Enantioselective Synthesis and Cytotoxic Evaluation of 4,5-Dihydro-5-[aryl(hydroxy)methyl]-3-methylidenefuran-2(3H)-ones

A series of enantiomerically enriched 4,5‐dihydro‐5‐[aryl(hydroxy)methyl]‐3‐methylidenefuran‐2(3H)‐ones (8) were synthesized by means of asymmetric Sharpless dihydroxylation of the 2‐phosphorylated 5‐aryl‐pent‐4‐enoic acids 13, followed by Horner–Wadsworth–Emmons reaction of the resulting furanones 15 (Scheme 2). An enantiomeric excess (ee) of 20–95% was achieved for compounds 8, and their absolute configurations were determined by the Mosher ester method. Cytotoxic evaluation against L‐1210 and HL‐60 leukemia cell lines revealed that the target compounds 8 are active in the micromolar concentration range (Table 2). Thereby, significant differences in activity between the corresponding enantiomers were observed for the HL‐60 cell line.