The early discoveries by Mietzsch, Klarer, and Domagk showed that azo dyes which were derived from sulfanilamides had important antistreptococcal activity.^{1,2, 3} Further work by Trefauels, Nitti and Bovet showed that the sulfanilamide moiety was responsible for pharmacological activity of these chemotherapy agents.⁴ Research has shown that indoline and indole sulfonamides have similar mechanisms of action.^5,6 These discoveries have stimulated widespread research on sulfanilamide, sulfonamide and sulfone derivatives by many pharmaceutical, medical, and academic institutions to try and treat a variety of diseases.^7,8,9,10 More recently, sulfonamides and sulfones have been found to act as non-nuclease reverse transcriptase inhibitors in the treatment of HIV-1.¹¹ This research aimed to synthesize new indoline sulfonamide and indoline sulfone libraries with the intention to help combat HIV-1 mutations.

Previous research by Dr. Murray Zanger (Emeritus, USP) has shown that tetrahydroquinoline sulfones and sulfonamides possess some anti HIV-1 activity. ¹¹ The tetrahydroquinoline sulfonamide rearrangement utilizes concentrated sulfuric acid to form a sulfone from a sulfonamide.¹² Unlike tetrahydroquinoline, indoline sulfonamides do not rearrange to the sulfones using concentrated sulfuric acid.¹² This thesis describes attempts toward synthesizing indoline sulfones and rearranging them to their respective sulfones using polyphosphoric acid (PPA). Future studies may focus on studying the pharmacological activity and the possibility of converting the indoline sulfones to indole sulfones.