A significant number of important acyl-transfer reactions, such as direct acylation, ortho acylation, heteroatom acylation, and a diversity of cyclization reactions using the title compound as a key starting material, have been described in recent years. Just like a sleeping beauty, α-oxocarboxylic acids were awakened from a 17-year sleep to become important reagents in classical and new acylation reactions. The greener characteristic of the coproduct formed in reactions using α-keto acid (only CO 2 ), together with its versatility as a building block in catalytic organic synthesis, accredit it as a candidate to green acylating agent, an alternative to acyl chloride, and other acyl-transfer reagents. This review presents the impressive breakthroughs achieved mainly in the past decade in the development of new catalytic reactions for the formation of C−C, C−N, and C−S bonds using α-keto acids. CONTENTS 1. Introduction 7113 2. Classical Methods and Recent Advances in the Synthesis of α-Keto Acids 7115 2.1. Physical Properties of α-Keto Acids 7119 3. α-Keto Acids in Acylation Reactions 7119 3.1.
The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 μM and 8 μM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile.
This review is dedicated to the memory of Prof. Nicola Petragnani, a pionner in the chemistry of selenium and tellurium in Brazil, who passed away on December 5, 2015.Organochalcogen compounds (containing S, Se and Te) are interesting either for use as an intermediate in the synthesis of complex molecules or for the exploitation of their biological properties. The growing in the number of papers on the synthesis and application of organochalcogen compounds has been accompanied by a concern about how they are prepared. Here, we provide a comprehensive and updated review on re-cent synthetic methods available for their synthesis using alternative solvents or solvent-free conditions and non-classical energy sources (microwaves irradiation, sonochemistry and mechanochemistry). Organized in fourteen sections, this review brings the more than one hundred alternative methods described so far to access organic compounds containing selenium, tellurium and sulfur.[a] Prof.
As imple and rapid methodf or the selective synthesis of 3-(organylselanyl)-1 H-indoles and3 -(organylselanyl)imidazo[1,2-a]pyridines catalyzed by CuI/SeO 2 under ultrasound irradiation was developed. This protocol employs adiverse range of 1 H-indoles or imidazo[1,2-a]pyridines and diorganyl diselenides to afford the corresponding products selectively in good to excellent yields. Moreover,t he antioxidant activity of these compounds was evaluated by using aw ider ange of in vitro assays,s uch as 2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1picrylhydrazyl (DPPH) radical, ferric ion reducing antioxidant power (FRAP), and inhibition of reactive speciesf ormation in mice cortex. The bioassays revealed thatb oth classes of the newly synthesized organoselenium compounds present antioxidanta ctivity,w ith emphasis on the 3-(organylselanyl)-1 Hindoles.T his pharmacological activity opens aw ide range of biological applications where the reduction of oxidative stress is essential.[a] B.
Results and DiscussionAc omparatives tudy on the use of microwaves, US, and conventional heating in the copper-catalyzed selenylation of indoles in DMSO was recently reported by us. [18b] In this reaction, Figure 1. 3-Arylselanylindoles A and B and 3-thioimidazo[1,2-a]pyridines C and D with similar effects to Combretastatin A-4a nd Enviroxime.Scheme1.Generalscheme of the present work.
We present here our results of the electrophilic cyclization reaction of (Z)-selenoenynes with different electrophiles such as I(2), ICl, PhSeBr, and PhSeCl. The cyclization reaction proceeded cleanly under mild reaction conditions, and 3-substituted selenophenes were formed in moderate to excellent yields. We observed that the nature of solvent and structure of (Z)-selenoenyne were important to the cyclization reaction. In addition, the obtained 3-iodoselenophenes were readily transformed to more complex products using a metal-halogen exchange reaction with n-BuLi and trapping the intermediate formed with aldehydes, furnishing the desired secondary alcohols in good yields. Conversely, using the palladium or copper catalyzed cross-coupling reactions with terminal alkynes or alkyl alcohols, we were able to convert 3-iodoselenophene to Sonogashira or Ullmann type products, respectively, in good yields.
Ultrasonic (US) irradiation was successfully used as an alternative energy source to prepare 3-selanylindoles through the direct selanylation of indoles with diorganyl diselenides using CuI (20 mol%) as catalyst and DMSO as the solvent. By using this US-promoted reaction, eleven 3-organylselanylindoles were prepared selectively and in good yields. A comparative study between the reactions under conventional heating, microwave and ultrasound irradiations was performed, and it was observed advantage in using US over the other heating systems.
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