EFFECT OF FLUORINE SUBSTITUTION OF ALPHA-HYDROGEN AND BETA-HYDROGEN ATOMS IN ETHYL PHENYLACETATE AND PHENYLPROPIONATE ON THEIR STEREOSELECTIVE HYDROLYSIS BY CULTURED CANCER-CELLS

(+/-)-Ethyl 2-fluoro-2-phenylacetate was stereoselectively hydrolyzed by cultured cells of several rat cancer cell lines to give the carboxy lic acid rich in the R enantiomer. The stereoselectivity increased for (+/-)ethyl 2-fluoro-2-phenylpropionate (2b) with all present cell lin es and for (+/-)-ethyl 2-phenyl-3,3,3-trifluoropropionate (3b) with ra t hepatoma McA-RH7777 cell line. The stereoselectivity was different f or the different cell lines, as McA-RH7777 cells preferred (R)-2b in c ontrast with the preference towards (S)-2b by other cells such as ras oncogene-transformed rat liver Anr4 cells, These stereoselectivities w ere different from those for non-fluorinated (+/-)ethyl 2-phenylpropio nate. Thus fluorine atoms are recognized by ester hydrolases of cancer cells, and fluorine substitution on the acyl group will be useful for making ester-type anticancer prodrugs more specific to cancer cells.