Abstract

The enantiomers of 9-hydroxyrisperidone, the major metabolite of risperidone and the active component of the antipsychotic drug Invega^®, were synthesized by efficient methods. Their optical rotation and enantiomeric purity were characterized for the first time. The absolute configurations were assigned by comparing ¹H NMR chemical shifts of Mosher esters of a key stereoisomeric intermediate. Thus, the stereoisomeric center of (+)-9-hydroxyrisperidone has been assigned as the S configuration, and its enantiomer has the configuration R.

Keywords: Invega^®, 9-hydroxyrisperidone enantiomers, chiral HPLC, absolute configuration, synthesis.

Graphical Abstract