Synthesis of Novel Spirocyclohexyl Nitroxide for Use as Organic Radical Contrast Agent (ORCA) in MRI

• Main Author: Ackerman, Elise
• Format: Text
• Language: unknown
• Published: DigitalCommons@University of Nebraska - Lincoln 2022
• Subjects: Chemistry; Organic Radicals; Magnetic Resonance Imaging; Organic Synthesis; Education; Higher Education; Organic Chemistry; Orca
• Online Access: https://digitalcommons.unl.edu/honorsembargoed/259; https://digitalcommons.unl.edu/context/honorsembargoed/article/1261/viewcontent/Ackerman_Elise_Thesis.pdf

An important aspect of medical analysis, Magnetic Resonance Imaging (MRI) commonly utilizes contrast agents to enhance signal resolution. Currently, the vast majority of contrast agents contain the element gadolinium (Gd). Thermodynamic studies indicate that physiological ion replacement results in the release of free Gd3+ from gadolinium-based contrast media, resulting in potentially fatal consequences for patients with kidney disorders. Organic Radical Contrast Agents (ORCAs) present a safe alternative to gadolinium, providing comparable signal resolution while avoiding the toxic effects of heavy metal ions. Recent investigation has shown that ORCAs constructed using spirocyclohexyl nitroxides present promising water solubility, 1H water relaxivity (r1), and resistance to reduction by ascorbate in the bloodstream. Herein we present synthesis of key intermediates leading to a novel spirocyclohexyl nitroxide. The successful synthesis, purification, and characterization of multiple intermediates is demonstrated.