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; Amy E. Mercer; Gemma Nixon; Paul A. Stocks; Paul M. O'Neill

doi:10.1039/b924319d

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, Amy E. Mercer, Gemma Nixon, Paul A. Stocks, Paul M. O'Neill

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2068-2077
Number of pages	10
Journal	Organic and Biomolecular Chemistry
Volume	8
Issue number	9
DOIs	https://doi.org/10.1039/b924319d
Publication status	Published - 2010
Externally published	Yes

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Amewu, R., Gibbons, P., Mukhtar, A., Stachulski, A. V., Ward, S. A., Hall, C., Rimmer, K., Davies, J., Vivas, L., Bacsa, J., Mercer, A. E., Nixon, G., Stocks, P. A., & O'Neill, P. 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 and Biomolecular Chemistry, 8(9), 2068-2077. https://doi.org/10.1039/b924319d

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title = "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",

abstract = "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.",

author = "Richard Amewu and Peter Gibbons and Amira Mukhtar and Stachulski, {Andrew V.} and Ward, {Stephen A.} and Charlotte Hall and Karen Rimmer and Jill Davies and Livia Vivas and John Bacsa and Mercer, {Amy E.} and Gemma Nixon and Stocks, {Paul A.} and O'Neill, {Paul M.}",

year = "2010",

doi = "10.1039/b924319d",

language = "English",

volume = "8",

pages = "2068--2077",

journal = "Organic and Biomolecular Chemistry",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

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}

Amewu, R, Gibbons, P, Mukhtar, A, Stachulski, AV, Ward, SA, Hall, C, Rimmer, K, Davies, J, Vivas, L, Bacsa, J, Mercer, AE, Nixon, G, Stocks, PA & O'Neill, PM 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 and Biomolecular Chemistry, vol. 8, no. 9, pp. 2068-2077. https://doi.org/10.1039/b924319d

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 et al.
In: Organic and Biomolecular Chemistry, Vol. 8, No. 9, 2010, p. 2068-2077.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Amewu, Richard

AU - Gibbons, Peter

AU - Mukhtar, Amira

AU - Stachulski, Andrew V.

AU - Ward, Stephen A.

AU - Hall, Charlotte

AU - Rimmer, Karen

AU - Davies, Jill

AU - Vivas, Livia

AU - Bacsa, John

AU - Mercer, Amy E.

AU - Nixon, Gemma

AU - Stocks, Paul A.

AU - O'Neill, Paul M.

PY - 2010

Y1 - 2010

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AB - 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.

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U2 - 10.1039/b924319d

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M3 - Article

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AN - SCOPUS:77951103171

SN - 1477-0520

VL - 8

SP - 2068

EP - 2077

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 9

ER -

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

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