Synthesis of 2-azirine-2,2-dicarboxylic acids and their derivatives.

Methods for the preparation of 3-aryl-2-azirine-2,2-dicarboxylic acids and their amides, esters, and azides by FeCl-catalyzed isomerization of 3-aryl-5-chloroisoxazole-4-carbonyl chlorides into 3-aryl-2-azirine-2,2-dicarbonyl dichlorides followed by their reaction with nucleophiles are reported. Two approaches to the preparation of 3-aryl-5-chloroisoxazole-4-carbonyl chlorides have been developed.

Dual-Reporter SARS-CoV-2 Replicon for Screening Viral Polymerase Inhibitors.

To design a safe cellular system for testing inhibitors targeting the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, a genetic construct was engineered containing viral cDNA with two blocks of reporter genes while the genes encoding structural S, E, and M proteins were absent. The first reporter block, consisting of Renilla luciferase and green fluorescent protein (Rluc-GFP), was located upstream of the SARS-CoV-2 5'-UTR. Meanwhile, the second block represented by firefly luciferase and red fluorescent protein (Fluc-RFP) was positioned downstream of the transcription regulatory sequence (TRS-N).

DBU-Promoted Cyclizations of Cyclopentyl-Substituted Oxazapolyenes to Cyclopentapyridones and Hydroxypyrroles: Experimental and DFT Study.

1,1-Di(alkoxycarbonyl)-4-cyclopentyl-2-azabuta-1,3-dienes react with DBU to form two types of heterocyclic products: 1-cyclopenta[]pyrid-1-ones and 3-hydroxy-1-pyrroles. These previously unobserved transformations proceed through the formation of 1-azapentadienyl anion which undergoes 1,6-shift of the alkoxycarbonyl group to the cyclopentyl moiety followed by 1,6-cyclization to form the cyclopentapyridone (path ) and 1,5-cyclization accompanied by 1,3-shift of the methoxy group followed by dialkyl carbonate elimination to afford the hydroxypyrrole (path ). The mechanisms of the reactions were studied using DFT calculations.

[Cytotoxicity Studies of 5-Arylaminouracil Derivatives].

We have previously shown that 5-arylaminouracil derivatives can inhibit HIV-1, herpesviruses, mycobacteria, and other pathogens through various mechanisms. The purpose of this study was to evaluate the potential of 5-arylaminouracils and their derivatives against leukemia, neuroblastoma, and glial brain tumors. 5-Aminouracils with various substituents and their 5'-norcabocyclic and ribo derivatives were screened for cytotoxicity against two neuroblastoma cell lines (SH-SY5Y and IMR-32), K-562 lymphoblastic cells, HL-60 promyeoloblastic cells, and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138).

Frequency-Domain Features and Low-Frequency Synchronization of Photoplethysmographic Waveform Variability and Heart Rate Variability with Increasing Severity of Cardiovascular Diseases.

-Heart rate variability (HRV) and photoplethysmographic waveform variability (PPGV) are available approaches for assessing the state of cardiovascular autonomic regulation. The goal of our study was to compare the frequency-domain features and low-frequency (LF) synchronization of the PPGV and HRV with increasing severity of cardiovascular diseases. -Our study included 998 electrocardiogram (ECG) and finger photoplethysmogram (PPG) recordings from subjects, classified into five categories: 53 recordings from healthy subjects, aged 28.

The concept of Gallium-controlled double C-H functionalization of aliphatic CH-groups driven by Vinyl carbocations.

The direct C-H activation of inert C(sp)-H bonds in a hydrocarbon chain has been a very attractive target in organic synthesis for many decades. Among all the variety of processes, those driven by vinyl carbocations are quite scarce thus far, and it is hard to control for unstabilized vinyl cations. In this study, we designed a double C(sp)-H functionalization of unactivated alkyl CH groups to produce a totally substituted quaternary carbon stereocenter via insertion of vinyl carbocations.

Rhodium-Catalyzed Double Dearomatization of 1,2,3-Triazole-Isoxazole Dyads: Synthesis of Nonfused 1-1,3-Diazepines.

A double dearomatization of dyads consisting of 1-sulfonyl-1,2,3-triazoles and 3-aryl-5-methoxyisoxazoles was applied for the efficient synthesis of nonfused 1-1,3-diazepines. The plausible mechanism of the cascade reaction includes transformation of the 1,2,3-triazole to rhodium azavinyl carbene, the -selective hydride shift to form the 1-azabuta-1,3-diene moiety, rhodium-catalyzed ring contraction of the isoxazole to azirine, and pseudopericyclic four-atom ring expansion of the azirine. The synthetic utility and antiproliferative activity of the 1,3-diazepines obtained have been demonstrated.

Left Ventricular Diastolic Dysfunction in Cardiac Surgery: A Narrative Review.

