α-Amido sulphones as useful intermediates in the preparation of C-chiral α-aminophosphonates and α-aminophosphonic acids.

α-Amido sulphones have been used as useful starting materials in the preparation of C-chiral α-aminophosphonates and α-aminophosphonic acids. The developed methodology is based on a one-pot, base-catalysed in situ generation of an imine intermediate followed by addition of a phosphorus nucleophile. The presented protocol is simple and effective and can be applied to a variety of structurally diverse α-amido sulphones and phosphorus nucleophiles, leading to the desired pure products after simple crystallization in very good yields. Importantly, the use of H-phosphonate bearing a chiral auxiliary allows the reaction to be performed with high diastereoselectivity (a single diastereoisomer is generated and isolated) and the possibility of precise control of the configuration at the newly generated C-chiral centre.

Deamination of 1-Aminoalkylphosphonic Acids: Reaction Intermediates and Selectivity.

Deamination of 1-aminoalkylphosphonic acids in the reaction with HNO2 (generated "in situ" from NaNO2) yields a mixture of substitution products (1-hydroxyalkylphosphonic acids), elimination products (vinylphosphonic acid derivatives), rearrangement and substitution products (2-hydroxylkylphosphonic acids) as well as H3PO4. The variety of formed reaction products suggests that 1-phosphonoalkylium ions may be intermediates in such deamination reactions.

Green and Effective Preparation of α-Hydroxyphosphonates by Ecocatalysis.

A green and effective approach for the synthesis of structurally diversed α-hydroxyphosphonates via hydrophosphonylation of aldehydes under solventless conditions and promoted by biosourced catalysts, called ecocatalysts "Eco-MgZnOx" is presented. Ecocatalysts were prepared from Zn-hyperaccumulating plant species Arabidopsis halleri, with simple and benign thermal treatment of leaves rich in Zn, and without any further chemical treatment. The elemental composition and structure of Eco-MgZnOx were characterized by MP-AES, XRPD, HRTEM, and STEM-EDX techniques. These analyses revealed a natural richness in two unusual and valuable mixed zinc-magnesium and iron-magnesium oxides. The ecocatalysts were employed in this study to demonstrate their potential use in hydrophosphonylation of aldehydes, leading to various α-hydroxyphosphonate derivatives, which are critical building blocks in the modern chemical industry. Computational chemistry was performed to help discriminate the role of some of the constituents of the mixed oxide ecocatalysts. High conversions, broad substrate scope, mild reaction conditions, and easy purification of the final products together with simplicity of the preparation of the ecocatalysts are the major advantages of the presented protocol. Additionally, Eco-MgZnOx-P could be recovered and reused for up to five times.

Mechanochemistry and Eco-Bases for Sustainable Michael Addition Reactions.

The Michael addition reaction was revisited with a full focus on sustainability combined with efficiency, using mechanochemistry in mild conditions. First, the synthesis of cyclopentenone derivatives was chosen as a model reaction to find optimal conditions in mechanochemistry while using classical but weak bases. The reaction was efficient (84-95% yields), fast (2-6 h), solvent free, and required 0.1 equivalent of base. Aiming to reach greener conditions, classical bases were then replaced using new bio-sourced bases, called Eco-bases, that were easily prepared from plants and led to heterogeneous catalysts. The composition and structure of Eco-bases were characterized by MP-AES, XRPD, EBSD/EDS, HRTEM/EDX and ion chromatography. Interestingly, a high ratio of potassium was observed with the presence of K2Ca(CO3)2 for the most effective Eco-base. The new Eco-bases were used for the mechanical-assisted construction of functionalized alkenone derivatives. The versatility of the method has been successfully applied with good to excellent yields to different Michael donors and acceptors. Eco-bases were recycled and reused four times with the same performances. Combining Eco-bases and mechanochemistry in Michael addition reactions allowed reaching a maximum degree of sustainability (efficient, rapid, low catalyst loading, solvent-free reactions with bio-sourced catalysts) and participating in the development of mechanochemistry in sustainable chemistry.

