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Background The availability of soil phosphorus (P) often limits the productivities of wet tropical lowland forests. Little is known, however, about the metabolomic profile of different chemical P compounds with potentially different uses and about the cycling of P and their variability across space under different tree species in highly diverse tropical rainforests. Results We hypothesised that the different strategies of the competing tree species to retranslocate, mineralise, mobilise, and take up P from the soil would promote distinct soil 31P profiles. We tested this hypothesis by performing a metabolomic analysis of the soils in two rainforests in French Guiana using 31P nuclear magnetic resonance (NMR). We analysed 31P NMR chemical shifts in soil solutions of model P compounds, including inorganic phosphates, orthophosphate mono- and diesters, phosphonates, and organic polyphosphates. The identity of the tree species (growing above the soil samples) explained > 53% of the total variance of the 31P NMR metabolomic profiles of the soils, suggesting species-specific ecological niches and/or species-specific interactions with the soil microbiome and soil trophic web structure and functionality determining the use and production of P compounds. Differences at regional and topographic levels also explained some part of the the total variance of the 31P NMR profiles, although less than the influence of the tree species. Multivariate analyses of soil 31P NMR metabolomics data indicated higher soil concentrations of P biomolecules involved in the active use of P (nucleic acids and molecules involved with energy and anabolism) in soils with lower concentrations of total soil P and higher concentrations of P-storing biomolecules in soils with higher concentrations of total P. Conclusions The results strongly suggest “niches” of soil P profiles associated with physical gradients, mostly topographic position, and with the specific distribution of species along this gradien

The surface chemistry of Metal-Organic Polyhedra (MOPs) is crucial to their physicochemical properties because it governs how they interact with external substances such as solvents, synthetic organic molecules, metal ions, and even biomolecules. Consequently, the advancement of synthetic methods that facilitate the incorporation of diverse functional groups onto MOP surfaces will significantly broaden the range of properties and potential applications for MOPs. This study describes the use of copper(I)-catalysed, azide-alkyne cycloaddition (CuAAC) click reactions to post-synthetically modify the surface of alkyne-functionalised cuboctahedral MOPs. To this end, a novel Rh(II)-based MOP with 24 available surface alkyne groups was synthesised. Each of the 24 alkyne groups on the surface of the "clickable" Rh-MOP can react with azide-containing molecules at room temperature, without compromising the integrity of the MOP. The wide substrate catalogue and orthogonal nature of CuAAC click chemistry was exploited to densely functionalise MOPs with diverse functional groups, including polymers, carboxylic and phosphonic acids, and even biotin moieties, which retained their recognition capabilities once anchored onto the surface of the MOP.

Homochiral 2-hydroxy-4-butyrolactone derivatives are important structural motifs frequently found in naturally occurring biologically active products, synthetic drugs, biodegradable polymers as well as building blocks and chiral auxiliaries in asymmetric organic synthesis (1). Among the methods described in the literature, the stereoselective reduction of 4-hydroxy-2-oxoacid derivatives to produce 2-hydroxy-4-butyrolactone derivatives remains unexplored. In this communication we report a tandem biocatalytic stereodivergent route for the preparation of these compounds using two stereocomplementary aldolases and oxidoreductases, using simple and achiral starting materials. The strategy comprises (Scheme 1) (i) aldol addition reaction of 2-oxoacids to formaldehyde using both 3-methyl-2-oxobutanoate hydroxymethyltransferase and 2-keto-3-deoxy-L-rhamnonate aldolase and variants thereof, and (ii) subsequent 2-oxogroup reduction of the aldol adduct by both ketopantoate reductase and a delta-1-piperidine-2-carboxylate/delta-1-pyrroline-2-carboxylate reductase with uncovered promiscuous ketoreductase activity. Finally, the formation of the corresponding lactone takes place during the work up and purification steps. Yields, enantiomeric excesses and diasteromeric ratios for a total of 23 structurally diverse 2-hydroxy-3-substituted-4-butyrolactones will be discussed. Moreover, one-pot one-step cascade reactions with the aldolases and reductases operating in tandem will be presented.

