Medicinal chemistry is a fast-evolving discipline. Since the early 2000s is shifting its interest from a traditional small molecule's “flat” domain to a 3D molecular space that can address the ongoing demand for therapeutic solution targeting unmet clinical diseases. In this context, during the last years new classes of compounds are being used as therapeutic agents; among them, DNA- and RNA-based therapeutics agents are gaining a prominent role in drug process development. Natural nucleosides, the fundamental building blocks of these therapeutic agents, are numerically limited and show poor biological stability properties. To overcome these limitations and to have access to a DNA/RNA based drug with an improved profile, the synthesis of nucleosides analogues is a cornerstone strategy pursued by medicinal chemistry. Although several sites of modifications of the natural occurring nucleosides can be identified, the most widespread decorations involve the ribose moiety in C1, C2 and C3. Moreover, the reported methodologies often require many synthetic steps and make these approaches poorly sustainable. The aim of the eGreenchem project is to allow the access to an unprecedent class of nucleosides analogues by C-H functionalization of the C-5 position of the ribose moiety. We plan to perform such transformation via the electrochemical-mediated radical generation of a C5 carbon centered radical and its subsequent reaction with various radical acceptors. Organic electrochemistry can facilitate the selective formation of the radical, instead of others regioisomers, and thus the specific functionalization of complex scaffolds. This transformation would represent a state-of-the-art advancement in the decoration of sp3-based scaffold, another popular trend in medicinal chemistry. The outcome of this project will further result in the synthesis of a nucleosides analogues library targeting a new molecular space for the development of novel drug candidates.