Potential carcinostatics. Synthesis and biological properties of d- and 1-beta,beta-difluoroaspartic acid and beta,beta-difluoroasparagine.

Di-tert-butyl beta,beta-difluorooxaloacetate, prepared by fluorination of di-tert-butyl oxaloacetate with perchloryl fluoride, was converted to di-tert-butyl beta,beta-difluoroaspartate via its O-methyl oxime, followed by reduction. The tert-butyl ester was hydrolyzed to give a mixture of dl-beta,beta-difluoroaspartic acid, which was resolved via its brucine salts. dl-Difluoroaspartic acid was converted into beta,beta-difluoroasparagine by monoesterification and subsequent ammonolysis. Racemic beta,beta-difluoroaspartic acid inhibits aspartate aminotransferase. Cell growth of 3T3-F cells was slightly inhibited by l-beta,beta-difluoraspartic acid while the d enantiomer was without effect in this test system.