NAD(P)H-dependent ¿1-piperideine-2-carboxylate/¿1-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato (DpkAPsyrin, EC 1.5.1.21) catalyzes the stereoselective reduction of ¿1-piperideine-2-carboxylate and ¿1-pyrroline-2-carboxylate to L-pipecolic acid and L-proline respectively. Furthermore, DpkAPsyrin is also able to catalyze the enantioselective synthesis of N-methyl-L-amino acids from methylamine and various 2-oxo acids [1]. In our research group, we observed that in addition to the imine reductase activity, DpkAPsyrin have a promiscuous ketoreductase activity and, consequently, we consider interesting to exploit its underdeveloped synthetic capabilities for the synthesis of 2-hydroxy-4-arylbut-3-enoic acid (4). These 2-hydroxyacids are intermediates in the synthesis of 2-hydroxy-4-arylbutanoic acid, important building blocks for the production of a variety of angiotensin converting enzyme (ACE) inhibitors (e.g. enalapril, lisinopril, cilapril, and benazepril) [2]. In this communication we reported the preparation of structurally diverse (S)-2-hydroxy-4-arylbut-3-enoic acid (4) (isolated yield: 57%-78% and ee: 87%->99%) from aromatic aldehydes (1) and pyruvate (2) by enzymatic cascade reaction using trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida HBPAPputida) [3] and DpkAPsyrin (Scheme 1). The cascade process was possible because it was found that the ketoreductase preferentially reduced the aldol condensation adducts (3) rather than the pyruvate (2). This allows for high levels of 2-hydroxy-4-arylbut-3-enoic acids (4) conversions ( >95% after 24 h).

Water pollution threatens human and environmental health worldwide. Thus, there is a pressing need for new approaches to water purification. Herein, we report a novel supramolecular strategy based on the use of a metal-organic polyhedron (MOP) as a capture agent to remove nitrogenous organic micropollutants from water, even at very low concentrations (ppm), based exclusively on coordination chemistry at the external surface of the MOP. Specifically, we exploit the exohedral coordination positions of RhII-MOP to coordinatively sequester pollutants bearing N-donor atoms in aqueous solution, and then harness their exposed surface carboxyl groups to control their aqueous solubility through acid/base reactions. We validated this approach for removal of benzotriazole, benzothiazole, isoquinoline, and 1-napthylamine from water.

Productivity of tropical lowland moist forests is often limited by availability and functional allocation of phosphorus (P) that drives competition among tree species and becomes a key factor in determining forestall community diversity. We used non-target 31P-NMR metabolic profiling to study the foliar P-metabolism of trees of a French Guiana rainforest. The objective was to test the hypotheses that P-use is species-specific, and that species diversity relates to species P-use and concentrations of P-containing compounds, including inorganic phosphates, orthophosphate monoesters and diesters, phosphonates and organic polyphosphates. We found that tree species explained the 59% of variance in 31P-NMR metabolite profiling of leaves. A principal component analysis showed that tree species were separated along PC 1 and PC 2 of detected P-containing compounds, which represented a continuum going from high concentrations of metabolites related to non-active P and P-storage, low total P concentrations and high N:P ratios, to high concentrations of P-containing metabolites related to energy and anabolic metabolism, high total P concentrations and low N:P ratios. These results highlight the species-specific use of P and the existence of species-specific P-use niches that are driven by the distinct species-specific position in a continuum in the P-allocation from P-storage compounds to P-containing molecules related to energy and anabolic metabolism.

Productivity of tropical lowland moist forests is often limited by availability and functional allocation of phosphorus (P) that drives competition among tree species and becomes a key factor in determining forestall community diversity. We used non-target 31P-NMR metabolic profiling to study the foliar P-metabolism of trees of a French Guiana rainforest. The objective was to test the hypotheses that P-use is species-specific, and that species diversity relates to species P-use and concentrations of P-containing compounds, including inorganic phosphates, orthophosphate monoesters and diesters, phosphonates and organic polyphosphates. We found that tree species explained the 59% of variance in 31P-NMR metabolite profiling of leaves. A principal component analysis showed that tree species were separated along PC 1 and PC 2 of detected P-containing compounds, which represented a continuum going from high concentrations of metabolites related to non-active P and P-storage, low total P concentrations and high N:P ratios, to high concentrations of P-containing metabolites related to energy and anabolic metabolism, high total P concentrations and low N:P ratios. These results highlight the species-specific use of P and the existence of species-specific P-use niches that are driven by the distinct species-specific position in a continuum in the P-allocation from P-storage compounds to P-containing molecules related to energy and anabolic metabolism.

