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

Daiki Kurita; Hajime Sato; Kazunori Miyamoto; Masanobu Uchiyama

doi:10.1021/acs.joc.3c01061

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

J Org Chem. 2023 Sep 1;88(17):12797-12801. doi: 10.1021/acs.joc.3c01061. Epub 2023 Aug 13.

Authors

Daiki Kurita¹, Hajime Sato², Kazunori Miyamoto¹, Masanobu Uchiyama^{1

3}

Affiliations

¹ Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi 400-8510, Japan.
³ Research Initiative for Supra-Materials (RISM), Shinshu University, 3-15-1 Tokida, Ueda, Nagano 386-8567, Japan.

PMID: 37574909
DOI: 10.1021/acs.joc.3c01061

Abstract

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.