SERS/TERS Characterization of New Potential Therapeutics: The Influence of Positional Isomerism, Interface Type, Oxidation State of Copper, and Incubation Time on Adsorption on the Surface of Copper(I) and (II) Oxide Nanoparticles.

The aim of this study was to investigate how the oxidation state of copper (Cu(I) vs Cu(II)), the nature of the interface (solid/aqueous vs solid/air), positional isomerism, and incubation time affect the functionalization of the surface of copper oxide nanostructures by [(butylamino)(pyridine)methyl]phenylphosphinic acid (PyPA). For this purpose, 2-, 3-, and 4-isomers of PyPA and the nanostructures were synthesized. The nanostructure were characterized by UV-visible spectroscopy (UV-vis), scanning electron microscopy (SEM), Raman spectroscopy (RS), and X-ray diffraction (XRD) analysis, which proved the formation of spherical Cu2O nanoparticles (Cu2ONPs; 1500-600 nm) and leaf-like CuO nanostructures (CuONSs; 80-180/400-700 nm, width/length). PyPA isomers were deposited on the surface of NSs, and adsorption was investigated by surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS). The changes of adsorption on the surface of copper oxide NSs caused by the above-mentioned factors were described and the enhancement factor on this substrate was calculated.

Synthesis and stability of 1-aminoalkylphosphonic acid quaternary ammonium salts.

An effective protocol for the quaternization of simple 1-aminoalkylphosphonic acids under basic conditions using Me2SO4 as a convenient alkylating agent is reported. During the course of the reaction, phosphonic acid quaternary ammonium derivatives, along with their corresponding monoesters are formed. Subsequent direct acidic hydrolysis of the crude reaction mixture leads to the desired novel N,N,N-trialkyl-N-(1-phosphonoalkyl)ammonium salts with overall yields of up to 88%. The developed protocol is general in scope and the products are purified by simple crystallization to give stable solids. Novel quaternary ammonium salts bearing a phosphonic group are generally unreactive in acidic and alkaline media. However, some of them undergo Hofmann elimination and substitution reactions in the presence of a base.

Phosphonates enantiomers receiving with fungal enzymatic systems.

BACKGROUND: Phosphonates derivatives are in the area of interests because of their unique chemical-physical features. These compounds manifest variety of biological interactions within the sensitive living cells, including impact on particular enzymes activities. Biological "cause and effect" interactions are based upon the specific matching between the structures and/or compounds and this is usually the result of proper optical configurations of particular chiral moieties. Presented research is targeted to the phosphonates with the heteroatom incorporated in their side functionalities. Such molecules are described as possible substrates of bioconversion for the first time lately and this field is not fully explored. RESULTS: Presented research is targeted to the synthesis of pure hetero-phosphonates enantiomers. The catalytic activity of yeasts and moulds were tested towards two substrates: the thienyl and imidazole phosphonates to resolve their racemic mixtures. Biotransformations conditions differed depending on the outcome, what included changing of following parameters: type of cultivation media, bioprocess duration (24-72 h), additional biocatalyst pre-treatment (24-48 h starvation step triggering the secondary metabolism). (S)-1-amino-1-(3-thienyl)methylphosphonate was produced with the assistance of R. mucilaginosa or A. niger (e.e. up to 98% and yield up to 100%), starting from the 3 mM of substrate racemic mixture. Bioconversion of racemic mixture of 3 mM of (1-amino-1-(4-imidazole)methylphosphonic acid) resulted in the synthesis of S-isomer (up to 95% of e.e.; 100% of yield) with assistance of R. mucilaginosa. 24 h biotransformation was conducted with biomass preincubated under 48-hour starvation conditions. Such stereoselective resolution of the racemic mixtures of substrates undergoes under kinetic control with the conversion of one from the enantiomers. CONCLUSIONS: Composition of the culturing media and pre-incubation in conditions of nutrient deficiency were significant factors influencing the results of kinetic resolution of racemic mixtures of phosphonic substrates and influencing the economic side of the biocatalysis e.g. by determining the duration of whole biocatalytic process.

Asymmetric synthesis of organophosphorus compounds using H-P reagents derived from chiral alcohols.

