Application of Green Chiral Chromatography in Enantioseparation of Newly Synthesized Racemic Marinoepoxides.

Enantioseparation of the newly synthesized series of novel quinoline-2(1 H )-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(1 H )-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 CO 2 /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.