Mohamed Lotfi Efrit

Synthesis and biological evaluation of new N-acyl-homoserine-lactone analogues, based on triazole and tetrazole scaffolds, acting as LuxR-dependent quorum sensing modulators

New analogues of N-acyl-homoserine-lactone (AHL), in which the amide was replaced by a triazole or tetrazole ring, were prepared and tested for their activity as LuxR-dependent QS modulators. Several compounds showed a level of antagonistic or agonistic activity, notably some 1,4-triazolic and 1,5-tetrazolic derivatives, whereas the 2,5-tetrazolic compounds were inactive. In 1,5-tetrazoles, substituted with butyrolactone and an alkyl chain, the activity was reversed, depending on the connection between the lactone and the tetrazole. The C-N connected compounds were agonists whereas the C-C connected ones were antagonists.

AHL-dependent quorum sensing inhibition: synthesis and biological evaluation of α-(N-alkyl-carboxamide)-γ-butyrolactones and α-(N-alkyl-sulfonamide)-γ-butyrolactones.

New N-acylhomoserine lactone (AHL) analogues in which the amide function is replaced by a reverse-amide one have been studied as AHL QS modulators. The series of compounds consists of α-(N-alkyl-carboxamide)-γ-butyrolactones, α-(N-alkyl-sulfonamide)-γ-butyrolactones, and 2-(N-alkyl-carboxamide)-cyclopentanones and cyclopentanols. Most active compounds exhibited antagonist activities against LuxR reaching the 30 μM range.

Reactivite Des α -Phosphonylketones Dans la Reaction de Gewald: Synthese de Nouveaux Derives de L′aminophosphonothiophene

The reaction of α -phosphonylketones 1 with active methylenenitriles 2 leads to phosphonoalkylidenes 3 . The reaction of compounds 3 with sulfur under basic conditions leads to the new 2-amino-4-phosphonothiophenes 4 . The structure of all obtained products was confirmed by NMR (1H, 31P, 13C) and IR spectroscopy, and in some cases by mass spectrometry.

Les α et β-Cetophosphonates, des Precurseurs de Pyrrolidines et de Quinoleines Phosphonatees

The condensation of primary amines on α- or β-ketophosphonates affords the corresponding iminophosphonates. The reaction was found to be highly stereoselective, affording the E isomer exclusively. These phosphonylimines were then treated in basic media to give pyrrolidines and quinolines through intramolecular cyclization. The structures of all obtained products were confirmed by NMR spectroscopy (1H, 31P, 13C), and in some cases by mass spectrometry.

ACTION DU REACTIF DE LAWESSON SUR LES HYDRAZONATES ET LES HYDROXYMATES: SYNTHESE DE SULFURES DE 1,3,4,2-THIADIAZAPHOSPHOLINES ET DE SULFURES DE 1,3,5,2-OXATHIAZAPHOSPHOLINES

Abstract The Lawesson Reagent (L.R) 1 reacts with hydrazonates 2 and hydroxymates 3 to give 1,3,4,2-thiadiazaphospholines 4 and 1,3,5,2-oxathiazaphospholines 5 derivatives. The structure of products 4 and 5 is confirmed by IR and NMR spectroscopy.

γ-Alkylsulfide phosphonates through the thia-Michael strategy

The formation of γ-alkylsulfide phosphonates is described from allylphosphonates under mild conditions using thiols through the thia-Michael strategy. A series of new phosphonates, bisphosphonates were cleanly prepared in high yields. The methodology developed allowed further preparing γ-alkylsulfide phosphonates bearing valuable esters groups in β and δ positions with respect to the phosphonate moiety. GRAPHICAL ABSTRACT

Theoretical investigations on the mechanistic pathway of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines.

The mechanism of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines 1 has been studied using quantum chemistry methods. Geometries of reactants, transition states and products have been optimized at the B3LYP/6-311++G(2d,2p) level. Relative energies for various stationary points have been determined and reaction identified by IRC calculations. The results show that thermal rearrangements occur in three ways. Firstly, the transition state TS1 in which a hydrogen atom of methyl groups migrates from primary carbon to oxygen of amid group to give the N-methallylamide 2. The second is via the transition state TS2 in which the attack of oxygen to the tertiary carbon yields the oxazoline 3. The third is via the transition state TS3 in which a hydrogen migrate from the secondary carbon to oxygen to give the vinylamide 4. In order to get insights into the factors determining the exact nature of its interactions with electrophiles, the application of reactivity parameters derived from density functional theory in a local sense, in particular the softness and Fukui function, to interpret and predict the mechanisms of the thermal decomposition of the N-acyl-2,2-dimethylaziridines 1, has been discussed.

Isomerisation Catalysee Par le Gel de Silice et L'argile Activee de N-Acyl-2,2-Dimethylaziridines: Approche Mecanistique

Silica gel and activated clay, behaving as Lewis acids, reacted with N-acyl-2,2-dimethylaziridines 1 to lead to pentacoordinated aziridinium silicate ions. The regiospecific ring opening on the CMe2 carbon side of the intermediate I involves, after removal of the catalyst, the zwitterion II. The zwitterion II undergoes either a transfer of proton leading to the N-methallylamide 2 or intramolecular cyclization reaction leading to the oxazoline 3. The unstable oxazoline 3 on catalyst is hydrated in turn into amidoalcohol 4 via the oxazolinium silicate III.

Convenient Synthesis of 2,4-Disubstituted Tetrahydrothiophenes from Mannich's Adducts

Abstract Ammonium salts of β-functionalized allylic amines 1 were successfully employed as electrophilic agents with functional thiols. The obtained intermediate 2 underwent intramolecular cyclization in the presence of potassium tert-butoxide to afford 2,4-disubstituted tetrahydrothiophenes 3.

From α-Bromomethylbutenolide to Fused Tri(Tetra) Cyclic Dihydrofurandiones through Barbier Reaction–Heck Arylation Sequence

A Barbier reaction–Heck arylation sequence from α-bromomethylbutenolide to fused tri and tetracyclic lactones has been developed. The first step involving a Barbier reaction enabled installing ortho-bromoaromatics in α-ylidene γ-lactones. The latter substrates were subjected to intramolecular Heck reaction conditions which selectively afforded 6,5,5 or 6,6,5 fused ring systems depending on the nature of the base employed.