Jump to main content
Jump to site search

Issue 9, 2016
Previous Article Next Article

Traceless solid-phase α-hydroxytropolone synthesis

Author affiliations

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.

Graphical abstract: Traceless solid-phase α-hydroxytropolone synthesis

Back to tab navigation

Supplementary files

Publication details

The article was received on 28 Apr 2016, accepted on 05 Jul 2016 and first published on 07 Jul 2016


Article type: Research Article
DOI: 10.1039/C6MD00237D
Author version available: Download Author version (PDF)
Citation: Med. Chem. Commun., 2016,7, 1789-1792
  •   Request permissions

    Traceless solid-phase α-hydroxytropolone synthesis

    M. P. D'Erasmo, T. Masaoka, J. A. Wilson, E. M. Hunte, J. A. Beutler, S. F. J. Le Grice and R. P. Murelli, Med. Chem. Commun., 2016, 7, 1789
    DOI: 10.1039/C6MD00237D

Search articles by author

Spotlight

Advertisements