2. Academic Validation
  3. Traceless Solid-Phase α-Hydroxytropolone Synthesis

Traceless Solid-Phase α-Hydroxytropolone Synthesis

  • Medchemcomm. 2016 Sep 1;7(9):1789-1792. doi: 10.1039/C6MD00237D.
Michael P D'Erasmo 1,  Takashi Masaoka 2,  Jennifer A Wilson 3,  Errol M Hunte Jr 4,  John A Beutler 3,  Stuart F J Le Grice 2,  Ryan P Murelli 1
Affiliations

Affiliations

  • 1 Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, NY, USA.
  • 2 Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA.
  • 3 Molecular Targets Laboratory, National Cancer Institute, Frederick, MD, USA.
  • 4 Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA.
PMID: 28090282 DOI: 10.1039/C6MD00237D
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.

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