H. A. Panosyan

Electric Field Effects on One-Bond Indirect Spin-Spin Coupling Constants and Possible Biomolecular Perspectives

Electric field (EF) induced changes of one-bond indirect spin-spin coupling constants are investigated on a wide range of molecules including peptide models. EFs were both externally applied and internally calculated without external EF application by the hybrid density functional theory method. Reliable agreement with experimental data has been obtained for calculated one-bond J-couplings. The role of the EF sign and direction, internal and induced components, hydrogen bonding, internuclear distance and hyperconjugative interactions on the one-bond J-coupling vs EF interconnection is analyzed. A linear dependence of 1J on EF projection along the bond is obtained, if the bound atoms possess different enough electron densities and an EF determined by the electronic polarization exists along the bond. Accentuating the 1JNH couplings as possible EF sensitive parameters, a systematic study is done in two sets of molecules with a large variation of the native internal EF value. The most EF affected component of the 1JNH coupling constant is the spin-dipole term of Ramseys formulation; however, in the total J-coupling formation, the EF influence on the Fermi contact term is the most significant. The induced EF projection along the bond is 6.7 times weaker in magnitude than the simulated external uniform field. The absolute EF dependence of the one-bond J-coupling involves only the internal field, which is the sum of the induced field (if the external field exists) and the internuclear field determined by the native polarization. That linear and universal dependence joins the corresponding couplings in a diverse set of molecules under various electrostatic conditions. Many types of the one-bond J-couplings can be potentially measured in biomolecules, and the study of their relation with the electrostatic properties at the corresponding sites opens a new avenue to the full exploitation of the NMR measurable parameters with novel and exciting applications.

A New Approach to the Efficient Method for the Asymmetric Synthesis of (S)-O-, M-, P-Fluorophenylalanines and Their 2-Methyl-substituted Analogs

Abstract The reactions of asymmetric C-alkylation of glycine and alanine in NiII complexes of their Schiffs bases with modified chiral auxiliaries (S)-2-N-[(N′-2-chlorobenzylprolyl)amino]benzophenone and (S)-2-N-[N′-(3,4-dimethylbenzylprolyl)amino]benzophenone by fluorine-substituted benzyl halogenides have been studied. As a result, a highly stereoselective and relatively rapid method for the asymmetric synthesis of (S)-o-, m-, p-fluorophenylalanines and their 2-methyl substituted analogs has been developed.

The role of retro-Michael reaction in the synthesis of 5-carbamoyl-2-pyridones by reaction of dialkyl ethoxymethylidenemalonates with acetoacetamides

The reaction of dialkyl ethoxymethylidenemalonates with arylamides of acetoacetic acid was studied for the purpose of creating a new method for the synthesis of substituted 2-pyridones containing a carbamoyl group. This reaction was shown to occur in the presence of triethylamine in ethanol solution at room temperature, forming mainly retro-Michael products, N,1-diaryl-5-acetyl-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxamides. Simultaneously, depending on the molar ratio of reagents, triethylammonium 5-acetyl-3-alkoxycarbonyl-1-aryl-6-oxo-1,6-dihydropyridin-2-olates were also formed at the same time. The results of this reaction can be explained by the different acidity of the acidic hydrogen atoms in Michael adduct.

Anti-human immunodeficiency activity of novel 2-arylpyrrolidine analogs

A series of 26 new compounds were synthesized and screened for their anti-human immunodeficiency virus-1 and cytotoxicity activity. Of these, 14 were found to be inhibitors of human immunodeficiency virus replications in primary human lymphocytes with 50 % effective concentration values <20 µM. Moreover, most of the compounds were cytotoxic to human lymphocytes, CEM, and Vero cells. Our structure activity relationship study identified different patterns. Compounds 2g–j and 4 (whose structure is closer to the loviride structure) were very potent. Comparing the activity of the compounds containing the 2-aryl substituents, we observed that compounds with benzyloxyphenyl groups were more potent. Compounds in which the 1-aryl moiety contained methyl group in 4- or 3,5-positions also showed high activity. In the series of compounds containing the nitrile, amine, and amide groups, we observed a decrease in activity with CN > NH2 > C(O)NH2. The difference of activity between the 5-membered and 4-membered rings compounds was not significant. This initial information could be used to design improved anti-human immunodeficiency virus compounds in this class.

