A preparative method for the synthesis of N-aryl- and pyridine-substituted valine, leucine, isoleucine derivatives by condensation of amino acids sodium salts with benzaldehyde, salicylaldehyde, vanillin, p-chlorobenzaldehyde, 3-pyridinecarbaldehyde and subsequent reduction with sodium borohydride has been developed.

tert-Butyloxycarbonyl-L-leucyl-L-isoleucine methyl ester was prepared by the reaction of isoleucine methyl ester hydrochloride with a mixed anhydride synthesized from tert-butyloxycarbonyl-L-leucine and isobutyl chloroformate. Treatment of tert-butyloxycarbonyl-L-leucyl-L-isoleucine methyl ester with methanolic ammonia resulted in tert-butyloxycarbonyl-L-leucyl-L-isoleucinamide. L-Leucyl-L-isoleucinamide was obtained by removing the tert-butyloxycarbonyl group under the action of a dioxane solution of hydrogen chloride and the reaction of the resulting L-leucyl-L-isoleucinamide hydrochloride with triethylamine. The corresponding N-acyl derivatives of L-leucyl-L-isoleucinamide were synthesized by the reaction of L-leucyl-L-isoleucinamide with acid chlorides or p-nitrophenyl esters of acetic and benzoic acids.

The acylation of glycylglycine and its morpholide with 4,5-dichloroisothiazole-3-carbonyl chloride gave the corresponding N-(4,5-dichloroisothiazole-3-ylcarbonyl) derivatives. N-[5-(p-Tolyl)isoxazole-3-car­bonyl] analogs were synthesized by acylation of glycylglycine and its morpholide with 5-(p-tolyl)isoxazole-3-carbonyl azide since treatment of the same substrates with 5-(p-tolyl)isoxazole-3-carbonyl resulted in the formation of mixtures of products. The reactions of glycylglycine and its morpholide with phenyl N-(4,5-di­chloroisothiazol-3-yl)- and N-[(p-tolyl)isoxazol-3-yl]carbamates afforded derivatives containing an urea fragment. Some of the synthesized compounds showed antitumor activity and enhanced the antitumor effect of doxorubicin.

Synthetic routes to prolyl-leucinamide, N -benzyl(prolyl)leucinamide, and N -(prolyl-leucyl)morpholine were proposed. Treatment of these compounds with benzoyl chloride or acetyl chloride in the presence of triethylamine afforded the corresponding ( N -acylprolyl)leucinamides. Acyl derivatives of N -benzyl(prolyl)-leucinamide, and N -(prolyl-leucyl)morpholine were also synthesized by condensation of ( N -benzoylprolyl)-leucine or ( N -acetylprolyl)leucine with benzylamine or morpholine in the presence of N, N ′-dicyclohexyl-carbodiimide.

3-benzyl-6-isobutylpiperazin-2,5-dione [cyclo(leucylphenylalanyl)], 3-isobutylpiperazin-2,5-dione [cyclo(-leucylglycyl)] and 3-(sec-butyl-)-6-isobutyl-piperazine-2,5-dione [cyclo(leucylisoleucine)] have been obtained by cyclization of methyl esters of tert-butyloxycarbonyl derivatives of dipeptides, for the synthesis of which both carbodiimide-promoted peptide bond formation and the mixed anhydride method were used.

Взаимодействием смешанного ангидрида, синтезированного из третбутилоксикарбонилпролиллейцина и изо-бутилхлорформиата и вводимого в дальнейшие превращения без выделения в индивидуальном виде, с гидрохлоридом глицинамида в среде ДМФ:CH2Cl2 получен трет-бутилоксикарбонилпролиллейцилглицинамид 1. Удалением трет-бутилоксикарбонильной аминозащитной группы действием раствора хлористого водорода в диоксане или муравьиной кислотой на 1 получены гидрохлорид 2 и формиат 3 пролиллейцилглицинамида. Обработка соединения 2 эквимолярным количеством этилата натрия, а соединения 3 водным раствором аммиака давала пролиллейцилглицинамид 4.

Prolylproline has been synthesized by both classical peptide synthesis method utilizing tert -butoxycarbonyl or trifluoroacetyl protection of the NH group and carbodiimide-promoted peptide bond formation and by opening of the dioxopiperazine ring in octahydrodipyrrolo[1,2- a :1′,2′- d ]pyrazine-5,10-dione obtained by thermolysis of proline methyl ester.

Tert-butyloxycarbonylprolylleucylglycinamide is obtained both by the interaction of tert-butyloxycarbonylprol ylleucylglycine ethyl ester with a methanolic ammonia solution and by the reaction of glycine amide with a mixed anhydride which was synthesized from tert-butyloxycarbonylprolylleucine and isobutylchloroformate. The removal of the tert-butyloxycarbonyl group by the action of formic acid or a dioxane solution of hydrogen chloride and treatment of the resulting salts with the corresponding base yielded a prolylleucylglycinamide, by the interaction of which with acetic, benzoic or 5-phenylisoxazole-3-carboxylic acids chlorides acyl derivatives of prolylleucylglycinamide are obtained.

3-Benzylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione [cyclo(Pro-Phe)] was synthesized by cyclization of prolylphenylalanine and phenylalanylproline methyl esters which were prepared from the corresponding Boc-protected amino acids.

Циклические дипептиды (также известные как 2,5-дикетопиперазины), в т. ч. 3-бензилгексагидропирроло[1,2-a]пиразин-1,4-дион [(цикло(L-Pro-L-Phe)] и 3-изобутил- гексагидропирроло[1,2-a]пиразин-1,4-дион [(цикло(L-Pro-L-Leu)], проявляют противоопухолевую, противовирусную и антигипергликемическую активность, действуют как противогрибковые и антибактериальные соединения и могут найти применение в медицине.

3- Бензилгексагидропирроло[1,2-a]пиразин-1,4-дион [цикло(Pro-Phe)] получен циклизацией метиловых эфиров пролилфенилаланина или фенилаланилпролина, при синтезе которых была использована трет-бутилоксикарбонильная защитная группа.

Coordination of uranyl ion with new polydentate ligands derived from amino acids and extraction of uranium(VI) and europium(III) from aqueous salt solution into poly(ethylene glycol) phase with the use of new polydentate pincer ligands has been studied.

New preparative procedures were developed applying tert-butoxycarbonyl or trifluoroacetyl protection of amino groups in the synthesis of L-leucyl-L-isoleucine and L-isoleucyl-L-leucine.

A simple and efficient protocol is developed for the preparation of bibrachial chiral heterodentate ligands bearing two amino acid or peptide side chains on different scaffolds.

Val-Val, Val-Thr, and Thr-Val dipeptides were synthesized using trifluoroacetyl protecting group. The optical rotations of the products were similar to those of samples synthesized using Boc protection, which indicated the absence of racemization in the course of introduction and removal of trifluoroacetyl protection.

The set of data presented in this work shows that the radiolysis of hydroxyl-containing amino acids in aqueous solutions results in their degradation with -C-C- bond cleavage, which leads to both the decarboxylation of parent molecules and the removal of side substituents. The probability of these reactions mainly depends on the pH of the solution. Aminyl radicals or aminium radical cations, which are formed in the interaction of serine and threonine with ·OH radicals via the mechanism of electron or hydrogen-atom transfer from the amino groups of the parent substances, play an important role in these degradation processes.