Synthesis of spiro-1,2-dioxolanes and their activity against Plasmodium falciparum.

Bioorg Med Chem Lett
Authors
Keywords
Abstract

Artemisinin-derived compounds play an integral role in current malaria chemotherapy. Given the virtual certainty of emerging resistance, we have investigated spiro-1,2-dioxolanes as an alternative scaffold. The endoperoxide functionality was generated by the SnCl(4)-mediated annulation of a bis-silylperoxide and an alkene. The first set of eight analogs gave EC(50) values of 50-150 nM against Plasmodium falciparum 3D7 and Dd2 strains, except for the carboxylic acid analog. A second series, synthesized by coupling a spiro-1,2-dioxolane carboxylic acid to four separate amines, afforded the most potent compound (EC(50) approximately 5 nM).

Year of Publication
2008
Journal
Bioorg Med Chem Lett
Volume
18
Issue
24
Pages
6521-4
Date Published
2008 Dec 15
ISSN
1464-3405
URL
DOI
10.1016/j.bmcl.2008.10.083
PubMed ID
18993067
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