Traceless solid-phase α-hydroxytropolone synthesis. Issue 9 (18th July 2016)

• Record Type: Journal Article
• Authors: D'Erasmo, Michael P.; Masaoka, Takashi; Wilson, Jennifer A.; Hunte, Errol M.; Beutler, John A.; Le Grice, Stuart F. J.; Murelli, Ryan P.
• Is Part Of: MedChemComm. Volume 7:Issue 9(2016:Sep.)
• Page Start: 1789
• Page End: 1792
• Publication Date: 2016-07-18
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00237d
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : α-Hydroxytropolones are established inhibitors of several therapeutically relevant binuclear metalloenzymes. A solid-phase adaptation to an oxidopyrylium cycloaddition/ring-opening procedure is described that allows for rapid parallel synthesis. Abstract : α-Hydroxytropolones are established inhibitors of several therapeutically relevant binuclear metalloenzymes, and thus lead drug targets for various human diseases. We have leveraged a recently-disclosed three-component oxidopyrylium cycloaddition in the first solid-phase synthesis of α-hydroxytropolones. We also showed that, while minor impurities exist after cleavage and aqueous wash, the semi-crude products display activity in HIV RT-associated RNaseH enzymatic and cell-based assays consistent with pure molecules made in solution phase. These proof-of-principle studies demonstrate the feasibility of solid-phase α-hydroxytropolone synthesis and its potential to serve as a powerful platform for α-hydroxytropolone-based drug discovery and development.