Potential carcinostatics. 4. Synthesis and biological properties of erythro- and threo-beta-fluoroaspartic acid and erythro-beta-fluoroasparagine.
(E)- and (Z)-Di-tert-butyl 2-amino-3-fluoro-2-butene-1,4-dioate [(E)- and (Z)-2] were synthesized in two ways: (a) 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 (b) 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 L-5178Y test system showed that the compounds exhibited toxicity at levels at which no antitumor activity was observed.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001216:Asparagine / Q000031:analogs & derivatives*; D001224:Aspartic Acid / Q000031:analogs & derivatives; D005260:Female; D007940:Leukemia L5178 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009374:Neoplasms, Experimental / Q000188:drug therapy
D000970:Antineoplastic Agents; D001224:Aspartic Acid; C023463:beta-fluoroaspartic acid; D001216:Asparagine; C023464:beta-fluoroasparagine