Potential carcinostatics. 4. Synthesis and biological properties of erythro- and threo-.beta.-fluoroaspartic acid and erythro-.beta.-fluoroasparagine

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Abstract
(E)- and (Z)-Di-tert-butyl 2-amino-3-fluoro-2-butene-1,4-dioate [(E)- and (Z)-2] were synthesized in the following 2 ways: by elimination of hydrogen fluoride from di-tert-butyl .beta.,.beta.-difluoroaspartate under the influence of 1,5-diazabicyclo[4.3.0]non-5-ene, and by amination with the ammonium acetate of di-tert-butyl monofluorooxaloacetate (3) obtained via condensation of tert-butyl monofluoroacetate with di-tert-butyl oxalate. Reduction of 2 with sodium cyanoborohydride yielded a mixture of di-tert-butyl monofluoroaspartates in which the erythro isomer constituted the major product. The structure of this isomer (4a) was established by X-ray crystallographic analysis of the corresponding acid 5a. Esterification of 5a to the .beta.-methyl ester 6 followed by aminolysis yielded erythro-.beta.-fluoroasparagine (7). Tests with 5a and 7 in the [mouse leukemia] L-5178Y test system showed that the compounds exhibited toxicity at levels at which no antitumor activity was observed.