Cascade Synthesis of Pyrrolo[1,2-]quinolines and Pyrrolo[2,1-]isoquinolines via Formal [3 + 2]-Cycloaddition of Push-Pull Nitro Heterocycles with Carbonyl-Stabilized Quinolinium/Isoquinolinium Ylides.

Various substituted pyrrolo[1,2-]quinolines and pyrrolo[2,1-]isoquinolines were synthesized in good to high yields by the EtN-mediated reaction of push-pull 3-nitrobenzofurans or 1-Ts-/1-Ms-3-nitroindoles and precursors of carbonyl-stabilized quinolinium and isoquinolinium ylides as 1,3-dipole equivalents. These transformations proceed in a one-pot manner starting with the formal [3 + 2]-cycloaddition stage, which is accompanied by double dearomatization of both quinoline/isoquinoline and benzofuran/indole moieties, followed by ring-opening of cyclic intermediate formed and nitrous acid elimination sequence. [3 + 2]-Cycloadducts were isolated as the final products in cases of impossibility or difficulty of their enolization.

Molecular Dynamics Simulation of SARS-CoV-2 E Ion Channel: The Study of Lone Protein and its Conformational Changes in Complex with Potential Cage Inhibitors.

Background: The coronavirus E ion channel has previously been studied as a potential target for antiviral therapy, with several compounds found to bind to the channel. However, these compounds have low activity, searching for effective E ion channel inhibitors of great importance.

Objective: This study aimed to develop a computational approach for designing ligands for the coronaviral E ion channel and identify potential inhibitors based on this approach.

Divergent Transformations of 2-Nitro-1-benzo[]chromenes in Reactions with Alkylidenemalononitriles: Access to Naphtho[2,1-]furans via Base-Mediated Pyran Ring Contraction.

The action of 2-(1-arylethylidene)malononitriles on 2-nitro-1-benzo[]chromenes in the presence of EtN and MoO·2HO results in naphtho[2,1-]furans containing an allylidenemalononitrile unit in the α-position. The reaction proceeds with contraction of the pyran ring via a cascade carba-Michael addition/retro-oxa-Michael reaction/tautomerization/S2/oxidation process. In contrast, the reaction of 2-nitro-1-benzo[]chromenes with the cyclic Knoevenagel adduct derived from 1-indanone and malononitrile leads to dihydroindeno[1,2-]xanthenes.

Catalyst-free formal [3 + 2] cycloaddition of stabilized ,-cyclic azomethine imines to 3-nitrobenzofurans and 3-nitro-4-chromenes: access to heteroannulated pyrazolo[1,2-]pyrazoles.

We have studied the [3 + 2]-cycloaddition of various ,-cyclic azomethine imines to 3-nitrobenzofurans. This process is a rare example of their dearomatization. We have also extended this process to the related 3-nitro-4-chromenes as dipolarophiles.

Three-Component Condensation of Pyridinium Ylides, β-Ketonitriles, and Aldehydes with Divergent Regioselectivity: Synthesis of 4,5-Dihydrofuran-3- and 2-Pyran-5-carbonitriles.

A library of -4,5-dihydrofuran-3-carbonitriles was synthesized in a diastereoselective manner in good yields by the three-component reaction of β-ketonitriles, carbonyl- and semistabilized pyridinium ylide precursors, and aldehydes in the presence of piperidine. This one-pot transformation generates two C-C and one C-O bond and proceeds through a cascade Knoevenagel condensation, a Michael addition, and intramolecular S2 cyclization. Formation of cyclopropanecarbonitrile derivatives, which in some cases were obtained as major products, was found to be a competing reaction.

Eco-friendly synthesis of fused pyrano[2,3-]pyrans ammonium acetate-mediated formal oxa-[3 + 3]cycloaddition of 4-chromene-3-carbaldehydes and cyclic 1,3-dicarbonyl compounds.

