The diastereoselective synthesis via Grignard reaction of enantiopure analgesic naphthylaminoalcohols has been performed. The chiral racemic key intermediate 3-dimethylamino-2-methyl-1-(naphthalen-2-yl)propan-1-one and enantiomers were prepared and transformed into the desired compounds by addition of the organometallic reagent. The chemical characterization of all diastereoisomers was accomplished by 1H NMR and HPLC analyses and the absolute configuration assigned by CD spectroscopy. The in vitro and in vivo profile has also been evaluated.

We describe an easy and convenient procedure for palladium-catalyzed Heck arylation of disubstituted olefins via microwave irradiation. This method of synthesis produces trisubstituted olefins under phosphane-free conditions and in very short times.

We describe the preparation of racemic N,N-dimethyl-3-(naphthalen-2-yl)-butan-1-amines, potential sigma1 ligands, and their resolution via chiral HPLC. In order to obtain enantiopure compounds, direct chromatographic methods of separation using chiral stationary phases were investigated. Different methods suitable for both analytical and semipreparative purposes are proposed. The best resolutions were achieved using cellulose tris (3,5-dimethylphenyl carbamate) (Chiralcel OD and OD-H) and amylose tris (3,5-dimethylphenyl carbamate) (Chiralpak AD). On the basis of the preliminary chromatographic results, the resolution of compound 1 was transferred onto a Chiralcel OD semipreparative column. The enantiomers were obtained in high enantiomeric excess. The configurational assignment was performed by circular dichroism. Computational analysis was used to explore the enantioselective recognition process of compound 1 with the Chiralcel OD stationary phase.

A new, high yield regioselective reaction affording racemic and enantiomeric 1,2-dimethyl-3-[2-(6-substituted naphthyl)]-2H,5H-pyrrolines is reported. Compounds were provided by dehydration of the corresponding 1,2-dimethyl-3-[2-(6-substituted naphthyl)]-3-hydroxy-pyrrolidines under microwave irradiation and solvent-free conditions. Pharmacological properties of enantiomeric compounds are also described; the analgesic activity was investigated by the hot plate test. A conformational analysis of the compounds was carried out by molecular modeling techniques with the aim to get information about the fitting to known analgesic pharmacophore models.

The preparation and biological evaluation of a new class of arylpyrrolidinols is reported. The antinociceptive activity was evaluated in vivo with the hot plate test (HPT) and formalin test (FT), excluding any involvement on motor coordination with the rota-rod test (RRT). The nociceptive behavior in the late phase of FT (representative of chronic pain) suggests an involvement of the antiinflammatory process and it is clearly influenced by the stereochemical features, being the eutomer of phenylpyrrolidinols, the (2R,3S) enantiomer. Despite this, a specific mechanism of action is not yet clarified.

The diastereoselective synthesis of chiral nonracemic naphthylaininoalcohols has been accomplished. The diastereoisomers, obtained in high enantiomeric excesses, were investigated by H-1 NMR and HPLC analyses. The configurational assignment was performed by NOESY H-1 NMR spectroscopy. Pharmacological evaluation of the analgesic activity by means of the hot plate test is described. (C) 2004 Elsevier Ltd. All rights reserved.