Synthesis and Characterisation of Novel Amino Acid-Antioxidant Conjugates

Novel low molecular weight amino acid-functionalised antioxidant molecules containing a sterically hindered phenolic group have been synthesised. Precursor building block syntheses involved Miyaura borylation and Williamson ether coupling, while the synthesis of target molecules involved a Suzuki reaction and amide coupling, where all above processes had yields of ca. 40% - ca. 80% (Scheme 1). This methodology can be applied to functionalise amino esters with antioxidant groups, of which the ester group can then be deprotected afterwards. The methodology provides a viable pathway in case multiple amino acid units are required to be appended to the main structure. Evidence of self-assembly was evaluated using the 1H NMR dilution titration experiment, where the data were used to calculate the association constants (10-100 M-1) for the amino acid-antioxidant conjugates with respect to water. Antioxidant activity of target antioxidant molecules was measured by utilising 2,2-diphenyl-1-picrylhydrazyl (DPPH˙) radical scavenging assay using UV-vis spectroscopy. All the molecules act as antioxidants (Scheme 2) with radical scavenging activities of above 35% from novel amino methyl ester conjugates and above 60% from novel amino acid conjugates.