V. A. Knizhnikov

Pincer ligands based on α-amino acids: I. Synthesis of polydentate ligands from pyrrole-2,5-dicarbaldehyde

New chiral pincer ligands having CH=N moieties were synthesized by condensation of 1H-pyrrole-2,5-dicarbaldehyde with l-methionine and l-histidine methyl esters. Their reduction under mild conditions (NaBH4, −30°C) gave the corresponding amine ligands in high yields. An improved procedure for the preparation of 1H-pyrrole-2,5-dicarbaldehyde was proposed.

N-trifluoroacyl lysine derivatives in the synthesis of L-Lysyl-L-glutamic acid

Conditions were developed for simultaneous preparation of Nå-trifluoroacetyl-L-lysine and Nα,Nå-bis(trifluoroacetyl)-L-lysine at overall conversion of initial lysine monohydrochloride up to 82%. By reaction of dimethyl L-glutamate with Nα,Nå-bis(trifluoroacetyl)-L-lysyl chloride in the presence of triethylamine or with Nα-carboxyanhydride of Nå-trifluoroacetyl-L-lysine with subsequent removing protecting groups in the formed dipeptides by treating with water-ethanol solution of sodium hydroxide we obtained L-lysyl-L-glutamic acid. Physicochemical characteristics of samples obtained coincided with characteristics of L-lysyl-L-glutamic acid described in the literature thus suggesting that no racemization occurred either at the stage of peptide bond formation or at deprotection.

N-trifluoroacetyl-β-alanine in the synthesis of carnosine

Conditions have been developed for the synthesis of N-trifluoroacetyl-β-alanine, N-tifluoroacetyl-β-alanyl chloride, and N-trifluoroacetyl-β-alanine 4-nitrophenyl ester. These compounds reacted with histidine methyl ester or sodium salt to give N-trifluoroacetyl-β-alanyl-l-histidine methyl ester CF3CONHCH2CH2·CONHCH(CH2C3H3N2)COOCH3 and N-trifluoroacetyl-β-alanyl-l-histidine CF3CONHCH2CH2CONHCH·(CH2C3H3N2)COOH. Their hydrolysis with a solution of sodium hydroxide in aqueous ethanol, followed by acidification with trifluoroacetic acid, led to the formation of β-alanyl-l-histidine (l-carnosine).

Pincer ligands based on α-amino acids: III. New ligands based on 4-substituted phenols and their copper complexes. Enantioselective recognition of tyrosine

Reactions of L-methionine, L-serine, and L-valine with 5-substituted-2-hydroxybenzene-1,3-dicarbaldehydes gave a series of chiral Schiff base pincer ligands which were reduced to the corresponding diamines. The new Schiff base ligands reacted with copper(II) chloride to form dinuclear copper complexes which were found to be capable of recognizing tyrosine enantiomers in aqueous solution. The structure of the complexes was determined on the basis of their spectral parameters.

N-Benzyl Derivatives of Leucine Esters

Leucine methyl and ethyl esters reacted with 3-bromobenzaldehyde and 4-chlorobenzaldehyde in anhydrous methanol in the presence of magnesium sulfate to afford the coresponding Schiff bases of the general formula (CH3)2CHCH2CH(COOR1)N=CHR2 [R1 = CH3, C2H5, R2= 3-BrC6H4, 4-ClC6H4]. Their reduction with sodium tetrahydridoborate yielded N-benzyl derivatives (CH3)2CHCH2CH(COOR1)NHCH2R2, which were converted into N-acyl-N-benzyl derivatives (CH3)2CHCH2CH(COOR1)N(COR3)CH2R2[R3= CH3, C6H5].

Azomethines on the basis of sodium salts of valine and leucine

Sodium salts of valine and leucine [RCH(NH2)COONa, R = (CH3)2CH, (CH3)2CHCH2] were reacted with benzaldehyde and its derivatives to obtain azomethines RCH(COONa)N = CHAr (Ar = C6H5, 2-ClC6H4, 4-ClC6H4, 2-HOC6H4, 4-HOC6H4). The structure of the products was proved by IR and 1H NMR spectroscopy, mass spectrometry, and elemental analysis.

Complexation of uranium(VI) and europium(III) with new polydentate pincer ligands in aqueous systems

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.

Synthesis of L-leucyl-L-isoleucine and L-isoleucyl-L-leucine

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.

Pincer Ligands Based on α-Amino Acids: V. * New Generation Chiral Receptors for the Recognition of Amino Acid Enantiomers in Aqueous Environment

Selective recognition of enantiomers of amino acids valine, methionine, phenylalanine, serine, and tyrosine by a binuclear copper complex with an azomethine obtained from 2,6-diformyl-4-methylphenol and L-valine was studied by means of spectrophotometry. The binding constants of individual enentiomers were estimated for valine, phenylalanine, methionine, serine, and tyrosine, and the enantioselectivity factors were evaluated. The isomers of serine and tyrosine (with respect to the first stage) were recognized with a considerable enantioselectivity (1.34 and 5.46 respectively), whereas the binding constants of valine and phenylalanine enantiomers are virtually indistinguishable.

Pincer ligands based on α-amino acids: IV. Schiff bases derived from pyridine-2,6-dicarbaldehyde. Synthesis and intramolecular dynamics

A number of pincer Schiff base and amine ligands were synthesized from pyridine-2,6-dicarbaldehyde and α-amino acids, L-methionine and L-serine. The Schiff base derived from L-serine was shown to exist as an equilibrium mixture with diastereoisomeric oxazolidines. The ring-chain tautomerism was confirmed by the results of reduction of the azomethine bond. The reduction products, pincer amines, exist in solution as mixtures of conformers differing in the degree of aggregation of the amino acid residues.