Synthesis of new acetylsalicyclic acid derivatives via amino acids and amino alcohols

Dönmez, B. Synthesis of New Acetylsalicyclic Acid Derivatives Via Amino Acids and Amıno Alcohols, Hacettepe University Health Sciences Institute M.Sci. Thesis in Basic Pharmaceutical Sciences, Ankara, 2018. In this study, total 11 compounds namely 2-(alkylcarbomyl)phenylacetate (9-11, 16, 17) and 2-hydroxy-N-alkylbenz-amide (12-15, 18, 19) were synthesized. Chemical structure of one of these compounds (13) was defined previously in literature. Aminoacids were reacted with thionyl chloride in methanol to give aminoacid ester compounds (1-7). Acetylsalicyl chloride (8) was produced by activation of acetylsalicylic acid (ASA) with thionyl chloride. Acetylsalicyl chloride (8) was then reacted with aminoacid ester compounds (1-7) in the presence of triethylamine via addition and elimination mechanism to form amide derivatives of ASA (9 - 16). (S)-(+)-2-amino-1-propanol, (R)-2-amino-3-phenyl-1-propanol and (2R,3R)-2-amino-3-methylbutane that are homochiral β-amino alcohols were each reacted with acetylsalicyl chloride (8) in presence of triethylamine and DMAP to give other amide derivatives of ASA (17-19 respectively). Physical properties of the synthesized compounds were determined and their chemical structures were elucidated by IR, 1H-NMR, 13C-NMR and mass spectroscopy. Optical rotation values of the optically active compounds were measured by polarimeter and absolute rotation values were calculated. These compounds were designed as amide derivatives of ASA to have low gastric side effect and their activity properties were investigated. Analgesic antiinflammatory effects of the synthesized compounds were carried out via COX enzyme inhibitory experiments by monitoring oxygen uptake with respect to initial ratio using oxygen electrode.