title: Traceless Solid-Phase α-Hydroxytropolone 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.
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: D'Erasmo
authors.affiliation: Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Masaoka
authors.affiliation: Molecular Targets Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wilson
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA.
authors.forename: Errol M
authors.initials: EM
authors.lastname: Hunte
authors.affiliation: Molecular Targets Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Beutler
authors.affiliation: Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: Stuart F J
authors.initials: SF
authors.lastname: Le Grice
authors.affiliation: 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.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Murelli