Syntheses of 6-(2-hydroxy-6-phenylhexyl)-5,6-dihydro-2H-pyran-2-one derivatives and their cytotoxicities

Abstract

The cytotoxicities against cancer cells (HL-60, HeLa) and insect cells (Sf9) of four stereoisomers of 6-(2-hydroxy-6-phenylhexyl)− 5,6-dihydro-2 H -pyran-2-one ( 1 ) were evaluated, and then their structure-activity relationships examined. The 2′-dehydroxy derivative 5 of (6 R ,2′ R )- and (6 R ,2′ S )- 1 showed the highest activity against HeLa cells (IC 50 = 1.4 μM). To evaluate the effect of the 2′-hydroxy group of 1 , 6 R -and 6 S -oxetane derivatives were also synthesized and their activities examined. Against HeLa and HL-60 cells, the activities of the less potent stereoisomers were enhanced 3–4-fold by the introduction of the oxetane moieties at the 2′-position. Against the insect cell line (Sf9), phenyl derivative 7 showed the highest activity with an IC 50 value of 8.0 μM. • The cytotoxicities of all stereoisomers of 6-(2-hydroxy-6-phenylhexyl)− 5,6-dihydro-2 H -pyran-2-one were evaluated. • Structure-cytotoxicity relationship of 6-(2-hydroxy-6-phenylhexyl)− 5,6-dihydro-2 H -pyran-2-one was examined. • The effects of stereochemistry, oxetane structure, and secondary hydroxy group were clarified. • The derivative without secondary hydroxy was most effective.