Jean-Gérard Wolf

Un derive à double liaison phosphore-arsenic : le premier phospha-arsene stable

Summary The first compound with a phosphorus-arsenic double bond, the phospha-arsene (Me 3 Si) 3 C-P=As-C(SiMe 3 ) 3 5 has been isolated and characterized by its physico-chemical chemical data; it reacts with sulphur leading to a novel heterocycle, the phospharsatiiran Download full-size image 6 .

Contribution of Dithiol Ligands to In Vitro and In Vivo Trypanocidal Activities of Dithiaarsanes and Investigation of Ligand Exchange in an Aqueous Solution

ABSTRACT Twelve new dithiaarsanes were evaluated for their in vitro and in vivo trypanocidal properties in regard to their three parent molecules, 4-amino-phenylarsenoxide, melarsenoxide, and 4-dansylamino-phenylarsenoxide. The most potent dithiaarsane, compound 2b, had a minimum effective concentration of 1.5 nM after 48 h of incubation and at a dose of 0.39 μmol/kg of body weight (0.2 mg/kg) administered subcutaneously cured 100% of mice acutely infected withTrypanosoma brucei brucei CMP. With this model, the chemotherapeutic index of compound 2b was 512, compared to 256 for melarsamine dihydrochloride (Cymelarsan) under the same conditions. With a chronic infection produced by T. brucei brucei GVR, compound 2b cured 100% of mice after treatment at a dose of 25 μmol/kg (12.5 mg/kg) for 4 consecutive days, whereas melarsamine dihydrochloride and potassium melarsonyl (Trimelarsan) cured less than 50% mice at this dose. For both acute and late-stage infections, dithiaarsanes having a melaminophenyl ring exhibited the most-potent trypanocidal activity. Compound 2b is thus one of the most active organoarsenicals described in a mouse trypanosomiasis model. Considering that the main intracellular targets of organoarsenicals are thiol groups, we studied the possibility of ligand exchange between Cymelarsan and several dithiols. In aqueous solution, we observed a rapid exchange of cysteamine from melarsamine with free cysteamine and also with various dithiols always in favor of more stable cyclic derivatives. These ligand exchanges suggest the ability of trivalent organoarsenicals to react with targets such as trypanothione and dihydrolipoic acid. Among several ligands, a 1,3-dimercaptopropane moiety appeared the most suitable for trypanocidal activity.

A synthetic pathway to macrocyclic and optically active pentamethinium salts

Abstract The design of new types of azodyes with optical activity and macrocyclic structure was achieved by the generalization of the reaction of stabilized carboxonium ions with various primary and secondary amino compounds.

NEW DIAZA PENTADIENYLIUM SALTS (CYANINE DYES) DERIVED FROM N-SILYLATED PHOSPHINIMINES AND GUANIDINES

Abstract New synthetic methods for the preparation of pentadienylium cations (cyanine dyes) are developed in our laboratories. In particular the reaction of carboxonium derivatives on various primary and secondary amines is to be emphasized. This method is remarkably versatile to lead to new dyes hardly obtainable otherwise. It is applied here to the synthesis of previously unknown derivatives of N-silylated phosphinimines and guanidines where the conjugated polyenic system can be extended over the nitrogen atom on the phosphinimine or guanidine moiety. Spectrochemical results, mainly 31P, 13C NMR and UV are in accordance with these assumptions opening thus a new field of investigation for the reactivity of the aza-Wittig compounds and more generally for the physical applications (ie in optical devices).

Structure of the Cycloaddition Products of Pyrido[2,1-a]isoindole with Maleimide Derivatives: X-ray Diffraction Analysis and1H NMR Variable-Temperature Spectra

Investigation of the cycloaddition reaction under thermodynamic control of pyrido[2,1-a]isoindole with maleimide derivatives revealed a new rearrangement leading to 2-{2′-[(1R)2,5-dioxopyrrolidinylidene]-2′-[(1R)-2,5-dioxopyrrolidinyl)methyl]}phenylpyridine. Their structure was confirmed by X-ray diffraction analysis. The atropisomeric properties of the obtained compounds were examined in a detailed NMR spectroscopic study. Dependence of the spectra on temperature was investigated, and coalescence temperatures and conversion barriers between the corresponding atropisomers determined.

Newly substituted pentamethine merocyanines. Part 1: Synthesis, physical properties, and synthetic applications

Abstract New 1,5-substituted pentamethine merocyanine dyes were synthesised in high yields. Their reaction towards acid chlorides or anhydrides leads to new hemicarboxonium salts with enhanced reactivity due to their better leaving groups. They are able to combine with soft nucleophiles to obtain a new cyanine dyes series. Thus, these merocyanines may be used as stable intermediate reagents in cyanine synthesis. Moreover, from a theoretical point of view, the synthesis of substituted derivatives of the well-known polyenic donor acceptor models for non-linear optics, opens the route to physicochemical determinations of their effects on the polarisation of the chain and the bond length alternation (Part 2 of study in progress).

The synthesis of pentadienylium salts via reactions of (5-ethoxy-1,5-diaryl-2,4-pentadienylidene)ethyloxonium perchlorate with hydrazines

Reaction of the readily available (5-ethoxy-1,5-diaryl-2,4-pentadienylidene)ethyloxonium perchlorate 1 with hydrazines, R2NNH2 or RNHNH2,provides a simple and efficient synthesis of previously unknown (5-ethoxy-1,5-diaryl-2,4-pentadienylidene)hydrazinium salt 2a-d. Application of this method to be synthesis of the highly conjugated pentadienylium salt from terephthalic dihydrazide is reported.

Derives organiques de l'arsenic dicoordine synthese et caracterisation de nouveaux cations arsenium possedant l'enchainement N-As-N

Abstract Four new cyclic and acyclic dicoordinated arsenium salts were obtained by action of AlCl3 and CF3SO3SiMe3 (or CF3SO3inAg) on tricoordinated chloroarsenic precursors.

Conversions of 2-(2-Oxo Cyclohexylcarbonyl)Benzoic Acid Derivatives to Pyrazolo[ [5] , [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] ]Isoindole and Pyrimidine Rings

Abstract Phtalic acid derivative of o-methylcarboxybenzoylchloride readily acylates N(1-cyclohexenyl) morpholine and is likely to acylate other enamines along the classic path to 1,3-diketones. It is a convenient route towards o-(1-(1,3-diketone)) derivatives of benzoic acid, which are precursors of o-(heteroaryl)-benzoic acids. Further conversions with hydrazines and amidines lead to pyrazolo[ [5] , [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] ]isoindole and pyrimidine rings respectively. The structures of the obtained compounds were confirmed by X-ray structure determinations.

Une nouvelle classe de composés anti-parasitaires: les spiroarsoranes. Evaluation in vitro sur la filaire Molinema dessetae

Resume Une nouvelle classe de composes biologiquement actifs, les «spiroarsoranesa a ete synthetisee et leur activite testee in vitro sur la filaire Molinema dessetae . Une importante activite filaricide a pu etre ainsi demontree, avec une faible toxicite.