Synfacts 2019; 15(11): 1215
DOI: 10.1055/s-0039-1691017
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Nanomolar Inhibitor of Trypanosoma brucei Trypanothione Reductase

Philip Kocienski
De Gasparo R, Halgas O, Harangozo D, Kaiser M. * Pai EF. * Krauth-Siegel RL, Diederich F. * ETH Zurich, Switzerland
Targeting a Large Active Site: Structure-Based Design of Nanomolar Inhibitors of Trypanosoma brucei Trypanothione Reductase.

Chem. Eur. J. 2019;
25: 11416-11421
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18. Oktober 2019 (online)



The parasitic protozoa responsible for trypanosomiasis, Chagas’ disease, and leishmaniasis require the reduction of trypanothione disulfide to trypanothione, which the parasites use in several essential processes. Target molecule N is the strongest competitive inhibitor in vitro of trypanothione reductase from Trypanosoma cruzi reported to date.



Note the construction of highly hindered amine E by nucleophilic substitution of benzotriazole from N,N-acetal B by the organomagnesium reagent D.



For a Review on properties and synthetic utility of N-substituted benzotriazoles, see A. R. ­Katritzky, X. Lan, J. Z. Yang Chem. Rev. 1998, 98, 409–548.