Productivity of tropical lowland moist forests is often limited by availability and functional allocation of phosphorus (P) that drives competition among tree species and becomes a key factor in determining forestall community diversity. We used non-target 31P-NMR metabolic profiling to study the foliar P-metabolism of trees of a French Guiana rainforest. The objective was to test the hypotheses that P-use is species-specific, and that species diversity relates to species P-use and concentrations of P-containing compounds, including inorganic phosphates, orthophosphate monoesters and diesters, phosphonates and organic polyphosphates. We found that tree species explained the 59% of variance in 31P-NMR metabolite profiling of leaves. A principal component analysis showed that tree species were separated along PC 1 and PC 2 of detected P-containing compounds, which represented a continuum going from high concentrations of metabolites related to non-active P and P-storage, low total P concentrations and high N:P ratios, to high concentrations of P-containing metabolites related to energy and anabolic metabolism, high total P concentrations and low N:P ratios. These results highlight the species-specific use of P and the existence of species-specific P-use niches that are driven by the distinct species-specific position in a continuum in the P-allocation from P-storage compounds to P-containing molecules related to energy and anabolic metabolism.

A new persistent organic free radical has been synthetized with Br atoms occupying the ortho‐ and para‐positions of a trityl core. After the isolation of its two propeller‐like atropisomers, Plus (P) and minus (M), their absolute configurations were assigned by a combination of theoretical and experimental data. Remarkably, no hints of racemization were observed up to 60 °C for more than two hours, due to the higher steric hindrance imposed by the bulky Br atoms. Therefore, when compared to its chlorinated homologue (t1/2=18 s at 60 °C), an outstanding stability against racemization was achieved. A circularly polarized luminescence (CPL) response of both enantiomers was detected. This free radical shows a satisfactory luminescent dissymmetry factor (|glum(592 nm)|≈0.7×10−3) despite its pure organic nature and low luminescence quantum yield (LQY). Improved organic magnetic CPL emitters derived from the reported structure can be envisaged thanks to the wide possibilities that Br atoms at para‐positions offer for further functionalization.

The congested nature of quaternary carbons hinders their preparation, most notably when stereocontrol is required. Here we report a biocatalytic method for the creation of quaternary carbon centers with broad substrate scope, leading to different compound classes bearing this structural feature. The key step comprises the aldol addition of 3,3-disubstituted 2-oxoacids to aldehydes catalyzed by metal dependent 3-methyl-2-oxobutanoate hydroxymethyltransferase from E. coli (KPHMT) and variants thereof. The 3,3,3-trisubstituted 2-oxoacids thus produced were converted into 2-oxolactones and 3-hydroxy acids and directly to ulosonic acid derivatives, all bearing gem-dialkyl, gem-cycloalkyl, and spirocyclic quaternary centers. In addition, some of these reactions use a single enantiomer from racemic nucleophiles to afford stereopure quaternary carbons. The notable substrate tolerance and stereocontrol of these enzymes are indicative of their potential for the synthesis of structurally intricate molecules.

3-Hydroxyisobutyric acid is an important intermediate in the biosynthesis of methacrylic acid. Its biocatalytic synthesis can be performed by aldolase-catalyzed aldol addition of propanal to formaldehyde followed by an enzymatic oxidation of the resulting 3-hydroxy-2-methylpropanal to 3-hydroxyisobutyric acid. In this work, D-fructose-6-phosphate aldolase D6Q variant was investigated as a key step for the biocatalytic preparation of 3-hydroxy-2-methylpropanal, a commercially unavailable precursor of 3-hydroxyisobutyric acid. The kinetic model of this step was developed for the purpose of reactor selection and process optimization. It was found that enzyme operational stability decay is co-dependent on the initial formaldehyde concentration. Thus, the choice of the initial conditions is crucial for a successful process set-up. It was concluded that fed-batch was the best reactor choice for this reaction due to enzyme inhibition by formaldehyde and propanal, and its operational stability decay. At the optimal process conditions, the product concentration, product yield, and volume productivity after 5.5 h were 72 g L−1, 88.5% and 313.7 g L−1 d−1, respectively. Enzymatic oxidation of 3-hydroxy-2-methylpropanal to the corresponding acid was performed as a proof of concept using an aldehyde dehydrogenase in the presence of NAD+, regenerated by water-forming NADH oxidase, and 2.5 g L−1 (24 mM) of 3-hydroxyisobutyric acid was obtained. © 2019 Institution of Chemical Engineers

