J. Mayrargue

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.

Synthesis of Piperidine Derivatives by Reduction of Pyridinium Salts

Abstract Piperidine derivatives 1a–e and 2a–f have been prepared by the reduction of 3‐and 4‐substituted pyridinium salts with NaBH4 in moderate to excellent yields. The reactions regioselectively give 1,2,5,6‐tetrahydropyridines, and the yields depend greatly upon the nature of substituents on the phenyl ring and on the nitrogen atom, the nature and the position of the substituents on the pyridyl ring, and the chain length between the aryloxy and the pyridyl groups.

Enehydrazines derivees de la pyrazoline

Abstract Two cyclic enehydrazines are synthesized from acetylenic epoxides : one of them is stable, the other one, not isolable, duplicates to a tricyclic spiran whose structure is discussed.