Various substituted polycyclic pyrano[2,3-]pyrans were synthesized the condensation of 4-chromene-3-carbaldehydes and their areno-condensed analogues with hetero- and carbocyclic 1,3-dicarbonyl compounds in acetic acid. Ammonium acetate was used as a green catalyst for the reaction. The process also involves the subsequent Knoevenagel condensation and 6π-electrocyclization of the 1-oxatriene intermediates formed.

Synthesis, in vitro and in vivo evaluation of 2-aryl-4H-chromene and 3-aryl-1H-benzo[f]chromene derivatives as novel α-glucosidase inhibitors.

Herein we report a study of novel arylchromene derivatives as analogs of naturally occurring flavonoids with prominent α-glucosidase inhibitory properties. Novel inhibitors were identified via simple stepwise in silico screening, efficient synthesis, and biological evaluation. It is shown that 2-aryl-4H-chromene core retains pharmacophore properties while being readily available synthetically.

An Inverse Electron Demand Azo-Diels-Alder Reaction of o-Quinone Methides and Imino Ethers: Synthesis of Benzocondensed 1,3-Oxazines.

We have studied the reactions of o-quinone methide precursors with imino ethers. The reaction provides a versatile route to substituted 1,3-benzoxazines. The proposed reaction mechanism involves the generation of the o-quinone methide intermediates, imino-Diels-Alder reaction, and elimination.

Synthesis and biological evaluation of 2-acylbenzofuranes as novel α-glucosidase inhibitors with hypoglycemic activity.

A series of benzofuran derivatives was synthesized as analogues of known natural α-glucosidase inhibitors. Their activity was evaluated in enzymatic assay and in rat model of diabetes mellitus. Newly identified inhibitors demonstrate significant potency with IC values ranging from 6.

Reaction of Push-Pull Enaminoketones and in Situ Generated ortho-Quinone Methides: Synthesis of 3-Acyl-4H-chromenes and 2-Acyl-1H-benzo[f]chromenes as Precursors for Hydroxybenzylated Heterocycles.

A simple and efficient method for the synthesis of 4H-chromenes and 1H-benzo[f]chromenes containing a trifluoroacetyl or aroyl group in the pyran ring from o-quinone methide precursors and push-pull enaminoketones has been developed. The chromenes are presumably formed through an initial oxa-Diels-Alder reaction, followed by an elimination of amine. The possibility of further transformations of given chromenes to o-hydroxybenzylated pyrazoles, isoxazoles, and pyridines has been demonstrated.

Potassium trinitromethanide as a 1,1-ambiphilic synthon equivalent: access to 2-nitroarenofurans.

The first example of the use of potassium trinitromethanide as a 1,1-ambiphilic synthon equivalent for the construction of a benzofuran moiety mediated by triethylamine has been developed. The method tolerates a variety of functional groups on the starting quaternary ammonium salt and has been successfully extended to polysubstituted benzofurans. Formation of an o-quinone methide intermediate is postulated as a key to the mechanism of this cascade process.

Reactions of o-quinone methides with pyridinium methylides: a diastereoselective synthesis of 1,2-dihydronaphtho[2,1-b]furans and 2,3-dihydrobenzofurans.

A simple, general route to the 1,2-dihydronaphtho[2,1-b]furans and 2,3-dihydrobenzofurans substituted at C-2 by an acyl or aryl group, starting from phenolic Mannich bases and pyridinium ylides, has been developed. The mechanism of the reaction is believed to involve the formation of the o-quinone methide intermediate, Michael-type addition of the ylide to the o-quinone methide, followed by intramolecular nucleophilic substitution.

2-(4-Meth-oxy-phen-yl)-4H-1,3,2-benzoxathia-phosphinine 2-sulfide.

The asymmetric unit of the title compound, C(14)H(13)O(2)PS(2), contains two crystallographically independent mol-ecules, which differ in the conformation of the 1,3,2-benzoxathia-phosphinine moieties (screw boat in the first mol-ecule and envelope in the second mol-ecule). In the crystal, neither classical nor non-classical hydrogen bonds are found. Weak inter-actions (about 2.