Stereoselective inverse conjugate addition of nitrogen and carbon nucleophiles to allenyl phosphine oxide. Synthesis of α,β-unsaturated phosphine oxides

Issue in Honor of Prof. Paweł Kafarski[EN] The reactivity of new three carbon synthon, generated in situ from the reaction of electrondeficient allenes with an appropriate phosphine as the catalyst, toward pronucleophilic reagents is described. Triphenylphosphine-catalyzed reaction of allenes derived from phosphine oxides with nitrogen- or carbonucleophiles gave the γ-addition product as a mixture of cis and trans isomers

Sc(OTf)(3)-Mediated [4+2] Annulations of N-Carbonyl Aryldiazenes with Cyclopentadiene to Construct Cinnoline Derivatives: Azo-Povarov Reaction

We disclose the first accomplishment of the azo-Povarov reaction involving Sc(OTf)3-catalyzed [4 + 2] annulations of N-carbonyl aryldiazenes with cyclopentadiene in chloroform, in which N-carbonyl aryldiazenes act as 4π-electron donors. Hence, this protocol offers a rapid access to an array of cinnoline derivatives in moderate to good yields for substrates over a wide scope. The synthetic potential of the protocol was achieved by the gram-scale reaction and further derivatization of the obtained polycyclic product.Financial support by the Ministerio de Ciencia, Innovacion y Universidades (MCIU), Agencia Estatal de Investigacion (AEI) y Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-101818-B-I00, UE), and Gobierno Vasco (GV, IT 992-16) is gratefully acknowledged. X.J.-A. thanks the Basque Country Government for the granted predoctoral fellowship. The authors thank technical and human support provided by SGIker (UPV/EHU/ERDF, EU)

The Intramolecular Povarov Tool in the Construction of Fused Nitrogen-Containing Heterocycles

Nitrogen heterocycles are part of the structure of natural products and agents with important biological activity, such as antiviral, antibiotic, and antitumor drugs. For this reason, heterocyclic compounds are one of today’s most desirable synthetic targets and the Povarov reaction is a powerful synthetic tool for the construction of highly functionalized heterocyclic systems. This process involves an aromatic amine, a carbonyl compound, and an olefin or acetylene to give rise to the formation of a nitrogen-containing heterocycle. This review illustrates advances in the synthetic aspects of the intramolecular Povarov reaction for the construction of intricate nitrogen-containing polyheterocyclic compounds. This original review presents research done in this field, with references to important works by internationally relevant research groups on this current topic, covering the literature from 1992 to 2022. The intramolecular Povarov reactions are described here according to the key processes involved, using different combinations of aromatic or heteroaromatic amines, and aliphatic, aromatic, or heteroaromatic aldehydes. Some catalytic reactions promoted by transition metals are detailed, as well as the oxidative Povarov reaction and some asymmetric intramolecular Povarov processes.Financial support from the Ministerio de Ciencia, Innovación y Universidades (MCIU) (PID2021-122558OB-I00, UE), by Gobierno Vasco, Universidad del País Vasco (GV, IT1701- 22; UPV) and by Fundación Vital (VITAL21/01) is gratefully acknowledged. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Natur

Phosphorus substituted hydroxylamine and hydroxamic acid derivatives: synthesis and reactivity

Dedicated to Prof. Julio Alvarez-Builla on the occasion of his 65th anniversary.[EN] This review summarizes several reports concerning the synthesis and synthetic applications of hydroxylamines derived from phosphines, phosphine oxides and phosphonates, and phosphorus substituted hydroxamic acid derivatives. The first section outlines the synthesis and reactivity of phosphorus O-substituted and N-substituted hydroxylamines as well as several transformations of phosphorus substituted hydroxylamines including: rearrangement, hydrolysis, reduction and oxidation reactions. The second part of the review covers the synthesis and reactivity of phosphorus O-, N-, and C-substituted hydroxamic acid derivatives

Synthesis and Antiproliferative Activity of Phosphorus Substituted 4-Cyanooxazolines, 2-Aminocyanooxazolines, 2-Iminocyanooxazolidines and 2-Aminocyanothiazolines by Rearrangement of Cyanoaziridines

