Mechanistic Investigation of the Degradation Pathways of α-β/α-α Bridged Epipolythiodioxopiperazines (ETPs).

Epipolythiodioxopiperazines (ETPs) make up a class of biologically active fungal metabolites with a transannular disulfide bridge. In this work, we used DFT calculations to examine in detail the degradation (desulfurization) pathways of α-β/α-α bridged ETPs. The chemical stability of ETPs is influenced by the type of sulfur bridge, the structural features, and the storage conditions. Our results suggest appropriate protection of the phenolic OH of ETPs would improve various pharmaceutically relevant properties, including bioavailability.