Graduation Term
Summer 2025
Degree Name
Master of Science (MS)
Department
Department of Chemistry
Committee Chair
Shawn Raynard Hitchcock
Committee Member
Andy Mitchell
Committee Member
Jon Friesen
Abstract
1,2,4-Oxadiazoles are five-membered heterocyclic structures first synthesized by Tiemann and Krüger in 1884. Recent discoveries suggest an array of useful biological properties.In preparation of 1,2,4-oxadiazoles, the most prevalent precursors are amidoximes, which can be created via the reaction of nitriles with hydroxylamine hydrochloride and a base. The amidoximes are reacted with an activated carboxylic acid to yield an acylated intermediate. This intermediate can be exposed to a base to cyclize into the 1,2,4-oxadiazole. This thesis describes the efforts in combining these three steps into a unified one-pot synthesis.
Currently, there are a significant number of commercially available FDA approved and investigational 1,2,4-oxadiazole medicinal agents, such as ataluren for Duchenne muscular dystrophy. Duchenne muscular dystrophy is a genetic disease that involves the weakening of muscle fibers due to a deficiency in dystrophin. Ataluren increases the production of dystrophin through a readthrough mechanism it employs on the ribosome. Subsequently, this work describes the utilization of the one-pot 1,2,4-oxadiazole studies to target the drug ataluren.
The worldwide pandemic started by the spreading of the novel coronavirus (SARS-CoV-2) that originated in central Asia. Although vaccines were developed to fight the disease, societal factors influenced the pursuit of small molecule therapeutic agents. Rathi and co-workers carried out computational studies on the replication event of the COVID-19 virus through exploitation of the 3CLpro protease, acquiring a structure of a high potential protease inhibitor. Finally, this work describes the synthetic pathway to the proposed molecule utilizing an asymmetric aldol addition mediated reaction to set the foundation.
Access Type
Thesis-Open Access
Recommended Citation
Carter, Austin J., "The Development of a One Pot, Two Reaction Synthetic Preparation of 1,2,4-Oxadiazole, and Synthesis of Ataluren, a Novel Drug in the Fight Against Duchenne Muscular Dystrophy. Efforts Towards the Synthesis of a Potential Protease Inhibitor Against the Main Protease (3Clpro) of COVID-19" (2025). Theses and Dissertations. 2155.
https://ir.library.illinoisstate.edu/etd/2155
DOI
https://doi.org/10.30707/ETD.1763755359.00815