Chiral organophosphorus compounds, especially those containing C-stereogenic carbons in the proximity of the phosphorus atom, are known for their unique properties and have found wide applications that span from medicinal chemistry to enantioselective catalysis. However, the synthesis of such chiral molecules, especially with the precise control of stereochemistry at chiral carbon atoms, still remains a very challenging task. This review summarizes recent advances in the highly stereoselective formation of C- and, in some cases, also P-stereogenic organophosphorus compounds. The presented synthesis strategy is based on the use of H-P reagents bearing TADDOL, BINOL or a menthol moiety attached to the phosphorus atom and serving as a chiral auxiliary. Reactions of such chiral H-P species with different partners, e.g., alkenes, alkynes, imines, and carbonyl compounds, leading to structurally diverse chiral organophosphorus compounds with up to five chiral centers are comprehensively discussed. In each case, the stereochemical outcome of the reaction is influenced by the presence of the chiral alcohol used; therefore, the content of this review is compiled into sections with respect to the type of chiral alcohol attached to the phosphorus atom in the H-P species applied.

(S)-Thienyl and (R)-Pirydyl phosphonate Derivatives Synthesized by Stereoselective Resolution of Their Racemic Mixtures With Rhodotorula mucilaginosa (DSM 70403) - Scaling Approaches.

Rhodotorula mucilaginosa was successfully applied as a biocatalyst for the enantioselective resolution of the racemic mixtures of heteroatom phosphonates derivatives, resulting in receiving the following enantiomers: (S)-1-amino-1(2-thienyl)methylphosphonic acid (Product 1) and (R)-1-amino-1-(3'pirydyl) methylphosphonic acid (Product 2). Biological synthesis of both products is reported for the first time. Pure (S)-1-amino-1-(2-thienyl)methylphosphonic acid (Product 1) was isolated with a conversion degree of 50% after 24 h of biotransformation was conducted on a laboratory scale under moderate conditions (1.55 mM of substrate 1, 100 mL of distilled water, 135 rpm, 25°C; Method A). The scale was enlarged to semi-preparative one, using a simplified flow-reactor (Method C; 3.10 mM of substrate 1) and immobilized biocatalyst. The product was isolated with a conversion degree of 50% just after 4 h of biotransformation. Amino-1-(3'pirydyl)methylphosphonic acid (Substrate 2) was converted according to novel procedure, by the immobilized biocatalyst - Rhodotorula mucilaginosa. The process was carried out under moderate conditions (3.19 mM - substrate 2 solution; Method C1) with the application of a simplified flow reactor system, packed with the yeasts biomass entrapped in 4% agar-agar solution. Pure (R)-amino-1-(3'pirydyl)methylphosphonic (50% of conversion degree) was received within only 48 h.

An approach to new chiral bicyclic imines and amines via Horner-Wadsworth-Emmons reaction.

New chiral bicyclic imines, enamines and amines were prepared via Horner-Wadsworth-Emmons reaction of hexahydroquinoxalin-2(1H)-one-derived phosphonate, as the source of a phosphonate carbanion, and a wide range of structurally diverse carbonyl substrates. The simplicity of the synthetic protocol, high selectivity, and broad substrate scope are the main advantages of the presented methodology.

Aminophosphonates and aminophosphonic acids with tetrasubstituted stereogenic center: diastereoselective synthesis from cyclic ketimines.

New chiral tetrasubstituted aminophosphonic acid derivatives of hexahydroquinoxalin-2(1H)-one were synthesised via highly diastereoselective hydrophosphonylation of the corresponding imines with tris(trimethylsilyl) phosphite as phosphorus nucleophile. High asymmetric induction, good yields, mild reaction conditions, and ease of purification of the final products are the key advantages of the presented protocol.

Depollution of mining effluents: innovative mobilization of plant resources.

Based on the ability of some specific aquatic plants to concentrate metals in their roots, we propose an innovative biosorption system to clean up mining effluents. The system we propose represents an interesting solution to an important environmental problem, the decontamination of metal-polluted water and prevention of dispersal of metals into the environment. The solution presented is a form of ecological recycling of Zn, an essential primary metal in many industrial applications. Finally, the methodology developed is a sustainable way of managing the biomass from eradication or control of invasive plants.

