Henri Moskowitz

Structure–Activity Relationships of Synthetic Tricyclic Trioxanes Related to Artemisinin: The Unexpected Alkylative Property of a 3‐(Methoxymethyl) Analog

A clear-cut correlation between antimalarial potency and the alkylative property of synthetic tricyclic trioxanes 5–10 is reported. Thus, trioxanes 5 and 7, substituted at the C-5a angular position by a methyl or a cyano group, proved to be completely devoid of antimalarial activity, and did not alkylate the heme model MnIITPP. In contrast, both the anti-Plasmodium activity and the alkylative property were restored in the C-5a-unsubstituted analog 8, bearing a methoxymethyl group at C-3. Reaction of 8 with MnIITPP furnished the covalent adduct 18, resulting from trapping of the methoxymethyl radical by the heme model. All these results reinforce the hypothesis that the metalloporphyrin closely interacts with the peroxide bond of the drug to bring about activation of these trioxane antimalarial agents.

Selective γ-1,4 addition of methoxyallylcopper to enone

Abstract Methylallylether is deprotonated by sec -butyllithium and treated with copper (I) iodide in dimethylsulfide to afford the corresponding allylcopper reagent. This ambident nucleophile adds in highly γ-1,4 selectivity to several enones and the corresponding ketoenolethers are obtained in good yields.

Synthese de tetrahydrodibenzofurannes : creation d'un carbone quaternaire par transposition de claisen.

Abstract A new route to tetrahydrodibenzofurannes is described. It is based upon Claisen transposition of an aryloxycyclohexene to o .hydroxyphenyl cyclohexene which is, in turn, cyclized by palladium acetate. In the studied example, an overall yield of 45 % is obtained in two steps. The isolation of an unexpected minor isomeric transposed compound sets a problem of mechanism.

γ-1, 4 Addition of substituted methoxyallylcopper reagents to methylvinylketone

Abstract Methoxyallylcopper reagents substituted in α and/or β position of methoxy group reacted regiospecifically with MVK to give γ-1, 4 adducts, i.e. ketoenolethers. γ substituted methoxyallylcopper reagents gave mixtures of γ-1, 4 and α-1, 4 adducts. Download full-size image