Synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (TOCO) of allylic alcohols.
Richard Amewu;
Peter Gibbons;
Amira Mukhtar;
Andrew V Stachulski;
Stephen A Ward;
Charlotte Hall;
Karen Rimmer;
Jill Davies;
Livia Vivas;
John Bacsa;
+4 more...
Amy E Mercer;
Gemma Nixon;
Paul A Stocks;
Paul M O'Neill;
(2010)
Synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (TOCO) of allylic alcohols.
Organic & biomolecular chemistry, 8 (9).
pp. 2068-2077.
ISSN 1477-0520
DOI: 10.1039/b924319d
Thiol-Olefin Co-Oxygenation (TOCO) methodology has been applied to the synthesis of a small library of weak base and polar 1,2,4-trioxanes. The 1,2,4-trioxane units synthesised exhibit remarkable stability as they survive base catalysed hydrolysis and mixed anhydride/amine coupling reactions. This unique stability feature has enabled a range of novel substitution patterns to be incorporated within the spiro 1,2,4-trioxane unit. Selected analogues express potent in vitro nM antimalarial activity, low cytotoxicity and oral activity in the Plasmodium berghei mouse model of malaria.
Item Type | Article |
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Keywords | highly stereoselective-synthesis, antiproliferative activity, bicyclic, peroxides, artemisinin, derivatives, drug, methodology, malaria, design, potent |
ISI | 276786000013 |