Laboratory-Scale Semipreparative Enantioresolution of Phenylethanolic-Azole Heme Oxygenase-1 Inhibitors

In the present work, the development and application of two HPLC methods enabling the semipreparative enantioresolution of 1-(biphenyl-3-yl)-2-(1H-imidazol-1-yl)ethanol (1) and 1-[4-[(4-bromobenzyl)oxy]phenyl]-2-(1H-imidazol-1-yl)ethanol (2), two among the most potent and selective heme oxygenase-1 (HO-1) inhibitors known, are described. During the optimization step, different chiral stationary phase (CSP) features were evaluated, especially focusing the attention on (1) the type (electron-donating and electron-withdrawing) and position of the substituents in the phenyl moiety; (2) the physical coating or covalent immobilization of the modified polymer chain. Additionally, the effect of different types and amount of alcohol in the normal-phase eluent as well as of the column temperature, were investigated. For compound 1, Lux Cellulose-1 CSP containing cellulose tris(3,5-dimethylphenylcarbamate) was identified as the optimal choice in combination with a mobile phase consisting of n-hexane/ethanol—85/15 (v/v). Conversely, for compound 2, Lux Cellulose-2 CSP containing the cellulose tris(3-chloro-4-methyl phenylcarbamate)-based chiral selector was identified as the optimal choice, running the analysis with a n-hexane/ethanol/2-propanol—80/15/5 (v/v/v) mobile phase.