Highly diastereoselective synthesis of enantiopure naphthylaminoalcohols with analgesic properties

Abstract

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.

PEG 400/Cerium Ammonium Nitrate Combined with Microwave-Assisted Synthesis for Rapid Access to Beta-Amino Ketones. An Easy-to-Use Protocol for Discovering New Hit Compounds

“…According to data in the literature concerning the different reactivities of secondary amines related to their structures and experimental conditions in the Mannich reaction [ 25 , 35 ], we set up a novel protocol using the cyclic and acyclic amines a and b as “building block” models. First, compounds 1a and 1b were synthesized with conventional heating, applying an existing protocol ( Figure 4 , condition A), and were properly purified [ 36 ]. Molar extinction coefficients of acetophenones 1 , 1a , and 1b were determined (1.265 × 10 4 , 6.327 × 10 3 , and 6.703 × 10 3 L·mol −1 ·cm −1 , respectively) and high performance liquid chromatography-ultraviolet-photodiode array detector (HPLC-UV-PAD) methods were devecloped to determine the percentage of conversion and purity of new compounds.…”