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Updated: Feb 1, 2026

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Published on: December 23, 2016
Reducing Holomycin Thiosulfonate to its Disulfide with Thiols
Andrew N Chan1, Walter J Wever2, Elisabetta Massolo1
1Department of Chemistry , University of North Carolina at Chapel Hill , CB #3290, Chapel Hill , North Carolina 27599 , United States.
Abstract:
The dithiolopyrrolone (DTP) natural products contain a unique ene-disulfide that is essential for their antimicrobial and anticancer activities. The ene-disulfide in some DTPs is oxidized to a cyclic thiosulfonate, but it is unknown how the DTP thiosulfonates react with biomolecules. We studied the reactivity of the thiosulfonate derivative of the DTP holomycin, oxo-holomycin, and discovered a unique redox reaction: Oxo-holomycin is reduced to its parent disulfide, while oxidizing small molecule and protein thiols to disulfides. Our work reveals that the DTP core is a privileged scaffold that undergoes unusual redox chemistry. The redox chemistry of the DTP natural products may contribute to their mechanism of action.
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