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Structural Diversity of Perylenequinones is Driven by their Redox Behavior

Lookup NU author(s): Dr Kin Lok Ho, Dr Michael HallORCiD, Dr Mike ProbertORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

Hypocrellins and hypomycins are two sub-classes of fungal perylenequinones with unique phototoxic properties. Of these, more is known about hypocrellins, which were reported to have phototoxic activity against a variety of cancer cell lines and microbes; only limited pharmacological studies have been reported on hypomycins, in which the characteristic conjugated system of the perylenequinones has been partially disrupted. With the growing interest in these compounds as naturally-occurring photosensitizers, more studies were warranted to better understand the structural relationships between these two sub-classes 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, suggesting the ability of hypocrellin-producing fungi to defend themselves against their own toxins by reducing these photosensitizers anaerobically. These studies also served to define the structural relationship within hypocrellins (1-3), 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. These structural findings were further supported by X-ray crystallographic data. Hypocrellins were shown to possess two fully reversible reduction processes, electrochemical and chemical, under aerobic conditions. However, in an anerobic environment and longer timescale, the fully reduced form can, to some extent, undergo an intramolecular ring closing metathesis, and this may impart a means of self-protection from the toxicity of these molecules and explain the chemical diversity observed in the fungal metabolites.


Publication metadata

Author(s): AlSubeh ZY, Waldbusser A, Raja HA, Pearce CJ, Ho KL, Hall MJ, Probert MR, Oberlies NH, Hematian S

Publication type: Article

Publication status: Published

Journal: Journal of Organic Chemistry

Year: 2022

Volume: 87

Issue: 5

Pages: 2697-2710

Print publication date: 04/03/2022

Online publication date: 25/01/2022

Acceptance date: 25/01/2022

Date deposited: 09/02/2022

ISSN (print): 0022-3263

ISSN (electronic): 1520-6904

Publisher: American Chemical Society

URL: https://doi.org/10.1021/acs.joc.1c02639

DOI: 10.1021/acs.joc.1c02639


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Funding

Funder referenceFunder name
EP/F03637X/1EPSRC
P01 CA125066
MR/T000740/1Medical Research Council (MRC)

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