Nitrogen heterocycles are structural motifs found in many bioactive natural products and of utmost importance in pharmaceutical drug development. In this work, a stereoselective synthesis of functionalized N-heterocycles was accomplished in two steps, comprising the biocatalytic aldol addition of ethanal and simple aliphatic ketones such as propanone, butanone, 3-pentanone, cyclobutanone, and cyclopentanone to N-Cbz-protected aminoaldehydes using engineered variants of d-fructose-6-phosphate aldolase from Escherichia coli (FSA) or 2-deoxy-d-ribose-5-phosphate aldolase from Thermotoga maritima (DERA Tma ) as catalysts. FSA catalyzed most of the additions of ketones while DERA Tma was restricted to ethanal and propanone. Subsequent treatment with hydrogen in the presence of palladium over charcoal, yielded low-level oxygenated N-heterocyclic derivatives of piperidine, pyrrolidine and N-bicyclic structures bearing fused cyclobutane and cyclopentane rings, with stereoselectivities of 96–98 ee and 97:3 dr in isolated yields ranging from 35 to 79%. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Asymmetric aldol addition of simple aldehydes and ketones to electrophiles is a cornerstone reaction for the synthesis of unusual sugars and chiral building blocks. We investigated D-fructose-6-phosphate aldolase from E. coli (FSA) D6X variants as catalysts for the aldol additions of linear and cyclic non-functionalized aliphatic ketones or ethanal as nucleophiles to non-phosphorylated hydroxyaldehydes. Thus, addition of propanone, cyclobutanone, cyclopentanone or ethanal to 3-hydroxypropanal or (S)- or (R)-3-hydroxybutanal catalyzed by FSA D6H and D6Q variants furnished rare deoxysugars in 8-77% isolated yields with high stereoselectivity (97:3 dr and >95% ee). © 2018 American Chemical Society.

4-Hydroxy-2-ketoacid derivatives are versatile building blocks for the synthesis of amino acids, hydroxy carboxylic acids and chiral aldehydes. Pyruvate aldolases are privileged catalysts for a straightforward access to this class of ketoacid compounds. In this work, a Class II pyruvate aldolase from Escherichia coli K-12, 2-keto-3-deoxy-L-rhamnonate aldolase (YfaU), was evaluated for the synthesis of amino acid derivatives of proline, pipecolic acid, and pyrrolizidine-3-carboxylic acid. The aldol addition of pyruvate to N-protected amino aldehydes was the key enzymatic aldol addition step followed by catalytic intramolecular reductive amination. The corresponding N-Cbz-amino-4-hydroxy-2-ketoacid (Cbz=benzyloxycarbonyl) precursors were obtained in 51%-95% isolated yields and enantioselectivity ratios from 26:74 to 95:5, with chiral -substituted N-Cbz-amino aldehydes. (S)-N-Cbz-amino aldehydes gave aldol adducts with preferentially (R)-configuration at the newly formed stereocenter, whereas the contrary is true for (R)-N-Cbz-amino aldehydes. Addition reactions to achiral amino aldehydes rendered racemic aldol adducts. Molecular models of the pre-reaction ternary complexes YfaU-pyruvate enolate-acceptor aldehyde were constructed to explain the observed stereochemical outcome of the reactions. Catalytic reductive amination of the aldol adducts yielded 4-hydroxy-2-pipecolic acid, and unprecedented C5 substituted 4-hydroxy proline and pyrrolizidine-3-carboxylic acid derivatives.