Several phosphorus-substituted N-acylated cyanoaziridines 2 and N-carbamoylated cyanoziridines 5 were prepared in good to high yields. N-Acylated cyanoaziridines 2 were used, after ring expansion, in an efficient synthesis of oxazoline derivative 3a and in a completely regio-controlled reaction in the presence of NaI. Conversely, N-carbamoyl cyanoaziridines 5 reacted with NaI to obtain a regioisomeric mixture of 2-aminocyanooxazolines 7. Mild acidic conditions can be used for the isomerization of N-thiocarbamoyl cyanoaziridine 6a into a 2-aminocyanothiazoline derivative 8a by using BF3·OEt2 as a Lewis acid. Likewise, a one pot reaction of NH-cyanoaziridines 1 with isocyanates obtained 2-iminocyanooxazolidines 9 regioselectively. This synthetic methodology involves the addition of isocyanates to starting cyanoaziridines to obtain N-carbamoyl cyanoaziridines 5, which after the ring opening, reacts with a second equivalent of isocyanate to give the final 2-imino cyanooxazolidines 9. In addition, the cytotoxic effect on the cell lines derived from human lung adenocarcinoma (A549) was also screened. 2-Iminooxazolidines 9 exhibited moderate activity against the A549 cell line in vitro. Furthermore, a selectivity towards cancer cells (A549) over non-malignant cells (MCR-5) was detected.Financial support by the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) y Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-101818-B-I00, UE), and Gobierno Vasco (GV), (IT 992-16) is gratefully acknowledged

Phosphinotripeptidic Inhibitors of Leucylaminopeptidases

Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate pseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is conveniently available from the three-component condensation of appropriate amino components, aldehydes, and hypophosphorous acid. One of the crucial synthetic steps is the careful selection of the protecting groups for all the functionals. Determination of the inhibitor activity of the obtained compounds has been done using UV-Vis spectroscopy and standard substrate L-Leu-p-nitroanilide toward the enzymes isolated from the porcine kidney (SsLAP, Sus scrofa Leucine aminopeptidase) and barley seeds (HvLAP, Hordeum vulgare Leucine aminopeptidase). An efficient procedure for the preparation of phosphinotripeptides has been performed. Activity test shown that introduction of additional residue into P2 position obtains the micromolar range inhibitors of SsLAP and HvLAP. Moreover, careful selection of the residue in the P2 position should improve its selectivity toward mammalian and plant leucyl aminopeptidases.This research was funded by the Polish Ministry of Science and Higher Education (PMSHE) for the Faculty of Chemistry of Wrocław University of Science and Technology and by Wroclaw Research Center EIT+ under the project “Biotechnologies and advanced medical technologies—BioMed”, grant number POIG 01.01.02-02-003/08-00, 00 financed from the European Regional Development Fund (Operational Programme Innovative Economy, 1.1.2. B. O. is recipient of a Ph.D. fellowship from a project funded by the European Social Found. Financial support by the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) y Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-101818-B-I00, UE), and Gobierno Vasco (GV), (IT 992-16) is gratefully acknowledged

Chiral self-recognition in a bispericyclic cyclodimerisation reaction of 1-azadienes

Hermaphroditism of molecules: as in nature some species behave as male or female depending on the environment, herein we report a bispericyclic dimerisation of cyclic 1-azadienes where a molecule can behave as either diene or dienophile, depending on its location at the transition state. In a symmetrical reactive complex, here represented by an arbitrary reference system, a molecule that is positioned on top acts as the diene unit, while the dienophile partner is the one situated at the bottom. In addition, a strong chiral self-recognition phenomenon is observed, where each enantiomer within a racemic mixture of chiral 1-azadienes exclusively recognises itself. In order to shed some light into the understanding of the chiral self-recognition effect, an extensive DFT study of the reaction pathway is provided, concluding that a combination of attractive π-stacking forces and repulsive steric interactions is at the origin of the high stereospecificity of the reaction.Financial support by Ministerio de Ciencia, Innovación y Universidades (MCIU-Madrid) (PID2021-122558OB-I00, UE), and Eusko Jaurlaritza (GV, IT1701-22 and IT-1553-22; UPV-EHU) is gratefully acknowledged. The authors are grateful for technical and human support provided by SGIker (UPV/EHU/ERDF, EU). The authors thank SGI/IZO-SGIker of the UPV/EHU and the DIPC for the generous allocation of analytical and computational resources. A. L.-F. thanks the Basque Country Government for a predoctoral grant

Assessing the Biofortification of Wheat Plants by Combining a Plant Growth-Promoting Rhizobacterium (PGPR) and Polymeric Fe-Nanoparticles: Allies or Enemies?

