Guy Lemière

Selective palladium-catalyzed aminations on dichloropyridines

Abstract Palladium-catalyzed amination proved to be a valuable strategy for the selective introduction of aromatic and heteroaromatic amines, including aminopyridines and aminodiazines, on dichloropyridines. The use of mild amination conditions resulted in maximum selectivity and excellent base sensitive functional group tolerance.

Synthesis and antiplasmodial activity of aminoalkylamino-substituted neocryptolepine derivatives.

A series of chloro- and aminoalkylamino-substituted neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives were synthesized and evaluated as antiplasmodial agents. The evaluation also included cytotoxicity (MRC5 cells), inhibition of beta-hematin formation, and DNA interactions (DNA-methyl green assay). Introduction of aminoalkylamino chains increased the antiplasmodial activity of the neocryptolepine core substantially. The most efficient compounds showed antiplasmodial activities in the nanomolar range. N(1),N(1)-Diethyl-N(4)-(5-methyl-5H-indolo[2,3-b]quinolin-8-yl)pentane-1,4-diamine 11c showed an IC(50) of 0.01 microM and a selectivity index of 1800.

3′,4-Di-O-methylcedrusin: synthesis, resolution and absolute configuration

The title compound has been synthesised in racemic form by a biomimetic reaction sequence. The two enantiomers were resolved by column chromatography of one of the synthetic intermediates. On the basis of CD results a tentative absolute configuration for the synthetic enantiomers and natural 3′,4-di-O-methylcedresin is proposed.

The first tandem double palladium-catalyzed aminations: synthesis of dipyrido[1,2-a∶3′,2′-d]imidazole and its benzo- and aza-analogues

A new strategy for the synthesis of the title compounds via a regio- and chemoselective one-pot inter- and intramolecular Buchwald-Hartwig amination of 2-chloro-3-iodopyridine with aminoazines and -diazines is reported.

Suzuki reactions on chloropyridazinones: an easy approach towards arylated 3(2H)-pyridazinones

Abstract The synthesis of 4-aryl-5-methoxy-, 5-aryl-4-methoxy- and 4,5-diaryl-3(2H)-pyridazinones via Suzuki palladium-catalysed cross-coupling reactions with the corresponding chloro-3(2H)-pyridazinones is described.

A new approach towards the synthesis of 3-amino-6-(hetero)arylpyridazines based on palladium catalyzed cross-coupling reactions

The synthesis of 3-amino-6-(hetero)arylpyridazines via palladium catalyzed cross-coupling reactions (Suzuki, Stille) on 3-amino-6-chloropyridazine (1a) and 3-amino-6-iodopyridazine (1b) has been investigated. Comparison of the results shows that there is no need to start from 1b. An improved method for the synthesis of compound 1b from 1a is also described.

Structure–activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues

Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-beta-carboline, showed the best in vitro activity, with an IC(50) value of 0.45 microM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI>1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure-activity relationships are discussed and compared with related naturally occurring compounds.

Synthesis of some diazino-fused tricyclic systems via Suzuki cross-coupling and regioselective nitrene insertion reactions

Suzuki coupling of 5-chloro-2-methyl-6-phenylpyridazin-3(2H)-one, 6-chloro-1,3-dimethyluracil and 2-chloropyrazine with protected aminoaryl boronic acids resulted in the corresponding pivaloylaminophenyl diazines which were transformed to diazino-fused indole and cinnoline derivatives. Suzuki coupling of 5-amino-6-chloro-1,3-dimethyluracil with 2-formylphenyl boronic acid afforded a novel pyrimidoisoquinoline ring system in a one-pot reaction.

Synthesis of new pyridazino[4,5-c]isoquinolinones by Suzuki cross-coupling reaction

Suzuki cross-coupling reaction of 2-alkyl(methyl and benzyl)-5-chloro-4-methoxy- and 2-alkyl(methyl and benzyl)-4-chloro-5-methoxypyridazin-3(2H)-ones with 2-formylphenylboronic acid afforded the corresponding biaryl products which were cyclized with ammonia to yield hitherto undescribed pyridazino[4,5-c]isoquinolinones. Removal of the N-benzyl protective group in position 2 yielded the unsubstituted tricyclic pyridazinones.

Synthesis of 4-aryl-5-hydroxy- and 5-aryl-4-hydroxypyridazin-3(2H)-ones and their use in the preparation of 4,5-diarylpyridazin-3(2H)-ones and hitherto unknown isochromeno[3,4-d]pyridazinediones

Abstract Easily accessible 2-substituted 4-aryl-5-methoxy- and 2-substituted 5-aryl-4-methoxypyridazin-3(2 H )-ones were transformed into the corresponding aryl-hydroxypyridazin-3(2 H )-ones by alkaline hydrolysis. The use of these compounds in the synthesis of 2-substituted 4,5-diarylpyridazin-3(2 H )-ones with two differently substituted aryl groups was investigated. Two aryl-hydroxypyridazin-3(2 H )-ones, 2-(2-benzyl-5-hydroxy-3-oxo-2,3-dihydropyridazin-4-yl)benzaldehyde and 2-(1-benzyl-5-hydroxy-6-oxo-1,6-dihydropyridazin-4-yl)benzaldehyde, were transformed into 2-benzyl-1 H -isochromeno[3,4- d ]pyridazine-1,6(2 H )-dione and 3-benzyl-3 H -isochromeno[3,4- d ]pyridazine-4,6-dione, respectively, via oxidation of the formyl group with KMnO 4 followed by lactonization.