Enantioseparation of the newly synthesized series of novel quinoline-2(1H)-one epoxide structures rac-6a-c and rac-8a-c, named marinoepoxides, is described. Marinoepoxide rac-6a, the key intermediate in the total synthesis of natural products marinoaziridines A and B, as well as their structural analogues, was synthesized by addition of the achiral ylide generated in situ from the sulfonium salt 5 or 7, to the carbon-oxygen double bond of the corresponding quinoline-2(1H)-one-4-carbaldehyde 4a-c in good yield. Separation of enantiomers of (±)-2,3,3-trisubstituted marinoepoxides rac-6a-c and (±)-trans-2,3-disubstituted marinoepoxides rac-8a-c was studied using two immobilized polysaccharide type chiral stationary phases (CSPs); tris-(3,5-dichlorophenylcarbamoyl)cellulose stationary phase (CHIRAL ART Cellulose-SC) and tris-(3,5-dimethylphenylcarbamoyl)amylose stationary phase (CHIRAL ART Amylose-SA). Enantioseparation conditions were explored by high-performance liquid chromatography (HPLC) using dimethyl carbonate/alcohol mixtures and n-hexane/ethanol (80/20, v/v) as mobile phase, and by supercritical fluid chromatography (SFC) using CO2/alcohol mixtures as mobile phase. In all examined racemates, enantioseparation was successfully achieved, but its efficiency largely depended on the structure of chiral selector and type/composition of the mobile phase.
Keywords: 2,3,3-trisubstituted epoxides; 2,3-disubstituted epoxides; chiral chromatography; dimethyl carbonate (DMC); enantioseparation; green solvents; high-performance liquid chromatography (HPLC); marinoaziridines; marinoepoxides; supercritical carbon dioxide; supercritical fluid chromatography (SFC).