Cardiac relaxation is a complex process that involves various interconnected characteristics and, along with contractile properties, determines stroke volume. Perioperative ischemia-reperfusion injury and left ventricular diastolic dysfunction (DD) are characterized by the left ventricle's inability to receive a sufficient blood volume under adequate preload. Baseline DD and perioperative DD have an impact on postoperative complications, length of hospital stay, and major clinical outcomes in a variety of cardiac pathologies.

Preclinical Immunogenicity and Efficacy Studies for Therapeutic Vaccines for Human Papillomavirus-Type-16-Associated Cancer.

The objective of this study was to conduct preclinical immunogenicity and efficacy studies with several therapeutic vaccines for human papillomavirus (HPV)-16-associated cancers expressing the early antigens E5, E6, and E7 with or without E2. The viral oncoproteins were either expressed by themselves as fusion proteins or the fusion proteins were inserted genetically into herpes simplex virus (HSV)-1 glycoprotein D (gD) which, upon binding to the herpes virus entry mediator (HVEM), inhibits an early T cell checkpoint mediated by the B and T cell mediator (BTLA). This, in turn, lowers the threshold for T cell activation and augments and broadens CD8 T cell responses to the antigens.

Cyclocondensation of 2-(α-Diazoacyl)-2-azirines with Amidines in Diazo Synthesis of Functionalized Naphtho[1,2-]imidazoles.

A diazo approach toward functionalized naphtho[1,2-]imidazole derivatives has been developed. It involved a new reaction of arylamidines with 2-(α-diazoacyl)-2-azirines giving 5-aryl-4-(α-diazoacyl)-1-imidazoles under mild conditions in good yields. The mechanism of annulation of azirines with amidines is discussed based on DFT calculations.

Stable 2-Azaallyl Salts as a Bridge between 2-Azirines and Densely Functionalized 2-Pyrroles.

An efficient protocol for the synthesis of stable 2-azaallyl anion salts by the reaction of alkyl 2-bromo-2-azirine-2-carboxylates with trimethylsilyl cyanide/BuNF has been developed. The domino reaction proceeds in four steps via the cleavage of the azirine C-C bond to provide the tetrabutylammonium salts of stereochemically pure 2-azaallyl anions having U-configuration relative to the cyano groups. The anions with an -substituted aryl group or styryl group exist as a mixture of two geometrical isomers across the N2-C3 bond.

Acridine-Isoxazole and Acridine-Azirine Hybrids: Synthesis, Photochemical Transformations in the UV/Visible Radiation Boundary Region, and Anticancer Activity.

Easy-to-handle -hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine-azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320-420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition.

In Vivo and In Vitro Analysis of Toxicity of a Prospective Magnetic Resonance Contrast Agent Based on Arabinogalactan and Gadolinium Nanocomposite.

We studied the cytotoxic effect of gadolinium nanocomposite on cultured mouse fibroblasts 3T3-SV40 and histological changes in the liver tissue of albino rats after its administration. For in vitro experiment, gadolinium nanocomposite on the natural matrix of arabinogalactan (nGd-AG) was dissolved in DMEM nutrient medium to concentrations of 0.005, 0.

Divergent Synthesis of Pyrazolo[1,5-]pyridines and Imidazo[1,5-]pyridines via Reagent-Controlled Cleavage of the C-N or C-C Azirine Bond in 2-Pyridylazirines.

The three-membered ring in 2-(2-pyridyl)azirine-2-carboxylic esters and thioesters can undergo selective cleavage of either the N-C2 bond under copper(II) catalysis or the C-C bond under the action of HCl to provide isomeric azirine ring expansion products of pyrazolo[1,5-]pyridine or imidazo[1,5-]pyridine series, respectively. Mild catalytic reaction conditions for the formation of pyrazolopyridines make it possible to obtain them directly from 4-bromoisoxazoles by a one-pot, three-stage procedure without isolating the intermediate 2-bromoazirines and 2-(2-pyridyl)azirines.

Divergent Diazo Approach toward Alkyl 5/4-Hydroxy-3-benzo[]indole-4/5-carboxylates.

A divergent diazo approach toward alkyl 5/4-hydroxy-3-benzo[]indole-4/5-carboxylates has been developed. The reaction of 1,3-diketones with alkyl 2-diazo-3-oxo-3-(2-azirin-2-yl)propanoates catalyzed by Co(acac) or Ni(acac) gives various alkyl 3-(1-pyrrol-2-yl)-2-diazo-3-oxopropanoate in good yields. The latter undergo Wolff rearrangement followed by the 6π-cyclization of transient ketene to form alkyl 5-hydroxy-3-benzo[]indole-4-carboxylates bearing various substituents in positions 1, 2, 7, and 8, as well as derivatives of methyl 4-hydroxy-6-thieno[2,3-]indole-5-carboxylates and methyl 5-hydroxy-7-benzo[]carbazole-6-carboxylate under thermolysis or Rh(OAc) catalysis.

[2 + 2] Cycloaddition/Retro-Electrocyclization/Decarboxylation Reaction Sequence: Access to 4-Aminopyridines from Methylideneisoxazolones and Ynamines.