Biofortification has been widely used to increase mineral nutrients in staple foods, such as wheat (Triticum aestivum). In this study, a new approach has been used by analyzing the effect of inoculation with a plant growth-promoting rhizobacterium (PGPR), namely, Bacillus aryabhattai RSO25 and the addition of 1% (v/v) of organometallic Fe-containing polymeric nanoparticles (FeNPs) alone and in combination. Previously, the minimal inhibitory concentration of FeNPs for the bacterium was determined in order not to inhibit bacterial growth. All treatments had minor effects on seed germination and plant survival. Considering the physiology of plants, several photosynthetic parameters were significantly improved in individual treatments with FeNPs or the bacterium, particularly the efficiency of the photosystem II and the electron transport rate, which is indicative of a better photosynthetic performance. However, at the end of the experiment, a significant effect on final plant growth was not observed in shoots or in roots. When using FeNPs alone, earlier spike outgrow was observed and the final number of spikes increased by 20%. Concerning biofortification, FeNPs increased the concentration of Fe in spikes by 35%. In fact, the total amount of Fe per plant base rose to 215% with regard to the control. Besides, several side effects, such as increased Ca and decreased Na and Zn in spikes, were observed. Furthermore, the treatment with only bacteria decreased Na and Fe accumulation in grains, indicating its inconvenience. On its side, the combined treatment led to intermediate Fe accumulation in spikes, since an antagonist effect between RSO25 and FeNPs was observed. For this reason, the combined treatment was discouraged. In conclusion, of the three treatments tested, FeNPs alone is recommended for achieving efficient Fe biofortification in wheat.Ministry of Science and Innovation of Spain grant PID2019-109371GB-I00Junta de Andalucía (Spain) Project FQM-135University of Seville, Spain PPIT-2020/0000109

Correlation Analysis of People Attitude and the Development of Chemical Processes in the Human Body

This chemical science investigation was made to efficiently understand the way in which ionic substances operate in the human body and its correlation that they can have with the attitude of people, whose evaluation was carried out according to the analysis of three actions developed in the human body, such as digestion factors, family, work and social relationships (emotional actions) and the health of 10 people surveyed in the city of Tijuana, Baja California. This evaluation had a main hypothesis at the beginning of the investigation, indicating that, of the three factors mentioned, the one that links emotions had the greatest effect on the behavior of the people evaluated, with the aspect of family and work relationships being of primary importance; followed by the health factor and finally the digestion factor. This scientific study included an analysis of three principal aspects, being first the daily food as a nutrition action, followed a chemical analysis of ionic substances of the human body of the 10 persons evaluated. In addition, the third aspect evaluated was the emotional state of the people and a clinic with the urine analysis were considered to indicate the pH, temperature and oxygen level of each person, with which the main chemical elements of the ionic substances that can circulate through the human body were obtained, as part of the food intake. and drinks, emotional factor and digestion. This scientific study was made from March to May of 2023

Nanopartículas poliméricas de zinc y su potencial uso como agentes de biofortificación

En la actualidad el hambre y los malos hábitos alimenticios son un problema reconocido por la organización mundial de la salud (OMS). A pesar de todos los esfuerzos propuestos para solventar este problema, la OMS ha admitido que no se alcanzará el objetivo de hambre cero para 2030. Por todo esto y para aportar soluciones imaginativas a este problema, nos propusimos emplear nanopartículas poliméricas cargadas con zinc, junto con la bacteria Pantoea agglomerans, promotora de crecimiento de plantas (PGPR), para mejorar el valor nutricional de plantas como el trigo (Triticum aestivum), mediante bioforitficación. Las plantas de trigo fueron tratadas, tras su previa germinación, y se recogieron medidas de concentración de metales usando técnicas analíticas. Los resultados mostraron que los parámetros físicos y fisiológicos no se vieron afectados y se produjo una acumulación notoria del Zn en la parte aérea