Faïza Diaba

Synthesis and structure–activity relationships of γ-carboline derivatives as potent and selective cysLT1 antagonists

A gamma-carboline series of cysLT(1) receptor antagonists has been prepared. Some of the compounds show good potencies both, in vitro and in vivo, compared to the standard compounds.

Synthesis of the tetracyclic ABCD ring systems of madangamines D-F.

Synthesis of the tetracyclic cores of madangamines D-F was achieved, featuring a reductive radical process from an ethoxycarbonyldichloroacetamide to build the morphan nucleus, a Mitsunobu-type aminocyclization toward the common diazatricyclic intermediate, and ring-closing metathesis reactions for the macrocyclization step leading to the 13- to 15-membered rings.

NMR evidence of the kinetic and thermodynamic products in the NIS promoted cyclization of 1-phenyl-4-pentenylamines. Synthesis and reactivity of trans-2-phenyl-5-iodopiperidines

The intramolecular reaction of secondary amines with tethered alkenes using NIS was studied, which gave insight into the kinetic vs. thermodynamic control of the iodoaminocyclization and the regioselectivity of the aziridinium ring-opening reactions, and led to functionalized piperidines.

Translocation versus cyclisation in radicals derived from N-3-alkenyl trichloroacetamides

Under radical reaction conditions, two different and competitive reaction pathways were observed for N-(α-methylbenzyl)trichloroacetamides with a N-3-cyclohexenyl substituent: 1,4-hydrogen translocation and radical addition to a double bond. However, for radicals with an acyclic alkenyl side chain, the direct cyclisation process was exclusively observed. The dichotomy between translocation and direct radical cyclisation in these substrates has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6-31G** computational level.

Synthesis of immunosuppressant FR901483 and biogenetically related TAN1251 alkaloids

Abstract The review covers the synthetic studies of FR901483 and the biogenetically related TAN1251 alkaloids.

Intramolecular radical non-reductive alkylation of ketones via transient enamines

Radical cyclization of dichloroacetamide-tethered ketones using pyrrolidine, AIBN and TTMSS under microwave activation gave 2-azabicyclo[3.3.1]nonan-3,6-diones. In a five-minute one-pot process, after the generation of an enamine, intramolecular addition of a carbamoylchloromethyl radical, and oxidation of the α-aminoalkyl radical intermediate, the resulting iminium salt evolved to the corresponding enamine and, after a workup, to the alkylated ketone.

An unexpected course in the 6-exo radical cyclizations of trichloroacetamides on changing the N-substituent from benzyl to α-methylbenzyl

Abstract Radical cyclization of N-(α-methyl)benzyl substituted trichloroacetamides upon α,β-unsaturated nitriles has been studied. Tributyltin hydride treatment of trichloroacetamides 5a and 5b gives morphan derivatives (1 and 2), through a 6-exo-trig radical cyclization, and unexpectedly normorphans 6 and 7 as a result of a stereoespecific process in which the stereogenic benzylic carbon undergoes a configurational inversion.

Radical promoted cyclisations of trichloroacetamides with silyl enol ethers and enol acetates: the role of the hydride reagent [tris(trimethylsilyl)silane vs. tributylstannane]

Reactions between 1-(carbamoyl)dichloromethyl radicals and electron-rich alkenes acting as radical acceptors are reported for the first time. The intramolecular reaction of trichloroacetamides with silyl enol ethers gives ketones using (TMS)3SiH as the mediator, and alcohols when using Bu3SnH. The reaction with enol acetates gives acetates using either of the above hydride reagents. These radical processes have been applied to the synthesis of 2-azabicyclo[3.3.1]nonanes.

Synthesis of Normorphans through an Efficient Intramolecular Carbamoylation of Ketones

An unexpected C-C bond cleavage was observed in trichloroacetamide-tethered ketones under amine treatment and exploited to develop a new synthesis of normophans from 4-amidocyclohexanones. The reaction involves an unprecedented intramolecular haloform-type reaction of trichloroacetamides promoted by enamines (generated in situ from ketones) as counter-reagents. The methodology was applied to the synthesis of compounds embodying the 6-azabicyclo[3.2.1]octane framework.

Synthesis of substituted γ- and δ-lactams based on titanocene(III)-catalysed radical cyclisations of trichloroacetamides

A new procedure for the synthesis of γ- and δ-lactams based on a Cp2TiCl-catalysed cyclisation of trichloroacetamides under mild reaction conditions is reported. Theoretical studies supported the observed regioselectivity in the cyclisations and the mechanism involved in the dehalogenation process.