4-(1-Aminoallylidene)isoxazol-5-ones were synthesized in good yields by the [2 + 2]cycloaddition-retro-electrocyclization reaction of 4-methylideneisoxazol-5(4)-ones with ynamines. The reaction mechanism and the absence of hetero-Diels-Alder cycloadducts were investigated by DFT calculations. 4-(1-Aminoallylidene)isoxazol-5-ones were found to be convenient substrates for the preparation of 4-aminopyridines under thermal metal-free conditions.

Tandem Cycloaddition of Azides to 3,3-Diaminoacrylonitriles (2-Cyanoacetamidines) and Cornforth-Type Rearrangement as an Approach to 5-Amino-1,2,3-triazole-4--substituted Imidamides.

An efficient base-catalyzed, metal-free method for the synthesis of 5-amino-1,2,3-triazole-4--sulfonyl- and arylimidamides, directed by the structure of the amidine group, has been developed. It is based on a previously unknown tandem process involving cycloaddition reaction to 3,3-diaminoacrylonitriles (2-cyanoacetamidines) with aryl(alkyl)sulfonyl or aryl azides and Cornforth-type rearrangement. During the reaction optimization, different factors were found to facilitate the title reaction, which include the use of a strong base and -mono- or ,'-disubstituted 3,3-diaminoacrylonitriles.

Synthesis of 1-[ω-(Bromophenoxy)alkyl]-3-naphthalenylmethyl Derivatives of Uracil and Their Analogues As Probable Inhibitors of Human Cytomegalovirus Replication.

The synthesis of a new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing in position 3 naphthalen-1-yl-, naphthalen-2-yl-, 1-bromonaphthalen-2-ylmethyl, benzyl, and anthracene 9-methyl fragment was carried out. The antiviral properties of the synthesized compounds were studied against human cytomegalovirus. It was found that the compound that contained a bridge of five methylene groups has a high anti-cytomegalovirus activity in vitro.

Triethylamine-Promoted Oxidative Cyclodimerization of 2-Azirine-2-carboxylates to Pyrimidine-4,6-dicarboxylates: Experimental and DFT Study.

An unprecedented oxidative cyclodimerization reaction of 2-azirine-2-carboxylates to pyrimidine-4,6-dicarboxylates under heating with triethylamine in air is described. In this reaction, one azirine molecule undergoes formal cleavage across the C-C bond and another across the C=N bond. According to the experimental study and DFT calculations, the key steps of the reaction mechanism include nucleophilic addition of ,-diethylhydroxylamine to an azirine to form an (aminooxy)aziridine, generation of an azomethine ylide, and its 1,3-dipolar cycloaddition to the second azirine molecule.

Compensatory mechanisms of reduced interhemispheric EEG connectivity during sleep in patients with apnea.

We performed a mathematical analysis of functional connectivity in electroencephalography (EEG) of patients with obstructive sleep apnea (OSA) (N = 10; age: 52.8 ± 13 years; median age: 49 years; male/female ratio: 7/3), compared with a group of apparently healthy participants (N = 15; age: 51.5 ± 29.

Boronyl Borinic Esters: Preparation as B pin / BuLi/TFAA Adducts, Structural Insights and Reactivity in Pd-catalyzed Allylic Borylation.

Novel boronyl borinic ester I was generated by quenching the B pin / BuLi-ate complex with trifluoroacetic acid anhydride (TFAA) via ring-opening in the 1,3,2-dioxaborolane moiety on ate-boron. Detailed NMR studies of the B pin / BuLi-ate complex in solution and in solid state allowed us to assume its oligomeric nature in solids with only ate-boron involved in the oligomerization process. The O-trifluoroacetyl pinacolate residue on borinic ester I initially formed on quenching with TFAA undergoes an unusual intramolecular transesterification with the carbonyl group of trifluoroacetyl forming othroester moiety in a few hours at r.

A Complex of Marine Geophysical Methods for Studying Gas Emission Process on the Arctic Shelf.

The Russian sector of the arctic shelf is the longest in the world. Quite a lot of places of massive discharge of bubble methane from the seabed into the water column and further into the atmosphere were found there. This natural phenomenon requires an extensive complex of geological, biological, geophysical, and chemical studies.

Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3.

Bacterial cystathionine γ-lyase (bCSE) is the main producer of HS in pathogenic bacteria such as , , etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[]thiophen-2-yl)-1-indol-1-yl)methyl)- 1-pyrazole-5-carboxylic acid (NL3), have been developed.

A new view on the mechanism of UV photodegradation of the tricyclic antidepressant carbamazepine in aqueous solutions.

Mechanism of direct UV photolysis of the tricyclic antidepressant carbamazepine (CBZ) at neutral pH was revealed by a combination of nanosecond laser flash photolysis, steady-state photolysis combined with high resolution LC-MS and DFT quantum-chemical calculations. The detection of short-lived intermediates and the detailed identification of final products were performed for the first time. The quantum yield of CBZ photodegradation (282 nm) is about 0.