CS2/KOH System-Promoted Stereoselective Synthesis of (E)-Alkenes from Diarylalkynes and a "Hidden" Zinin-Type Reduction of Nitroarenes into Arylamines.

In this work, we present the CS2/KOH system as a practical and efficient reductive medium for obtaining (E)-alkenes from alkynes through a highly stereoselective semireduction reaction. This cost-effective system enabled successful semireduction reactions of diverse alkynes using water as a hydrogen source, yielding moderate to excellent yields. The versatility of this protocol is further demonstrated through the synthesis of relevant compounds such as pinosylvin and resveratrol precursors, along with the notable anticancer agent DMU-212. Furthermore, during the reaction scope investigation, we serendipitously disclosed that this reductive system was also able to promote a Zinin-type reaction to reduce nitroarenes into arylamines.

Radical cyclization of alkynyl aryl ketones for the synthesis of 3-seleno-substituted thiochromones and chromones.

We report a strategy for the direct synthesis of 3-organylselanylthiochromones and 3-organylselanylchromones via the radical cyclization reaction between alkynyl aryl ketones containing an ortho-thiopropyl/methoxy group and diorganyl diselenides promoted by Oxone®. This method allows the construction and seleno-functionalization of thiochromones and chromones using Oxone® as a stable and non-hazardous oxidizing agent in the presence of CH3CN at 82 °C. These reactions tolerate a variety of substituents, and allowed the synthesis of twenty-one new 3-organylselanylthiochromones and selanylchromones in good to excellent yields (55-95%). Additionally, the developed method proved to be suitable for scale up (3.0 mmol, 80%), and the synthetic usefulness of the prepared compounds was demonstrated in the oxidation of 2-phenyl-3-(phenylselanyl)-4H-thiochromen-4-one.

Synthesis of Seleno-Dibenzocycloheptenones/Spiro[5.5]Trienones by Radical Cyclization of Biaryl Ynones.

We report herein an alternative method for the synthesis of seleno-dibenzocycloheptenones and seleno-spiro[5.5]trienones through the radical cyclization of biaryl ynones in the presence of diorganyl diselenides, using Oxone as a green oxidizing agent. The reactions were conducted using acetonitrile as the solvent in a sealed tube at 100 °C. The protocol is operationally simple and scalable, exhibits high regioselectivity, and allows the synthesis of 24 dibenzocycloheptenones/spiro[5.5]trienones in yields of up to 99%, 17 of which are unpublished compounds. Additionally, synthetic transformations of the prepared compounds, such as oxidation and reduction reactions, are demonstrated.

UVA Light-promoted Catalyst-free Cyclization of Vinyl Selenides: Green and Efficient Synthesis of C3-Unsubstituted 2-Selanyl Benzochalcogenophenes.

A metal- and catalyst-free photo-promoted cyclization of properly substituted vinyl selenides was developed using UVA irradiation. A total of eighteen new C3-unsubstituted 2-selanyl benzochalcogenophenes (benzofurans, benzothiophenes and benzoselenophenes) were prepared in 30-86% yield after irradiation with UVA at room temperature. The usefulness of the title compounds was demonstrated in the easy functionalization of the remaining free C-H bond of the benzochalcogenophenes to form new C-Se and C-Br bonds by simple procedures. Furthermore, the reaction can be performed under natural sunlight irradiation and the solvent is easily reused further in several subsequent runs.

Recent Advances in the Synthesis of Selenophenes and Their Derivatives.

The selenophene derivatives are an important class of selenium-based heterocyclics. These compounds play an important role in prospecting new drugs, as well as in the development of new light-emitting materials. During the last years, several methods have been emerging to access the selenophene scaffold, employing a diversity of cyclization-based synthetic strategies, involving specific reaction partners and particularities. This review presents a comprehensive discussion on the recent advances in the synthesis of selenophene-based compounds, starting from different precursors, highlighting the main differences, the advantages, and limitations among them.

Synthesis of 2-Organylchalcogenopheno[2,3-b]pyridines from Elemental Chalcogen and NaBH4 /PEG-400 as a Reducing System: Antioxidant and Antinociceptive Properties.

An alternative method to prepare 2-organylchalcogenopheno[2,3-b]pyridines was developed by the insertion of chalcogen species (selenium, sulfur or tellurium), generated in situ, into 2-chloro-3-(organylethynyl)pyridines by using the NaBH4 /PEG-400 reducing system, followed by an intramolecular cyclization. It was possible to obtain a series of compounds with up to 93 % yield in short reaction times. Among the synthesized products, 2-organyltelluropheno[2,3-b]pyridines have not been described in the literature so far. Moreover, the compounds 2-phenylthieno[2,3-b]pyridine (3 b) and 2-phenyltelluropheno[2,3-b]pyridine (3 c) exhibited significant antioxidant potential in different in vitro assays. Further studies demonstrated that compound 3 b exerted an antinociceptive effect in acute inflammatory and non-inflammatory pain models, thus indicating the involvement of the central and peripheral nervous systems on its pharmacological action. More specifically, our results suggest that the intrinsic antioxidant property of compound 3 b might contribute to attenuating the nociception and inflammatory process on local injury induced by complete Freund's adjuvant (CFA).

Modulation of COX-2, INF-É£, glutamatergic and opioid systems contributes to antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide.

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies.

Ultrasound-Promoted One-Pot Synthesis of Mono- or Bis-Substituted Organylselanyl Pyrroles.

A simple method for the direct mono- and bis-organylselenylation of N-substituted pyrroles through a multicomponent reaction promoted by ultrasonic radiation was described. These sonochemical promoted reactions were performed between different primary amines, 2,5-hexanedione and dialkyl, diheteroaryl, or diaryl diselenides, using catalytic amounts of copper iodide. Depending on the amount of copper iodide and diorganyl diselenide used in the reactions, mono- or bis-organylselenylation products were efficiently synthesized in high yields.

Synthesis and Pharmacological Evaluation of Novel Selenoethers Glycerol Derivatives for the Treatment of Pain and Inflammation: Involvement of Nitrergic and Glutamatergic Systems.

In the present study, the synthesis of new selenoethers from nucleophilic substitution reaction between organyl halides and nucleophilic species of selenium generated in situ was demonstrated. After, this method was applied for the synthesis of pyridylselenides glycerol derivatives 9b and 9c and the antinociceptive and anti-inflammatory effects, as well as, acute toxicity were evaluated. In the formalin test, the compound 9b caused a reduction in licking time in both phases. Compounds 9b and 9c increased the latency to response in the hot-plate test and reduced the licking time induced by glutamate. Our results revealed the involvement of the nitrergic and/or glutamatergic pathways in the antinociceptive action of the compounds. Additionally, 9b and 9c did not cause any toxicity signals and oxidative stress parameters were not modified by treatments. Here, it was developed an alternative and efficient method for the synthesis of selenoethers glycerol derivatives. Furthermore, we demonstrated that this class is indeed interesting for the research of new drugs. Graphical Abstract ᅟ.