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.
Amewu, Richard;
Gibbons, Peter;
Mukhtar, Amira;
Stachulski, Andrew V;
Ward, Stephen A;
Hall, Charlotte;
Rimmer, Karen;
Davies, Jill;
Vivas, Livia;
Bacsa, John;
+4 more...Mercer, Amy E;
Nixon, Gemma;
Stocks, Paul A;
O'Neill, Paul M;
(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: https://doi.org/10.1039/b924319d
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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.