BackgroundThe phyllospheric microbiota is assumed to play a key role in the metabolism of host plants. Its role in determining the epiphytic and internal plant metabolome, however, remains to be investigated. We analyzed the Liquid Chromatography-Mass Spectrometry (LC-MS) profiles of the epiphytic and internal metabolomes of the leaves and flowers of Sambucus nigra with and without external antibiotic treatment application.ResultsThe epiphytic metabolism showed a degree of complexity similar to that of the plant organs. The suppression of microbial communities by topical applications of antibiotics had a greater impact on the epiphytic metabolome than on the internal metabolomes of the plant organs, although even the latter changed significantly both in leaves and flowers. The application of antibiotics decreased the concentration of lactate in both epiphytic and organ metabolomes, and the concentrations of citraconic acid, acetyl-CoA, isoleucine, and several secondary compounds such as terpenes and phenols in the epiphytic extracts. The metabolite pyrogallol appeared in the floral epiphytic community only after the treatment. The concentrations of the amino acid precursors of the ketoglutarate-synthesis pathway tended to decrease in the leaves and to increase in the foliar epiphytic extracts.ConclusionsThese results suggest that anaerobic and/or facultative anaerobic bacteria were present in high numbers in the phyllosphere and in the apoplasts of S. nigra. The results also show that microbial communities play a significant role in the metabolomes of plant organs and could have more complex and frequent mutualistic, saprophytic, and/or parasitic relationships with internal plant metabolism than currently assumed.

BackgroundThe phyllospheric microbiota is assumed to play a key role in the metabolism of host plants. Its role in determining the epiphytic and internal plant metabolome, however, remains to be investigated. We analyzed the Liquid Chromatography-Mass Spectrometry (LC-MS) profiles of the epiphytic and internal metabolomes of the leaves and flowers of Sambucus nigra with and without external antibiotic treatment application.ResultsThe epiphytic metabolism showed a degree of complexity similar to that of the plant organs. The suppression of microbial communities by topical applications of antibiotics had a greater impact on the epiphytic metabolome than on the internal metabolomes of the plant organs, although even the latter changed significantly both in leaves and flowers. The application of antibiotics decreased the concentration of lactate in both epiphytic and organ metabolomes, and the concentrations of citraconic acid, acetyl-CoA, isoleucine, and several secondary compounds such as terpenes and phenols in the epiphytic extracts. The metabolite pyrogallol appeared in the floral epiphytic community only after the treatment. The concentrations of the amino acid precursors of the ketoglutarate-synthesis pathway tended to decrease in the leaves and to increase in the foliar epiphytic extracts.ConclusionsThese results suggest that anaerobic and/or facultative anaerobic bacteria were present in high numbers in the phyllosphere and in the apoplasts of S. nigra. The results also show that microbial communities play a significant role in the metabolomes of plant organs and could have more complex and frequent mutualistic, saprophytic, and/or parasitic relationships with internal plant metabolism than currently assumed.

The synthesis of two novel BDPA-like radicals, a benzyl amino (BAm-BDPA, 7) and a cyano (CN-BDPA, 5) derivative, is reported and their behaviour as polarizing agents for fast dissolution Dynamic Nuclear Polarization (DNP) is evaluated. The radical 7 is a promising candidate for DNP studies since it is soluble in neat [1-13C]pyruvic acid (PA), and therefore the use of an additional glassing agent for sample homogeneity is avoided. In addition, a 60 mM sample of 7 offers optimum 13C NMR signal enhancements using fairly short polarization times (about 1800 s). It is shown that DNP-NMR measurements using 7 can be performed much more efficiently in terms of the signal enhancement per polarization build-up time unit than when using the reference OX63 or BDPA radicals. These enhanced features are translated to a substantial reduction of polarization times that represents an optimum temporary use of the DNP polarizer and allow economized liquid helium consumption.

Polyanionic and electroactive hybrids based on octasilsesquioxanes bearing metallacarborane units are developed. They show remarkable solubility in organic solvents and outstanding thermal stability. The metallacarboranes act as independent units simultaneously undergoing the reversible redox process.

© The Royal Society of Chemistry 2015. The synthesis, structural characterization and the successful application of a carbon centered radical derived from 1,3-bisdiphenylene-2-phenylallyl (BDPA), its benzyl alcohol derivative (BA-BDPA), as a polarizing agent for Dynamic Nuclear Polarization (DNP) are described. The reported BA-BDPA radical meets all the requirements to become a promising candidate for its use in in vivo DNP-NMR experiments: it is soluble in neat [1-13C]pyruvic acid, insoluble in the dissolution transfer solvent and is effective as a polarizing agent in fast dissolution DNP-NMR applications, without the need for using glassing agents. Moreover, it enables a simple but effective in-line radical filtration to obtain hyperpolarized solutions of [1-13C]pyruvic acid free of radicals that offers a better polarization performance. This journal is

