Tommy J. McCord

THE SYNTHESIS AND BIOLOGICAL ACTIVITIES OF SOME AZA ANALOGS OF AMINO ACIDS. I. 4-AZALEUCINE, AN INHIBITORY ANALOG OF LEUCINE.

Abstract 4-Azaleucine (2-amino-3-dimethylaminopropionic acid) was prepared by condensing 2-acetamidoacrylic acid and dimethylamine, followed by hydrolysis of the resulting intermediate condensation product. 4-Azaleucine is a potent growth inhibitor for Escherichia coli 9723 and is moderately toxic for Leuconostoc dextranicum 8086. The growth toxicities in both organisms were competitively reversed by leucine.

The syntheses and biological activities of o-aminophenylalanine and related compounds.

Abstract o -Nitrophenylalanine was prepared by the acid hydrolysis of the condensation product resulting from the interaction of o -nitrobenzyl chloride with ethyl acetamidomalonate in the presence of sodium ethylate and subsequently hydrogenated to yield o -aminophenylalanine. Catalytic hydrogenation of ethyl 2-acetamido-2-( o -nitrobenzyl)malonate, followed by acid hydrolysis, yielded 3-aminohydrocarbostyril instead of o -aminophenylalanine. The latter compound in acidic medium readily cyclizes to form 3-aminohydrocarbostyril. Growth inhibition of Escherichia coli 9723 by o -aminophenylalanine is reversed in a competitive manner by phenylalanine over a 100-fold range of increasing concentrations with an inhibition index of 300–1000, whereas the toxicity of 3-aminohydrocarbostyril is not reversed by phenylalanine in a competitive manner.

2,6-Diamino-4-hexynoic acid, a lysine analog

The reaction of 1,4-dichloro-2-butyne with potassium phthalimide yielded N -(4-chloro-2-butynyl)phthalimide, which was subsequently condensed with ethyl acetamidomalonate. Acid hydrolysis of the condensation product gave 2,6-diamino-4-hexynoic acid. Growth inhibition of Leuconostoc dextranicum 8086 by 2,6-diamino-4-hexynoic acid is reversed in a competitive manner by lysine over a hundredfold range of increasing concentrations with an inhibition index of about 10.