The Preparation and Reactions of N-Carboxyphenylhydrazidoamino Acids¹

Abstract

N-Carboxyphenylhydrazido derivatives of glycine, DL-alanine, DL-phenylalanine, DL-leucine, and DL-tyrosine have been prepared by refluxing carboalkoxyamino acid phenylhydrazides with potassium hydroxide in ethanol. The 5-substituted 3-anilinohydantoins were isolated as intermediates in the above reactions. The N-carboxyphenylhydrazidoamino acids were oxidized with potassium permanganate to give N-phenylazocarbonyl derivatives of the amino acids. The N-carboxyphenylhydrazido-DL-amino acids were used as substrates in a papain-catalyzed reaction with phenylhydrazine to give N-carboxyphenylhydrazido-L-amino acid phenylhydrazides.added. This solution -was refluxed, for 4 hr., and then cooled, and the salt was separated by filtration and washed with hot methanol; the yield was 11.3 g. (65%), m.p. 212-214°.

Multistep deprotection for peptide chemistry

“…The phenylhydrazide group was introduced by Milne & Kilday (19) as an effective amino acid carboxyl protecting group, being stable to a mild acid or base. After oxidation of the phenylhydrazide moiety with N-bromosuccinimide, the phenyldiimides are capable of peptide coupling.…”

Peptides containing dipropylglycine

“…Two-stage deprotection t o Tfa-Dpg was found t o be unnecessary; treatment with bromine in acetonitrile gave the carboxylic acid directly, despite the fact that the di-imide intermediate (14) normally formed in oxidative removal of hydrazides cannot be formed unless a t least one of the benzyl groups is removed. The presence of water was found t o be essential for the reaction, and three equivalents of bromine are consumed.…”

3‐Hydroxyhydantoine: Eine neue Klasse cyclisch diacylierter Hydroxylamine

“…5,s-dialkylierte Hydantoine liefern beim Kochen mit Hydrazinhydrat 5,5-dialkylierte 3-Aminohydantoine (Davidson [18]), wahrend aus Hydantoin selbst unter Ringoffnung nur Ureido-essigsaurehydrazid entsteht ([Z], S. 67). Die Cyclisierung von ~thoxycarbonylaminosaurephenylhydraziden zu 3-Anilinohydantoinen geht beim Glycinderivat am schlechtesten (Milne [19]).…”