Phosphonic and Phosphinic Acid Derivatives as Novel Tyrosinase Inhibitors: Kinetic Studies and Molecular Docking.

A dozen of phosphonic and phosphinic acid derivatives containing pyridine moiety were synthesized and its inhibitory activity toward mushroom tyrosinase was investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. All the compounds (1-10) demonstrated the inhibitory effect with the IC50 and inhibition constants ranging millimolar concentrations. The obtained results indicate that the compounds show different types of inhibition (competitive, noncompetitive, mixed), but all of them are reversible inhibitors. The obtained outcomes allowed to make the structure-activity relationship (SAR) analysis. Compound 4 ([(benzylamino)(pyridin-2-yl)methyl]phenylphosphinic acid) revealed the lowest IC50 value of 0.3 mm and inhibitory constant of Ki 0.076 mm, with noncompetitive type and reversible mechanism of inhibition. According to SAR analysis, introducing bulky phenyl moieties to phosphonic and amino groups plays an important role in the inhibitory potency on activity of mushroom tyrosinase and could be useful in design and development of a new class of potent organophosphorus inhibitors of tyrosinase. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties. They may have broad application in food industry and cosmetology.

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation.

The influence of microwave and ultrasonic irradiation on the performance of ammonium-tagged Ru-based catalysts in olefin metathesis transformations in aqueous media was studied. Differences in the catalytic activity in correlation with the nature of the present counter ion and the size of the N-heterocyclic carbene (NHC) ligand were revealed. The presented methodology allows for preparation of a variety of polar and non-polar metathesis products under environmentally friendly conditions.

First biological conversion of chiral heterophosphonate derivative - Scaling and paths of conversion discussion.

Presented work describes the first approach for the biocatalytic resolution of racemic mixtures of heterophosphonate derivative. Penicillium funiculosum and Rhodotorula mucilaginosa were successfully applied for the biological conversion of racemic mixture of 1-amino-1-(3'-pyridyl)methylphosphonic acid 3. Both microorganisms carried out the kinetically driven process leading to conversion of one from the substrate enantiomers, leaving the second one unreacted. Application of R. mucilaginosa allowed obtaining pure enantiomer of the substrate (yield 100%, e.e 100% - unreacted isomer) after 24 h of biotransformation of 3 in the laboratory scale process (Method E), applying biocatalyst pre-treatment step - 24 h of starvation. In case of other biocatalyst, application of whole cells of P. funiculosum in laboratory scale process, also resulted in conversion of the racemic mixture of substrate 3via oxidative deamination into ketone derivative, which was then bioreduced (second step of the process) into 1-hydroxy-1-(3'-pyridyl)methylphosphonic acid 4. This time two products were isolated: unreacted substrate and hydroxy compound 4. Conversion degree ranged from 30% (standard procedure, method A) to even 70% (with extra addition of sodium pyruvate - method B2). However, in this case, bioconversion was not enantioselective - products: amino- and hydroxyderivative were obtained as racemic mixtures. Both biocatalysts were also tested towards the scaling so other biocatalytic procedures were introduced - with immobilized fungal mycelium. In case of Rhodotorula mucilaginosa this approach failed (data not shown) but Penicillium funiculosum turned out to be active and also selective. Thus, application of this biocatalyst in the half-preparative scale, continuous-flow bioprocess (Method C2) resulted in the obtaining of pure S-3 (100% e.e.) isomer with the 100% of conversion degree, without any side products. Recorded NMR spectra allowed confirming the reaction progress and its selectivity and also postulating possible mechanism of conversion.

2-Azanorbornane--a versatile chiral aza-Diels-Alder cycloadduct: preparation, applications in stereoselective synthesis and biological activity.

The review presents the achievements in the field of preparation of chiral 2-azanorbornyl derivatives and their application in various stereoselective reactions as well as in biomimetic studies.

From biodiversity to catalytic diversity: how to control the reaction mechanism by the nature of metallophytes.

