Chemical synthesis and biological evaluation of 4′-thionucleosides

Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers and viruses. Several such compounds, including Sofosbuvir and Gemcitabine are the go-to option in first line treatments. However, these compoundss do have limitations (poor cellular uptake, low conversion to the active triphosphate metabolite, rapid degradation or clearance and development of resistance profiles in certain cell types) and the development of next generation compounds remains a topic of significant interest and necessity. This project broadly involves the chemical synthesis of thionucleoside analogues, a class of molecules which act as antimetabolites and are known to have antiproliferative activity against numerous cancers, viruses and bacteria. The thionucleoside targets herein are inspired by current nucleoside analogue drugs on the market, and they have potential for both greater potency and improved metabolic stability in vivo.