Carme Masdeu

Formation of γ-oxoacids and 1H-pyrrol-2(5H)-ones from α,β-unsaturated ketones and ethyl nitroacetate.

Michael addition of ethyl nitroacetate on α,β-unsaturated ketones followed by Nef oxidation under hydrolytic conditions yields γ-oxoacids instead of the corresponding α,δ-dioxoesters. A concerted decarboxylation step is proposed on the basis of computational results. Finally, conversion of the γ-ketoacids thus prepared into 1H-pyrrol-2(5H)-ones by reaction with primary amines under Paal-Knorr conditions is also reported.

AZOLE ADDITIONS UPON AZINIUM SALTS

Abstract The additions of pyrrole and indole upon N -acetyl- and N -alkylpyridinium, quinolinium or isoquinolinium salts are reported. The resulting dihydroazines are either isolated or oxidised to the more stable aromatic compounds. The use of a two-phase system was studied and slight enantiomeric excesses were observed when chiral catalysts were used. The separation of enantiomers of some 4-indolyl-1,4-dihydropyridines was achieved by HPLC using chiral stationary phases.

Benzimidazolium Salts as Small, Nonpeptidic and BBB-Permeable Human Prolyl Oligopeptidase Inhibitors

Prolyl oligopeptidase (POP) is a cytosolic serine peptidase that hydrolyzes proline‐containing peptides at the carboxy terminus of proline residues. This peptidase has gained importance as a target for the treatment of cognitive disturbances of patients with neuropsychiatric diseases. Our research addresses the identification of POP inhibitors from a small focused library of polar heterocyclic compounds arising from multicomponent reactions. Two selective POP‐specific inhibitors were identified on the basis of their inhibition of dipeptidyl peptidase IV. The most active compounds were evaluated for their in vitro transport through the blood–brain barrier (BBB) using a parallel artificial membrane permeability assay. Our results show for the first time that benzimidazolium salts are new POP‐inhibitory scaffolds with properties of solubility, specificity, and lipophilicity that may allow them to cross the BBB by passive diffusion. These findings constitute an excellent starting point to synthesize new POP inhibitors with enhanced properties.

Vicinal diamination of 1,4-dihydropyridines

Electrophilic interaction of iodine with N-alkyl-1,4-dihydropyridines 1 in the presence of secondary amines stereoselectively leads to the corresponding trans-2,3-diamino-1,2,3,4-tetrahydropyridines 2 in satisfactory yields (79–94%); the method allows the synthesis of piperidine, pyrrolidine, morpholine and piperazine derivatives.