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Diels-Alder/thiol-olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore

O'Neill, P. M., Verissimo, E., Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192, Davies, Jill, Korshin, E. E., Araujo, N., Pugh, M. D., Cristiano, M. L. S., Stocks, Paul A. and Bachi, M. D. (2006) 'Diels-Alder/thiol-olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore'. Bioorganic & Medicinal Chemistry Letters, Vol 16, Issue 11, pp. 2991-2995.

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Abstract

A Diels-Alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides. (c) 2006 Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: artemisinin arteflene endoperoxide malaria mechanism of action beta-sulfonyl-endoperoxides yingzhaosu-a analogs plasmodium-falciparum malaria parasites peroxides artemisinins monoterpenes mechanism arteflene design
Subjects: QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1016/j.bmcl.2006.02.059
Depositing User: Martin Chapman
Date Deposited: 13 Jun 2011 14:37
Last Modified: 06 Feb 2018 13:02
URI: https://archive.lstmed.ac.uk/id/eprint/1568

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