Phytoextraction is widely used for the reclamation of degraded sites, particularly to remove trace metals from contaminated soils. Whereas this technique demonstrates several advantages, the biomass resulting from phytoextraction processes is highly enriched in metallic elements and constitutes therefore a problematic waste. We show here that this biomass can be used for the preparation of novel polymetallic extracts, with high potential as catalysts or reagents in organic synthesis. This new concept of ecocatalysis constitutes an innovative recycling of metallic elements whose current known reserves could be exhausted in the coming decades. The ecocatalysts Eco-Zn and Eco-Ni prepared respectively from Zn and Ni hyperaccumulating plants display two distinct chemical reactivities, starting from the same substrates. Eco-Zn led to the formation of esters of commercial interest for the fragrance industry, following a hydro-acyloxy-addition reaction pathway. In contrast, Eco-Ni afforded chlorinated products thank to the hydrochlorination of alkenes. Both ecocatalysts allowed the synthesis of valuable products in high yields through methodologies in line with the spirit of sustainable chemistry.

Biosourced polymetallic catalysts: an efficient means to synthesize underexploited platform molecules from carbohydrates.

Polymetallic hyperaccumulating plants growing on wastes from former mining activity were used as the starting material in the preparation of novel plant-based Lewis acid catalysts. The preparation of biosourced Lewis acid catalysts is a new way to make use of mining wastes. These catalysts were characterized by X-ray fluorescence, X-ray diffraction, inductively coupled plasma mass spectrometry, and direct infusion electrospray ionization mass spectrometry. These analyses revealed a complex composition of metal species, present mainly as polymetallic chlorides. The catalysts proved to be efficient and recyclable in a solid-state version of the Garcia Gonzalez reaction, which has been underexploited until now in efforts to use carbohydrates from biomass. This methodology was extended to various carbohydrates to obtain the corresponding polyhydroxyalkyl furans in 38-98% yield. These plant-based catalysts may be a better alternative to classical Lewis acid catalysts that were previously used for the Garcia Gonzalez reaction, such as ZnCl2 , FeCl3 , and CeCl3 , which are often unrecyclable, require aqueous treatments, or rely on metals, the current known reserves of which will be consumed in the coming decades. Moreover, the plant-based catalysts allowed novel control of the Garcia Gonzalez reaction, as two different products were obtained depending on the reaction conditions.

Raman, surface-enhanced Raman, and density functional theory characterization of (diphenylphosphoryl)(pyridin-2-, -3-, and -4-yl)methanol.

This work presents near-infrared Raman spectroscopy (FT-RS) and surface-enhanced Raman scattering (SERS) studies of three pyridine-α-hydroxymethyl biphenyl phosphine oxide isomers: (diphenylphosphoryl)(pyridin-2-yl)methanol (α-Py), (diphenylphosphoryl)(pyridin-3-yl)methanol (ß-Py), and (diphenylphosphoryl)(pyridin-4-yl)methanol (γ-Py) adsorbed onto colloidal and roughened in oxidation-reduction cycles silver surfaces. The molecular geometries in the equilibrium state and vibrational frequencies were calculated by density functional theory (DFT) at the B3LYP 6-311G(df,p) level of theory. The results imply that the most stable structure of the investigated molecules is a dimer created by two intermolecular hydrogen bonds between the H atom of the α-hydroxyl group (in up (HOU) or down (HOD) stereo bonds position) and the O atom of tertiary phosphine oxide (═O) of the two monomers. Comparison the FT-RS spectra with the respective SERS spectra allowed us to predict the orientation of the hydroxyphosphonate derivatives of pyridine that depends upon both the position of the substituent relative to the ring N atom (in α-, ß-, and γ-position, respectively) and the type of silver substrate.

Diastereoselective hydrophosphonylation of imines using (R,R)-TADDOL phosphite. Asymmetric synthesis of alpha-aminophosphonic acid derivatives.

Efficient synthesis of alpha-aminophosphonic acid derivatives is achieved, the key step being a diastereoselective hydrophosphonylation of N-diphenylphosphinyl imines using a readily available chiral cyclic (R,R)-TADDOL-phosphite derived from inexpensive natural tartaric acid.