Synthesis of new derivatives of 5-(3,4-dihydro-2Н-pyrrol-5-yl)-pyrimidine

By one-stage condensation of 6-(arylamino)pyrimidine-2,4(1Н,3Н)-diones with pyrrolidin-2-one new potential antiviral compounds were obtained, analogs of pyrrolinylpyrimidine containing structural fragments of known drugs AZT and HEPT used in treating HIV-infections.

One-step synthesis of pyrido[2,3-d]pyrimidines, amides, and benzoxazolylethylpyrimidine by condensation of substituted 3-(2-phenylpyrimidin-5-yl)propanoic acids with aromatic amines in polyphosphoric acid

Depending on the reactant structure, reactions of substituted 3-(2-phenylpyrimidin-5-yl)propanoic acids with 2-aminopyridine, p-toluidine, and 2-aminophenol in polyphosphoric acid afforded the corresponding N-(pyridin-2-yl)propanamides, 5-[2-(benzoxazol-2-yl)ethyl]pyrimidine, and pyrido[2,3-d]pyrimidinones.

Base-catalyzed Intramolecular Diels–Alder Cyclization of Dialkyl(3-arylprop-2-yn-1-yl)-(3-phenylprop-2-en-1-yl)ammonium Bromides in Aqueous Solution

Dialkyl(3-arylprop-2-yn-1-yl)(3-phenylprop-2-en-1-yl)ammonium bromides, in contrast to their allyl analogs containing a 3-arylprop-2-en-1-yl group, undergo cyclization in aqueous solution in the presence of base upon prior heating to give potentially biologically active 2,2-dialkyl-6-chloro-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromides in almost quantitative yield. Heat is released in the course of these reactions. We found that the introduction of a phenyl group at position 3 of the allyl fragment facilitates the cyclization. This is the first report of a base-catalyzed intramolecular cyclization of allyl analogs of dialkyl(3-arylprop-2-yn-1-yl)ammonium salts.

Cyclization of dialkyl(3-phenylpropen-2-yl)-(3-phenylpropyn-2-l)ammonium bromides by the action of an aqueous alkali solution. aqueous-alkaline cleavage of the cyclization products – n,n-dialkyl-4(9)-phenyl-3a,4-dihydro-benzo[f]isoindolinium bromides

When heated in an alkaline aqueous medium, dialkyl(3-phenylpropen-2-yl)(3-phenylpropyn-2-yl)- ammonium bromides undergo intramolecular cyclization, forming N,N-dialkyl-4(9)-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromides. The cyclization products undergo aqueous-alkaline cleavage at the C(1)–N(2) or N(2)–C(3) bond, which leads to a mixture of 2-(dialkylaminomethyl)-3-methyl- and 3-(dialkylaminomethyl)-2-methyl-1-phenylnaphthalenes. However, only the C(1)–N(2) bond cleavage product is formed in the case of 2,2-pentamethylene-9-phenyl-3a,4-dihydrobenzo-[f]isoindolinium bromide.

Synthesis and Structure of New Substituted Pyrimidinone with Unsaturated Side Chain

Melting of a mixture of 5-substituted 2,4-dimethyl-1,6-dihydropyrimidin-6-ones with cinnamic aldehyde, 1-methylindoline-2,3-dione and 6-methoxy-2-chloroquinoline-3-carbaldehyde in the presence of ZnCl2 led to the formation of substituted pyrimidines with conjugated bonds in the position 2. The structure of synthesized compounds as 2-isomers was confirmed by 2D 1H NMR NOESY data.

4-alkylated 2-(2,3,5-tri-O-acyl-β-D-ribofuranosyl)- and 2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1,2,4-triazine-3,5-diones

The alkylation of 2-(2,3,5-tri-O-acyl-β-D-ribofuranosyl)- and 2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)- 1,2,4-triazine-3,5-diones with benzyl halides afforded the corresponding 4-benzyl derivatives whose structure was determined by spectral methods, including X-ray analysis. Some of the synthesized compounds were tested for antibacterial and antitumor activity.