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The enantiomers of aromatic 4-dibenzocyclooctynol (DIBO), used for radiolabeling and subsequent conjugation of biomolecules to form radioligands for positron emission tomography (PET), were separated by kinetic resolution using lipase A from <i>Candida antarctica</i> (CAL-A). In optimized conditions, (<i>R</i>)-DIBO [(<i>R</i>)-<b>1</b>, ee 95%] and its acetylated (<i>S</i>)-ester [(<i>S</i>)-<b>2</b>, ee 96%] were isolated. In silico docking results explained the ability of CAL-A to differentiate the enantiomers of DIBO and to accommodate various acyl donors. Anhydrous MgCl₂ was used for binding water from the reaction medium and, thus, for obtaining higher conversion by preventing hydrolysis of the product (<i>S</i>)-<b>2</b> into the starting material. Since the presence of hydrated MgCl₂&#183;6H₂O also allowed high conversion or effect on enantioselectivity, Mg²⁺ ion was suspected to interact with the enzyme. Binding site predictions indicated at least two sites of interest; one in the lid domain at the bottom of the acyl binding pocket and another at the interface of the hydrolase and flap domains, just above the active site.