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.
D'Erasmo, Michael P.,Masaoka, Takashi,Wilson, Jennifer A.,Hunte, Errol M.,Beutler, John A.,Le Grice, Stuart F. J.,Murelli, Ryan P.
supporting information
p. 1789 - 1792
(2016/09/23)
Re-examination of nucleophilic substitution in chlorokojic acid
Chlorokojic acid was reacted with S2O23 , NO-3 , N-3 , I- , and SCN- . Only the three latter nucleophiles substituted the chlorine atom in the 2-CH2/s
Uher, Michal,Szymońska, Joanna,Korenova, Anna,Tomasik, Piotr