The identification of novel pan-Sigma Receptor (SR) modulators, potentially useful in cancer treatment, represents a new goal of our research. Here we report on the preparation of novel chiral compounds characterized by a 3-C alkyl chain bridging an aromatic portion to a 4-benzyl-piperidine moiety. All the studied compounds have been prepared both in racemic and enantiomerically pure form, with the final aim to address the role of chirality in the SR interaction. To isolate and characterize enantiomeric compounds, high-performance liquid chromatography (HPLC) procedures were set up. A systematic analytical screening, involving several combination of chiral stationary and mobile phases, allowed us to optimize the analytical resolution and to set up the (semi)-preparative chromatographic conditions. Applying the optimized procedure, enantiomeric resolution of the studied compounds was successfully achieved, obtaining all the compounds with an enantiomeric excess higher than 95. Lastly, the absolute configuration has been empirically assigned to enantiopure compounds, combining the electronic circular dichroism (ECD) technique to the elution order study
Novel enantiopure sigma receptor modulators: Quick (semi-)preparative chiral resolution via hplc and absolute configuration assignment
RUI, MARTA;MARRA, ANNAMARIA;ROSSI, DANIELA;COLLINA, SIMONA
2016-01-01
Abstract
The identification of novel pan-Sigma Receptor (SR) modulators, potentially useful in cancer treatment, represents a new goal of our research. Here we report on the preparation of novel chiral compounds characterized by a 3-C alkyl chain bridging an aromatic portion to a 4-benzyl-piperidine moiety. All the studied compounds have been prepared both in racemic and enantiomerically pure form, with the final aim to address the role of chirality in the SR interaction. To isolate and characterize enantiomeric compounds, high-performance liquid chromatography (HPLC) procedures were set up. A systematic analytical screening, involving several combination of chiral stationary and mobile phases, allowed us to optimize the analytical resolution and to set up the (semi)-preparative chromatographic conditions. Applying the optimized procedure, enantiomeric resolution of the studied compounds was successfully achieved, obtaining all the compounds with an enantiomeric excess higher than 95. Lastly, the absolute configuration has been empirically assigned to enantiopure compounds, combining the electronic circular dichroism (ECD) technique to the elution order studyI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
