Structural Diversity of Perylenequinones Is Driven by Their Redox Behavior

[Image: see text] Hypocrellins and hypomycins are two subclasses of fungal perylenequinones with unique structural, biological, and photochemical properties. With the growing interest in these naturally occurring photosensitizers, more studies were warranted to better understand the structural relationships between these two subclasses of perylenequinones. In this study, the long-postulated biosynthetic precursor (7) of class B fungal perylenequinones was isolated and characterized from a Shiraia-like sp. (strain MSX60519). Furthermore, the electrochemical and chemical redox behaviors of hypocrellins and hypomycins were investigated under aerobic and anaerobic conditions. These studies served to define the structural relationship within hypocrellins (1–3), which was further supported by X-ray crystallography, and between hypocrellins and hypomycins (4–6). Chemical reductions of hypocrellins under anaerobic conditions identified the origin of hypomycin A (4), hypomycin C (5), and hypomycin E (6), which in turn served to confirm 4 and revise the absolute configurations of 5 and 6. Hypocrellins were shown to undergo reversible reduction and reoxidation under aerobic conditions, while in an anaerobic environment and longer time scale, the fully reduced form can, to some extent, undergo an intramolecular ring closing metathesis. This may impart a means of reductive pathway for self-protection against these phototoxins and explain the chemical diversity observed in the fungal metabolites.