Antimalarial Cyclic Peroxide Lactones.
Abstract
Bruceoside-A acetonide was synthesized by an acid-catalyzed transacetalization of bruceoside-A and acetaldehyde diethyl acetal. Brusatolyl-1-nonenoate was synthesized from brusatol, obtained by acid hydrolysis of bruceoside-A, by an initial protection of the 3-hydroxyl group as a dimethyl-t-butylsilyl ether followed by base hydrolysis of the C-15 ester side chain, reacylation with 1-nonenoyl chloride and deblocking of the silyl moiety with tetrabutylammonium fluoride. Bruceoside-A was obtained directly by extraction of Brucea javanica (Simaroubaceae). The synthesis of 2,5-alpha-peroxy-6, 11 Beta H-eudesm-3-en-6,13-olide involved the reduction of 1,2-dihydro-alpha-santonin, prepared to a 3-hydroxy derivative. Subsequent conversion of this derivative to 6,11 Beta H-eudesm-2,4-dien-6,13-olide via a 3-0-mesyl intermediate, followed by photooxygenation gave rise to the desired cyclic peroxide lactone. Evaluation of these novel compounds as potential antimalarial drugs by Walter Reed Army Institute of Research is currently in progress.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 13, 1984
- Accession Number
- ADA168091
Entities
People
- Kuo-hsiung Lee
Organizations
- University of North Carolina at Chapel Hill