Mechanistic Investigation of the Degradation Pathways of & alpha;-& beta;/& alpha;-& alpha; Bridged Epipolythiodioxopiperazines (ETPs)

Epipolythiodioxopiperazines (ETPs) make up a class ofbiologicallyactive fungal metabolites with a transannular disulfide bridge. Inthis work, we used DFT calculations to examine in detail the degradation(desulfurization) pathways of & alpha;-& beta;/& alpha;-& alpha;bridged ETPs. The chemical stability of ETPs is influenced by thetype of sulfur bridge, the structural features, and the storage conditions.Our results suggest appropriate protection of the phenolic OH of ETPswould improve various pharmaceutically relevant properties, includingbioavailability.

Automated summary

In this study, we used DFT calculations to investigate the degradation pathways of ETPs with transannular disulfide bridge. Our findings suggest that the chemical stability of ETPs is influenced by the sulfur bridge type, structural features, and storage conditions. Protecting the phenolic OH of ETPs could improve their bioavailability and other pharmaceutically relevant properties.