Date of Award

2021

Document Type

Thesis

Degree Name

MS in Chemistry

Department

Chemistry

First Advisor

Sabesan Yoganathan

Second Advisor

Alison G Hyslop

Third Advisor

David P Brown

Abstract

α-Mangostin belongs to a class of polyphenolic compounds called xanthones. The potential pharmacological effects such as anti-bacterial and anti-cancer effects of α-mangostin have made it an important natural product for medicinal chemistry evaluation. During this thesis research, we have designed and synthesized a series of non-xanthone analogs of α-mangostin for medicinal chemistry evaluation. A commercially available starting material, methyl-4-methoxysalicylate was used to synthesize these non-xanthone analogs. The analogs were designed as more flexible derivatives compared to the tricyclic motif within α-mangostin yet retain the hydroxybenzoate scaffold. Through a one-pot chemical synthesis, with relatively high yield (70%), we prepared eight different benzyl-ether analogs. The benzyl-ether scaffolds contained various substituents at the 4-positon of the aryl ring, and we evaluated the effect of these substituents on the antibacterial activity. Moreover, the alkylation chemistry we have utilized is very simple to do and suitable for the large-scale preparation of these analogs. The chemical approach reported here can be extended to incorporate various benzyl and alkyl motifs at the 2-position of the methyl-4-methoxysalicylate core for elaborate medicinal chemistry efforts. Our initial antibacterial activity evaluation of selected derivatives from this series showed no activity at 100 µM concentration against S. aureus and S. epidermidis strains. Our future plan is to evaluate the antibacterial activity of these analogs against a larger panel of bacteria.

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