Application of thiol-olefin co-oxygenation methodology to a new synthesis of the 1,2,4-trioxane pharmacophore

Paul M O'Neill; Amira Mukhtar; Stephen A Ward; Jamie F Bickley; Jill Davies; Mario D Bachi; Paul A Stocks

doi:10.1021/ol0492142

Application of thiol-olefin co-oxygenation methodology to a new synthesis of the 1,2,4-trioxane pharmacophore

Org Lett. 2004 Sep 2;6(18):3035-8. doi: 10.1021/ol0492142.

Authors

Paul M O'Neill¹, Amira Mukhtar, Stephen A Ward, Jamie F Bickley, Jill Davies, Mario D Bachi, Paul A Stocks

Affiliation

¹ Department of Chemistry, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK. p.m.oneill01@liv.ac.uk

PMID: 15330581
DOI: 10.1021/ol0492142

Abstract

[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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkenes / chemistry*
Alkenes / pharmacology
Antimalarials / chemical synthesis*
Antimalarials / pharmacology
Combinatorial Chemistry Techniques
Heterocyclic Compounds / chemical synthesis*
Heterocyclic Compounds / pharmacology
Molecular Structure
Oxidation-Reduction
Sulfhydryl Compounds / chemistry*
Sulfhydryl Compounds / pharmacology

Substances

1,2,4-trioxane
Alkenes
Antimalarials
Heterocyclic Compounds
Sulfhydryl Compounds
s-trioxane