Synthesis and Electrochemical Studies of New Antimalarial Endoperoxides

Najjar, Fadia; Baltas, Michel; Gorrichon, Liliane; Moreno, Yolande; Tzedakis, Théodore; Vial, Henri; André-Barrès, Christiane

doi:10.1002/ejoc.200300165

Cited by 36 publications

(29 citation statements)

References 22 publications

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“…[11] These were separated by column chromatography and individually methylated with butyllithium and methyl trifluoromethanesulfonate at low temperature to give the endoperoxides 10a and 10b, respectively, bearing the crucial ether function, in 72-78 % yields.…”

Section: Resultsmentioning

confidence: 99%

“…Some previously synthesized derivatives show moderate to good antimalarial activities. [11] We have previously reported the crucial role of the peroxyketal function for this activity, [12][13][14] but the most significant differences were those observed between the natural mation of a 1,2-dioxetane. Its decomposition gave aldehyde 12 and 4-hydroxybutan-2-one; these compounds were also identified when acidic conditions were used in the deprotection step.…”

Section: Introductionmentioning

confidence: 99%

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New Amino Endoperoxides Belonging to the Antimalarial G‐Factor Series

Givelet¹,

Bernat²,

Mathieu³

et al. 2007

Eur J Org Chem

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In the search for new antimalarial endoperoxides we developed a direct route for the preparation of new amino compounds belonging to the G-factor series. During the synthesis, a significant difference in reactivity between two series of diastereoisomers was observed. The final amino endoperoxides were obtained with 58 to 70 % yields, depending on the starting amine, in the "anti" series, but with the "syn" diastereoisomers an unexpected rearrangement occurred during the deprotection step. This was attributed to a transient hexacoordinate fluorosilicon complex allowing the for-

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New Amino Endoperoxides Belonging to the Antimalarial G‐Factor Series

Givelet¹,

Bernat²,

Mathieu³

et al. 2007

Eur J Org Chem

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“…The G factors were first isolated from Eucalyptus grandis (Ghisalberti 1996) where they act as phytohormones and seem to be involved in frost resistance and water loss reduction. Also in this case, a series of synthetic analogues have been prepared (Najjar et al 2003). In particular, it is interesting to notice that, based on previously reported structure-activity relationships (Posner et al 1998), the peroxyhemiketal hydroxyl was methylated, yielding more active peroxyketal compounds (e.g.…”

Section: Artemisinin and Other Terrestrial Antimalarial Endoperoxidesmentioning

confidence: 99%

Marine endoperoxides as antimalarial lead compounds

Fattorusso

Taglialatela‐Scafati

2010

Phytochem Rev

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Malaria, a pathology caused by protozoa belonging to the genus Plasmodium, is one of the major threats to global health, with about 300-500 million new clinical cases occurring every year and 1-3 million annual deaths. The recrudescence in the number of fatal cases registered in recent years can be attributed to the diffusion of multi-drug resistant strains of Plasmodium, which make less effective the limited armamentarium of available drugs. Living organisms are a recognized source of potentially bioactive molecules and, among them, marine natural products are emerging as one of the most interesting sources to be exploited for the discovery of new antimalarial compounds. In this article we will report results obtained for a single class of marine metabolites, namely endoperoxide-containing derivatives. Many of these molecules possess a simple six-membered 1,2-dioxygenated ring bearing two or three alkyl/aryl groups of different complexity. They can be divided according to the group linked at one of the two endoperoxide-oxygen bearing carbons: peroxyketal derivatives (methoxy group) or non-peroxyketal derivatives (methyl/ethyl groups). Molecules belonging to these classes show in vitro antimalarial activity in the nanomolar range on chloroquine-resistant strains. A number of investigations gave insights into the mechanism of action of these molecules, suggesting structural changes to optimize their antimalarial activity

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“…For example, 2-alkylidenecyclohexane-1,3-diones 92-keto add oxygen across the diene system of 92-enol without irradiation to give the fused bicyclic peroxides 93 in excellent yields (Scheme 19) 89,90 . Pursuing a similar approach, syncarpic acid (94) was efficiently converted, via intermediates 95 and 96, into the natural product, G3 factor endoperoxide (97a), and into its analogues 97b and 97c, which exhibit antimalarial activity (Scheme 20) 91,92 . Unsaturated ketones of type trans-98, possessing just one carbonyl group, are less active toward molecular oxygen and their peroxidation requires sensitizers and sun-lamp irradiation.…”

Section: Phmentioning

confidence: 99%