Application of thiol-olefin co-oxygenation methodology to a new synthesis of the 1,2,4-trioxane pharmacophore.
[reaction: see text] Thiol-olefin co-oxygenation (TOCO) of substituted allylic alcohols generates alpha-hydroxyperoxides that can be condensed in situ with various ketones to afford a series of functionalized 1,2,4-trioxanes in good yields. Manipulation of the phenylsulfenyl group in 4a allows for convenient modification to the spiro-trioxane substituents, and we describe, for the first time, the preparation of a new class of antimalarial prodrug.
O'Neill
Paul M
PM
Department of Chemistry, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK. p.m.oneill01@liv.ac.uk
Mukhtar
Amira
A
Ward
Stephen A
SA
Bickley
Jamie F
JF
Davies
Jill
J
Bachi
Mario D
MD
Stocks
Paul A
PA
D000475:Alkenes / Q000737:chemistry* / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology
C503429:1,2,4-trioxane; D000475:Alkenes; D000962:Antimalarials; D006571:Heterocyclic Compounds; D013438:Sulfhydryl Compounds; C011374:s-trioxane