Natural products, derived from plants, microorganisms, and animals, remain central to drug discovery and hold significant agricultural and ethnobotanical relevance. This dissertation, as part of an interdisciplinary effort to study fungal metabolites, focuses on perylenequinones and naphthoquinones, addressing their sustainable production, structural modification, and broader applications. In the first project, a novel methodology was developed for the scalable production of perylenequinones. Stable isotope labeling provided deeper insights into their biosynthesis, revealing connections between redox biology, fungal metabolism, and chemical signaling with direct implications for the stability and therapeutic function of perylenequinone-based photodynamic therapy (PDT) agents under hypoxic, reducing conditions. The second project directed attention toward structural modifications of hypocrellin B and ent-shiraiachrome A, where targeted derivatization generated analogues with enhanced phototherapeutic activity and reduced dark toxicity. The third project explored the chemical diversity of naphthoquinones from Pyrenochaetopsis sp., leading to the discovery of novel heterodimeric and perenniporide-type naphthoquinones, with several showing cytotoxic activity. Finally, the broader significance of perylenequinones and naphthoquinones is considered, extending beyond therapeutics to applications in photocatalysis and redox battery technologies. Overall, this dissertation integrates natural product chemistry, biosynthetic investigation, and applied sciences to advance both the fundamental understanding and practical development of fungal metabolites.
