Improving the kinetic resolution of rac-2-(diphenylthiophosphinoferrocene) methanol catalyzed by Thermomyces lanuginosus lipase immobilized on immobead-150

Abstract

The organometallic 2-(diphenylthiophosphinoferrocene)methanol (1) is a ferrocene derivative that exhibits planar chirality. In this work, we report the lipase mediated kinetic resolution (KR) of rac-1, via acylation reaction, as a more sustainable alternative to produce the chiral compounds. The study resulted the enantiopure remaining alcohol (Rp)-1 (ees = >99%) and its enantioenriched acetate (Sp)-2 (eep = 98%) with ideal conversion (c = 50%) and enantioselectivity (E > 200) values when the KR was catalyzed by the lipase from Thermomyces lanuginosus immobilized on immobead-150 (enzyme:substrate ratio 1:1 (w/w); vinyl acetate as acylating agent; toluene as solvent; 35°C; 48 h). Results from molecular docking study confirmed the enantiopreference of the lipase for acetylating the (Sp)-alcohol, yielding (Sp)-2 as product. Additionally, the cytotoxicity of rac-1 and its enantiomer (Rp)-1 was investigated against SNB-19 (Astrocytoma), HCT-116 (Human Colon Carcinoma), PC3 (Prostate Carcinoma), HL60 (Promyelocytic Leukemia), and non-tumor HACAT (Human keratinocytes) cell lines. Both compounds showed very low cytotoxicity and no selectivity.