cancers. However, their efficacy faces challenges such as toxicity and development of resistance. Ongoing research aims to enhance their safety and expand their applications in molecular biology, diagnostics and nanotechnology.
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