Masters Thesis

Synthesis of stabilized sulfenic acids

Aging and age-related diseases, such as cancer, Alzheimer’s, and cardiovascular diseases, are incredibly complex and result from multifactorial processes. However, a common hallmark in development of these diseases is the failure of the body’s antioxidant defense system, which results in accumulative oxidative damage. Antioxidant supplementation has been reported to significantly reduce the damaging effects of oxidative stress and also decrease the risk of associated diseases. Sulfenic acids (RSOH), the sulfur analogue of hydroperoxides, have recently been suggested to be among the most potent of antioxidants and can efficiently terminate radical chain oxidation reactions. Despite their promise, the potential of sulfenic acids has yet to be harnessed as most sulfenic acids are far too unstable to be isolated. Much of our current knowledge has been obtained in very indirect and speculative manners, and the correlation between structure and stability of sulfenic acids remains fragmented. To bridge this gap in knowledge, we aim to identify and synthesize a new model scaffold for stable sulfenic acids. By finding a model scaffold and systematically introducing substituents that can stabilize the sulfenic acid through intramolecular hydrogen bonding, steric hindrance, or inductive effects, we can directly study how structure relates to stability. Herein, we present the syntheses and the structural modifications of several sulfoxide scaffolds derived from ethylphenyl acetate, quinoline, lumazine, and caffeine. Structural elucidation of the sulfoxides was carried out through FT-IR, 1H NMR, 13C NMR, and MS. Subsequently, the synthesized sulfoxide derivatives were subjected to S-type Cope elimination to afford the free sulfenic acid and the stability of the sulfenic acids were evaluated.