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.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001216:Asparagine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000503:physiopathology; D051379:Mice; D051381:Rats; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D001224:Aspartic Acid; D001216:Asparagine; D001219:Aspartate Aminotransferases