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Bioorganic & medicinal chemistry letters DOI:10.1016/j.bmcl.2008.10.083

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

Publication TypeJournal Article
Year of Publication2008
AuthorsMartyn, DC, Ramirez, AP, Beattie, MJ, Cortese, JF, Patel, V, Rush, MA, Woerpel, KA, Clardy, J
JournalBioorganic & medicinal chemistry letters
Volume18
Issue24
Pages6521-4
Date Published2008/12/15
ISSN0960-894X
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).

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0960-894X(08)01237-7
DOI10.1016/j.bmcl.2008.10.083
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/18993067?dopt=Abstract