Design, Synthesis and Antimalarial Activity of Trifluoromethylartemisinin-Mefloquine Dual Molecules

International audienc

Aminated compounds bearing at least allyl and difluoromethyl groups and a method for their synthesis: WO 2003095415, Rhodia Chimie, Fr.

Rhodia Chimie, Fr.) PCT Int. Appl; N°Brevet :WO 2003095415info:eu-repo/semantics/publishe

Chemoselective synthesis of trifluoromethylvinyl sulfoxides and sulfones through oxidation of corresponding sulfides

At low temperatures, perfluoro-cis-2,3-dialkyloxaziridines 4 oxidize 1-trifluoromethylvinyl sulfides 1 to the corresponding sulfoxides 2 in quantitative yields. By using 3-chloroperoxybenzoic acid, or the same oxaziridines at room temperature, sulfones 3 are formed exclusively

Stereoselective Barbier-Type Allylation Reaction of Trifluoromethyl Aldimines

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Fluoroartemisinin: Trifluoromethyl Analogues of Artemether and Artesunate

International audienc

Transport of fluoroalkyl dihydroartemisinin derivatives across rat intestinal tissue

Artemisinin and its derivatives represent an important class of antimalarials. In order to obtain new derivatives with a longer half-life and better bioavailability, the development of fluorinated analogues has received increasing attention. The purpose of this study was to investigate the permeation of artemisinin and of two fluoroalkyl derivatives of dihydroartemisinin (DHA), namely 10beta-(trifluoropropyloxy)dihydroartemisinin (F(1)-DHA) and 10-trifluoromethyl-16-[2-(hydroxyethyl)piperazine] (F(2)-DHA), across rat intestine using Ussing diffusion chambers. Further, the saturation solubility and partition coefficient of the compounds were determined in order to determine whether the substitution of hydrogen atoms by fluorine can induce great changes in these molecular properties. Artemisinin and F(2)-DHA permeability coefficients of 27.5 +/- 1.6 and 23.2 +/- 1.2 (x 10(-6), cm s(-1)), respectively, are predictive of good oral absorption. This indicates that the introduction of a fluoroalkyl group in a compound such as artemisinin in order to prolong its half-life does not constitute an obstacle for its absorption after oral administration. Moreover, the introduction of a polar substituent into the DHA structural scaffold increased the aqueous solubility of F(2)-DHA relative to artemisinin. F(1)-DHA permeability measurements showed low transepithelial diffusion across the intestinal mucosa. This indicates that the introduction of a fluorinated substituent at the alpha-methylene carbon of DHA ethers in order to provide protection against oxidative processes constitutes an obstacle for the absorption after oral administration

Synthesis and antimalarial activities of novel 3,3,6,6-tetraalkyl-1,2,4,5-tetraoxanes

International audienc

A crystalline H-bond cluster of hexafluaroisopropanol (HFIP) and piperidine : Structure determination by X ray diffraction

International audiencePiperidine and 1,1,1-3,3,3 hexafluoro-2-propanol (HFIP) have been co-crystallized and X-ray crystal structure has been explored. Single-crystal X-ray analysis displays the existence of hydrogen bonding aggregates through dimers 1 of the complex (one piperidine/two HFIP) where the heteroatoms form a six-center ring. In this cluster 1, each heteroatom (N, O) is multiple H-bond donor and acceptor. Surprisingly the strongest H-bond of the network is where HFIP acts as an acceptor from the amine. In this complex HFIP adopts a conformation different from that of HFIP aggregates. The supramolecular architecture is also based on discrimination between polar and hydrophobic parts that allows the alignment of molecules and the formation of parallel channels. NMR experiments show that strong interactions between piperidine and HFIP are maintained in solution

Microbial reduction of α,α,α-trifluoro-α′-sulfenylketones

Several microorganisms have been employed in the reduction of two α,α,α-trifluoro-α′-sulfenylketones. Some of them produce corresponding alcohols in high diastero- and enantioselection, the high conversion in a single enantiomer being secured by the racemization of starting ketones in the biotransformation conditions. Transformation of obtained sulfenyl-trifluoromethyl-alcohols into trifluoromethyl-epoxides is also described