Synthesis of Cyclo and Backbone Extended Nucleosides

Abstract

Nucleic acids are essential biological molecules that encode and transfer genetic information from generation to generation. Intensive efforts have been made by scientists to study the properties of nucleic acids, looking for opportunities that could help diagnose, prevent, and cure disease, and/or gain a greater insight into the wonder of nature. Chapter 2 presents our synthetic attempts towards the rigidified nucleosides 2'-deoxy-6,3'-propanouridine and 2'-deoxy-6,3'-butanouridine. These nucleosides are constrained so that they mimic the native conformation in DNA duplex and are postulated to increase duplex stability, as well as increase the affinity of the nucleobase for its complementary partner. Chapter 3 presents work towards the synthesis of backbone extended nucleosides. These molecules have the potential to form a new type of helical structure when incorporated into a double helix. Through the investigation of these novel nucleic acids, we would like to gain a greater understanding of the properties that contribute to duplex stability.