Ashot S. Saghyan

Synthesis of 2,5‐Diarylpyrroles by Ligand‐Free Palladium‐Catalyzed CH Activation of Pyrroles in Ionic Liquids

The palladium‐catalyzed CH activation and arylation of N‐methylpyrrole and N‐phenylpyrrole allowed a convenient synthesis of diarylpyrroles. The reactions were performed by using tetrabutylammonium acetate as an ionic solvent, which allowed for the application of a ligand‐free catalytic system by using simple palladium salts or polyvinylpyrrolidone‐stabilized palladium nanoparticles as the catalyst.

A novel type of catalysts for the asymmetric C-C bond formation based on chiral stereochemically inert cationic Co-III complexes

Schiff bases derived from (1R,2R)-1,2-diaminocyclohexane and 1 eq. of salycylic (or substituted salycylic) aldehyde form stereochemically inert positively charged chiral octahedral Coiii complexes of Δ-configuration with the stereoselectivity approaching 100%. To evaluate the calatylic activity and stereoinduction of the resulting complexes with various counteranions in the outer sphere, a model reaction of trimethylsilyl cyanide addition to benzaldehyde was used. O-trimethylsilylmandelonitrile formed in the process had an enantiomeric purity up to 27%. Complexes with F− counterion showed high catalytic activity.

Using the same organocatalyst for asymmetric synthesis of both enantiomers of glutamic acid-derived Ni(II) complexes via 1,4-additions of achiral glycine and dehydroalanine Schiff base Ni(II) complexes.

Abstract(S)- and (R)-BIMBOL were efficient PT catalysts of asymmetric Michael addition of prochiral Ni–PBP–Gly (1) to acrylic esters and malonic esters to Ni–PBP–Δ-Ala (2) correspondingly. The salient feature of the catalysis is opposite configurations of Glu prepared via the two paths with BIMBOL of the same configuration and a perspective novel catalytic procedure for the synthesis of Gla derivatives.

Asymmetric Synthesis of Enantiomerically Enriched a-Amino Acids Containing 2-Furyl- and 2-Thienyl-1,2,4-triazoles in the Side-Chain

An efficient method for the asymmetric synthesis of a-amino acids, containing furyl- and thiophenyl-substituted triazoles in their side-chain, is reported. The strategy relies on Michael addition of 3,4,5-substituted 1,2,4-triazoles to the C=C bond of chiral NiII complexes containing the Schiff base formed from dehydroamino acids (dehydroalanine and (E + Z)-dehydroaminobutyric acid) and from chiral auxiliaries, i. e. (S)-2-N-(N0-benzylprolyl)aminobenzophenone and (S)-2-N- (N0-2-chlorobenzylprolyl) aminobenzophenone. The reactions proceeded with good to very good diastereoselectivity. Hydrolysis of the diastereomeric mixtures of metal complexes afforded the enantiomerically pure a-amino acids with high enantiomeric excess (ee> 98%). Graphical Abstract Asymmetric Synthesis of Enantiomerically Enriched a-Amino Acids Containing 2-Furyl- and 2-Thienyl-1,2,4-triazoles in the Side-Chain

Synthesis of optically pure ( S )-2-amino-5-arylpent-4-ynoic acids by Sonogashira reactions and their potential use as highly selective potent inhibitors of aldose reductase

A new and convenient synthesis of optically pure (S)-2-amino-5-[aryl]pent-4-ynoic acids (alkynylated amino acids) is reported. (S)-2-Aminopent-4-ynoic acid-Ni-(S)-BPB was prepared and then functionalized via Sonogashira cross-coupling reactions to give (S)-2-amino-5-[aryl]pent-4-ynoic acid-Ni-(S)-BPB. The reaction conditions for the cross-coupling reaction were optimized and twelve derivatives were synthesized. Afterwards the Ni-complexes were cleaved to obtain the free (S)-2-amino-5-[aryl]pent-4-ynoic acids with excellent optical purity. The prepared (S)-2-amino-5-[aryl]pent-4-ynoic acids were tested for biological activity and selectively showed high inhibitory activity against aldose reductase (ALR2) over ALR1. Molecular docking studies have also been carried out to identify the putative binding mode of the compounds in these enzymes.

