Short malonyl dehydro peptides as potential scaffolds for peptidomimetics by an efficient Knoevenagel reaction.

Non-symmetric disubstituted malonamides rAA-mGly-AA', obtained from Meldrum's acid, were considered as methylene active compounds and a Knoevenagel condensation methodology was developed involving piperidine and activated 4 A molecular sieves as catalysts. The reaction is efficient, broad in scope, and easy to perform and allows access to E/Z mixtures of short malonyl dehydro peptides (MDHPs) rAA-m Delta(2)AA''-AA', partially modified retro peptides characterized by an interesting combination of retro and dehydro modifications in the same structure.

An unexpected highly stereoselective bisaziridination of (E,E)-1,4-dialkyl-2,3-dinitrobutadienes followed by a nitro group driven ring enlargement.

(+/-)-2,2'-Dinitro-2,2'-biaziridines were obtained by a direct aza-MIRC (Michael initiated ring closure) reaction on (E,E)-1,4-dialkyl-2,3-dinitro-l,3-butadienes under very mild conditions. The reactions occur with high stereoselectivity as shown by the enantioselective HPLC analyses performed on the crude mixtures. Ring enlargement to 3,3'-bi(1,2,4-oxadiazole) derivatives was easily obtained by a simple treatment with sodium iodide in DMSO, with an unforeseen regioselective aziridine C-C cleavage.

Solution-phase synthesis of 2-cyano and 2-amido aziridinyl peptides.

Starting from a library of 2-l-α-amino acyl ()-acrylonitriles, different short 2-cyano and 2-amido aziridinyl peptides, potential protease inhibitors, were obtained under parallel solution-phase conditions. The transformations include careful selection of conditions for aziridine deprotection and cyano group partial hydrolysis.

Facile and highly stereoselective one-pot synthesis of either (E)- or (Z)-nitro alkenes.

Aliphatic aldehydes were reacted with nitro alkanes in the presence of catalytic amounts of piperidine over 4 A molecular sieves. Simply by changing reaction conditions (solvent and temperature) it is possible to control the stereochemical outcome of the reactions, obtaining pure (E)- and (Z)-nitro alkenes in high to excellent yields. The role of molecular sieves on the stereochemical control seems crucial in addition to that of piperidine, especially for the synthesis of the Z isomer.

Parallel solution-phase synthesis of acrylonitrile scaffolds carrying L-alpha-amino acidic or D-glycosyl residues.

A practical and straightforward protocol for the preparation of a solution-phase library of acrylonitrile scaffolds is reported. Target compounds were obtained in high yield, stereoselectivity, and purity by two simple and practical steps from cyanoacetic acid. Moreover, our study proposes a synthetic approach starting from the constructed library to obtain three-membered heterocycles.

Amination of CF3-enones with nosyloxycarbamates.

CF3-enones showed a different reactivity in amination reactions with nosyloxycarbamates. 4-Oxazolines or vinyl carbamates were obtained as unique products depending on the nature of double-bond substituents and on the choice of carbamates and bases. Starting from trans-trifluoroacetyl olefins carrying a heterocyclic residue or the p-methoxyphenyl group on the double bond, a rare loss of CF3CO was observed when the aminations were performed under heterogeneous conditions using CaO as the base.

Unexpected and expeditious entry into trifluoromethyl aziridines from substituted beta-dicarbonyl compounds.

[Reaction: see text]. One-pot aziridinations were obtained starting from substituted 2,2,2-trifluoroethyl beta-dicarbonyl compounds with nosyloxycarbamates in the presence of an excess of CaO as base. The unexpected ring closure reaction takes place at room temperature, leading to the N-protected alpha-trifluoromethyl aziridines with good yields.

Aziridines versus vinyl carbamates from the direct amination of electron-withdrawing group-substituted trifluoromethyl enoates.

Aza-MIRC (Michael-initiated ring closure) and C-H insertion products were obtained in the reactions of trifluoromethylated olefins with different nosyloxycarbamates by changing base and solvent. Aza-Michael addition products were not isolated. The presence and the position of the trifluoromethyl group allow control of the outcome of the reactions.

Functionalised enones as starting materials for the construction of aziridine scaffolds.

alpha-Substituted beta-keto esters have been transformed by means of a straightforward procedure into aziridine-1,2-dicarboxylates, which have been efficiently converted into alkenyl aziridine-1,2-dicarboxylates through Wittig olefination reaction. The possibility of aziridine ring elaborations and the presence of an olefin function make these new molecules suitable scaffolds for further derivatisation into potential bioactive targets.

Aza-Michael addition of nosyloxycarbamates to 2-(trifluoromethyl)acrylates.

[reaction: see text] The amination of 2-(trifluoromethyl)acrylates, performed by nosyloxycarbamates, gives two different aminated products, the derivatives of alpha-trifluoromethyl beta-amino esters or the aziridines, in high yields by changing the reaction conditions. The aza-Michael addition product was isolated for the first time in this kind of reaction. This finding confirms the aza-MIRC mechanism we previously proposed.

One-pot synthesis of polyfunctionalized cyclic urea derivatives.

[reaction: see text] Unexpectedly, imidazolidin-2-ones are easily obtained from beta-keto esters upon treatment with tert-butyl nosyloxycarbamate and calcium oxide under mild conditions. The structure of the product was established by X-ray crystallography.

Diastereoselective aziridination of chiral alpha-carbonyl enoates.

Nosyloxycarbamates very efficiently aziridinate optically active alpha-carbonyl enoates with high levels of diastereoselectivity under mild conditions and in a straightforward process.