Synthesis and characterization of caffeic acid and dihydrocaffeic acid derivatives as antifungal agents

Chen, Yuxi (2016) Synthesis and characterization of caffeic acid and dihydrocaffeic acid derivatives as antifungal agents. Masters thesis, Memorial University of Newfoundland.

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Abstract

Invasive fungal infection, a major cause of morbidity and mortality in immuno-compromised hosts, is of importance and is significantly increasing in incidence in recent years. Although there are a number of antifungal agents currently available, they are associated with various limitations. Being inhibitors of fungal cell wall biosynthesis, the class of echinocandins is characterized by outstanding safety profiles and great potential in combination antifungal therapy, but they fall short in oral bioavailability. A discovery of peptidomimetic analogues of echinocandin B, with potential inhibitory activity against 1,3-β-D-glucan synthase (an enzyme essential for the biosynthesis of fungal cell walls), was initiated by our research group. A series of structurally related derivatives (chlorogenic, quinic, caffeic and dihydrocaffeic acid derivatives) were later designed to mimic the backbone of echinocandins. Further studies have been carried out on optimization of synthesis and modifications of a caffeic acid derivative. Due to the instability problems of previously reported compounds, a new molecule, a dihydrocaffeic acid derivative, has been designed and synthesized. It was found that adopting a few optimized procedures can not only improve the yield and purity of the caffeic acid derivatives, but also save a lot of time in synthesis.

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