Cyclocondensations of Substituted Thiosemicarbazides with 2-Bromo- 1,2-diphenylethan-1-one

The cyclocondensation of 4-methylthiosemicarbazide with 2-bromo-1,2-diphenylethan-1-one in ethanol afforded isomeric 2-methylamino-5,6-diphenyl-6H-3,4-thiadiazine and 2-hydrazono-3- methyl-4,5-diphenyl-2,3-dihydro-1,3-thiazole. A pyrazole was obtained by cyclocondensation and subsequent desulfurization of the thiadiazine when the reaction was carried out in concentrated hydrochloric acid. A chemical proof of the structures has been provided. The product distribution of the cyclizations strongly depends on the substitution pattern of the starting materials, and the cyclizations of methylthiosemicarbazide with 2-bromo-1,2-diphenylethan-1-one behaved considerably different from that of the analogous reactions of α-bromoacetophenone. Graphical Abstract Cyclocondensations of Substituted Thiosemicarbazides with 2-Bromo- 1,2-diphenylethan-1-one

Catalytic properties of aminoacylase of strain Rhodococcus armeniensis AM6.1

Studies of substrate specificity revealed that the D-aminoacylase of Rhodococcus armeniensis AM6.1 strain exhibits absolute stereospecificity to the D-stereoisomers of N-acetyl-amino acids. The enzyme is the most active reacted with N-acetyl-D-methionine, as well as with aromatic and hydrophobic N-acetylamino acids and interacts weakly with the basic substrates. It is practically not reacted with acidic and hydrophilic N-acetyl-amino acids. Michaelis constants (Km) and maximum reaction velocities (Vmax) were calculated, using linear regression analysis, for the following substrates: N-acetyl-D-methionine, N-acetyl-D-alanine, N-acetyl-D-phenylalanine, N-acetyl-D-tyrosine, N-acetyl-D-valine, N-acetyl-D-oxyvaline, N-acetyl- D-leucine. Substrate inhibition of D-aminoacylase was displayed with N-acetyl-D-leucine (Ks = 35.5 ± 28.3 mM) and N-acetyl-DL-tyrosine (Ks = 15.8 ± 4.5 mM). Competitive inhibition of the enzyme with product–acetic acid (Ki = 104.7 ± 21.7 mM, Km = 2.5 ± 0.5 mM, Vmax = 25.1 ± 1.5 U/mg) was observed.

Self-Assembled Ionic Composites of Negatively Charged Zn(salen) Complexes and Triphenylmethane Derived Polycations as Recyclable Catalysts for the Addition of Carbon Dioxide to Epoxides

The design and synthesis of a novel type of self‐assembled ionic composite composed of negatively charged Zn(salen) complexes and triphenylmethane derived polycations is reported. These composites were applied as easily recyclable catalysts for carbon dioxide addition to epoxides. The composites functioned as bifunctional catalysts which could be easily separated and recycled by precipitation from the reaction mixture upon addition of tetrachloromethane. The same batch of the catalyst could be employed for, at least, five runs with its catalytic properties improving as it was reused. A fully heterogeneous system was also prepared by cross‐linking leuco dye with para‐dibromoxylene and adding to it calculated amounts of Zn(salen) complex. The heterogeneous system was catalytically competent in the reaction between styrene oxide and carbon dioxide and its activity also increased on its reuse.

Synthesis of Enantiomerically Enriched Amino Acids Containing Acetylenic Bond in the Side-Chain Radical

An efficient method for the asymmetric synthesis of enantiomerically enriched derivatives of (S)-propargylglycine by С-alkylation of Ni-complex of Schiff’s bases of propargylglycine and chiral auxiliary (S)-2-N-[N’-(benzylprolyl) amino] benzophenone with benzyl bromide and its derivatives (de 85-90 %) has been developed. This resulted in synthesis of new enantiomerically enriched α-amino acids containing acetylenic bond in the side chain (ee >95%).

The inhibitory properties of new non-protein amino acids and the screening of effective analogs of L-amino acids for the selection of highly active strain-producers

We studied the antimicrobial properties of 32 new non-protein compounds synthetized in the Scientific and Production Center “Armbiotechnology” by the method of asymmetric synthesis; new analogs of L-histidine and L-isoleucine were found. Via chemical mutagenesis, we obtained new mutants of the wild strain of Brevibacterium flavum 14067 resistant to (S)-β-[4-phenyl-3-(3’-hydroxypropyl)-5-thioxo-1,2,4-thiazole-1-yl]-α-alanine (an analog of histidine) and to (2S,3R)-oxyleucine (an analog of isoleucine). It was found that the synthesis rate of histidine and isoleucine in some mutants is higher than that of most active strain-producers resistant to one of these amino acids analogs described in literature. Our data prove the efficacy of the use of new analogs as selective agents for the screening of highly active strains producing histidine and isoleucine.