Design of new imidazole derivatives with anti-HCMV activity: QSAR modeling,synthesis and biological testing

Journal of Computer-Aided Molecular Design - The problem of designing new antiviral drugs against Human Cytomegalovirus (HCMV) was addressed using the Online Chemical Modeling Environment (OCHEM)....     

Investigation of intermolecular interactions in perylene films on Au(111) by infrared spectroscopy

Intermolecular interactions in crystalline perylene films on Au(111) have been investigated by Fourier transform infrared spectroscopy. Dimer modes of vibrations are observed in the crystalline film, in contrast to the monomer modes found for isolated perylene molecules. These dimers are formed via hydrogen bonding in the sandwich herringbone structure of the crystalline α-phase. Davydov splitting of both the monomer and the dimer modes is observed due to resonance dynamic intermolecular interaction. The splitting of monomer modes into three distinct vibrations and the occurrence of the dimer modes confirm that the film crystallizes in the α phase, which is in line with the x-ray diffraction results. The frequency shift and band broadening at elevated temperature have been attributed to the cubic and quartic anharmonic interactions.     

Synthesis of Chiral Tetrasubstituted Azetidines from Donor–Acceptor Azetines via Asymmetric Copper(I)‐Catalyzed Imido‐Ylide [3+1]‐Cycloaddition with Metallo‐Enolcarbenes

The all‐cis stereoisomers of tetrasubstituted azetidine‐2‐carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl‐protected Z‐γ‐substituted enoldiazoacetates and imido‐sulfur ylides by asymmetric [3+1]‐cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p‐methoxybenzyl azetine‐2‐carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.     

Convenient Approach to 10- and 11-Membered Azalactams

A convenient method for the synthesis of 10- and 11-membered azalactams via reductive cleavage of bicyclic systems featuring an amidine fragment was studied. It was found that the ring-expansion reaction of bicyclic dihydropyrimidones depends on the ring size of saturated fragment, substituents in the pyrimidone core and reaction conditions. A new efficient method for the synthesis of medium ring azalactams by reductive cleavage of quaternary salts of annulated dihydropyrimidones was proposed as well. The obtained medium ring azalactams with a secondary amine function were used in the synthesis of bicyclic heteroaromatic systems.     

An optimization technique based on a vector autoregression model with state space representation: application to Ukrainian cargo transport data

This paper proposes to forecast indicators of the Ukrainian cargo transport system, taking into account their relations with macroeconomic indicators. Increased forecast accuracy at a priori information uncertainty is attained through an optimization technique, starting with a Vector Autoregression (VAR) model of observed multiple time series, its state space representation and subsequent adaptive filtering. The adaptive filter, earlier proposed by the authors, minimizes forecasting errors. Under an optimization criterion, the information divergence of Kullback–Leibler between probability distributions of real values and their estimations is established. The main advantage of the proposed technique is connected with the opportunity to estimate future values of multiple time series even in presence of structural breaks (describing the changes of the status ‘before crisis’ / ‘after crisis’). The observations are available from 2003:1–2011:12, the analysis is performed for the period 2003:1–2011:9. In-sample forecasting of multiple time series of cargo volumes transferred by different transport modes and two macro indicators is compared with the forecast based on a VAR model. In-sample forecast is realized for the last three months 2011:10–2011:12.     

Distinguishing two isomeric mephedrone substitutes with selective reagent ionisation mass spectrometry (SRI‐MS)

The isomers 4‐methylethcathinone and N‐ethylbuphedrone are substitutes for the recently banned drug mephedrone. We find that with conventional proton transfer reaction mass spectrometry (PTR‐MS), it is not possible to distinguish between these two isomers, because essentially for both substances, only the protonated molecules are observed at a mass‐to‐charge ratio of 192 (C₁₂H₁₈NO⁺). However, when utilising an advanced PTR‐MS instrument that allows us to switch the reagent ions (selective reagent ionisation) from H₃O⁺ (which is commonly used in PTR‐MS) to NO⁺, O₂⁺ and Kr⁺, characteristic product (fragment) ions are detected: C₄H₁₀N⁺ (72 Da) for 4‐methylethcathinone and C₅H₁₂N⁺ (86 Da) for N‐ethylbuphedrone; thus, selective reagent ionisation MS proves to be a powerful tool for fast detection and identification of these compounds. Copyright © 2013 John Wiley & Sons, Ltd.     

Site-Selective Late-Stage Aromatic [18F]Fluorination via Aryl Sulfonium Salts

Site-selective functionalization of C−H bonds in small complex molecules is a long-standing challenge in organic chemistry. Herein, we report a broadly applicable and site-selective aromatic C−H dibenzothiophenylation reaction. The conceptual advantage of this transformation is further demonstrated through the two-step C−H [¹⁸F]fluorination of a series of marketed small-molecule drugs.     

Oxa-spirocycles: synthesis,properties and applications

A general approach to a new generation of spirocyclic molecules – oxa-spirocycles – was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of an oxygen atom into the spirocyclic unit dramatically improved water solubility (by up to 40 times) and lowered lipophilicity. More potent oxa-spirocyclic analogues of antihypertensive drug terazosin were synthesized and studied in vivo.

A general practical approach to a new generation of spirocyclic molecules – oxa-spirocycles – is developed.     

Strain-Induced Nucleophilic Ring Opening of Donor–Acceptor Cyclopropenes for Synthesis of Monosubstituted Succinic Acid Derivatives

1,2,3-Trisubstituted donor–acceptor cyclopropenes (DACPs) generated in situ from enoldiazo compounds react with nucleophiles to form α-substituted succinic acid derivatives in high yields. Initial dirhodium(II) carboxylate catalysis rapidly converts enoldiazo-acetates or -acetamides to DACPs that undergo catalyst-free Favorskii ring opening with amines, and also with anilines, alcohols, and thiols, when facilitated by catalytic amounts of 4-dimethylaminopyridine (DMAP). This methodology provides easy access to mixed esters and amides of monosubstituted succinic acids, including derivatives of naturally occurring compounds. It also affords dihydrazide, dihydroxamic acid, and diamide derivatives, as well as α-substituted tetrahydropyridazine-3,6-diones in high yields. Attempts to generate optically enriched DACPs were not successful because their populations having the R and S configurations formed with a chiral dirhodium catalyst are quite similar, and the loss of enantiocontrol likely originates from the DACP ring forming step which is reversible with its intermediate metal carbene.