Multigram-scale enzymatic kinetic resolution of trans-2-azidocyclohexyl acetate and chiral reversed-phase HPLC analysis of trans-2-azidocyclohexanol

Abstract

Lipase-catalyzed hydrolytic kinetic resolution is a method of obtaining optically pure chiral alcohols and amines, which requires additional tools for determining enantiomerical purity. Herein, we present a study on multigram-scale hydrolytic kinetic resolution of trans-2-azidocyclohexyl acetate using Pseudomonas cepacia lipase immobilized on Immobead support. We investigated several parameters of the preparative-scale process: temperature, organic co-solvent, and the influence of calcium ions. Moreover, we have developed an efficient fluorenylmethyloxycarbonyl chloride (Fmoc-Cl) derivatization protocol for 2-azidocyclohexanol, which enabled chiral reversed-phase high-performance liquid chromatography (RP-HPLC) determination of enantiomeric excess.

Keywords: 2-azidocyclohexanol; Fmoc derivatization; Fmoc ester; chiral RP-HPLC; hydrolytic kinetic resolution; lipase.