Intramolecular stereoselective carboligations are important reactions in organic synthetic chemistry essential for the access of natural occurring compounds and analogues. Besides the chemical methodologies, a plethora of intramolecular C-C bond forming reactions exists in different metabolic pathways of living organism catalyzed by highly evolved enzymes. Examples of carboligases such as of aldolases or ThDP depending enzymes performing asymmetric intramolecular aldol reactions with synthetic substrates are scarce in the literature. In this work, we endeavored to investigate on the intramolecular C-C bond formation via benzoin reaction catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I (BAL). We investigate BAL-catalyzed intramolecular benzoin reaction on benzaldehyde moieties substrates connected with a spacer derivative via ether linkage (i.e. 2,2'- (1), 3,3’ (2) and 4,4’ (3)-(n-alkane-1,n-diylbis(oxy))dibenzaldehyde derivatives). The reaction performance comparing the intra and inter benzoin reaction with substrates 1-3 as well as their analogues with symmetric and unsymmetrical aromatic substitutions was investigated. The results obtained of substrate conversion, stereochemical outcome of the enzymatic reactions and molecular models that intended to explain the reactivity of the different substrates will be reported.

The synthesis and characterization of a set of poly(aryl ether) dendrimers with tetraphenylporphyrin as the core and 4, 8, 16, or 32 closo-carborane clusters are described. A regioselective hydrosilylation reaction on the allyl-terminated functions with carboranylsilanes in the presence of Karstedt's catalyst leads to different generations of boron-enriched dendrimers. This versatile approach allows the incorporation of a large number of boron atoms in the dendrimers' periphery. Translational diffusion coefficients (D) determined by DOSY NMR experiments permit estimation of the hydrodynamic radius (RH) and molecular size for each dendrimer. Furthermore, a notable correlation between D and the molecular weight (MW) is found and can be used to predict their overall size and folding properties. The UV-vis and emission behavior are not largely affected by the functionalization, therefore implying that the presence of carboranes does not alter their photoluminescence properties.

Palladium nanoparticles stabilized with tris-imidazolium tetrafluoroborates catalyze the stereoselective hydrosilylation of internal alkynes in a dry inert atmosphere to give (E)-vinylsilanes in excellent yields. In the presence of controlled amounts of water a transfer hydrogenation reaction takes place with the formation of (Z)-alkenes or the corresponding alkanes.

Palladium nanoparticles stabilized with tris-imidazolium tetrafluoroborates catalyze the stereoselective hydrosilylation of internal alkynes in a dry inert atmosphere to give (E)-vinylsilanes in excellent yields. In the presence of controlled amounts of water a transfer hydrogenation reaction takes place with the formation of (Z)-alkenes or the corresponding alkanes.

La plata és avui dia àmpliament utilitzada en catàlisi homogènia per a la síntesi de compostos orgànics a causa del seu caràcter d’àcid de Lewis i el seu poder oxidant. La Ag(I) és un potent oxidant monoelectrònic que troba utilitat en un gran nombre de processos catalítics. Tanmateix, els cicles catalítics de dos electrons, molt comuns en la química organometàl·lica dels metalls nobles, no han estat mai considerats possibles per a la plata. En aquest estudi descrivim un cicle catalític Ag(I)/Ag(III) que és operatiu en una reacció model d’acoblament creuat per a la formació d’enllaços C–O. Espècies aril–Ag(III) han estat inequívocament identificades com a intermedis d’aquest cicle catalític. L’estudi de la síntesi i la reactivitat de l’esmentat complex ha permès per primera vegada la caracterització de les etapes d’addició oxidant i eliminació reductiva de formació d’enllaços carboni–nucleò-fil en centres monometàl·lics de plata. El present treball demostra que els processos d’eliminació reductiva en espècies aril–Ag(III) són efectius en reaccions d’acoblament creuat per a la formació d’enllaços C–O, C–N, C–S, C–C i C–halur, incloses les reaccions de fluoració d’arils. Aquest estudi suposa un punt de partida per a l’expansió de la química redox Ag(I)/Ag(III) a noves metodologies per a la síntesi orgànica, en analogia a la química d’acoblament creuat del coure o el pal·ladi. A més, els resultats descrits proporcionen una comprensió mecanística fonamental única en les reaccions d’acoblament, Silver is extensively used in homogeneous catalysis for organic synthesis owing to its Lewis acidity and unique high oxidation power. The high oxidation potential of Ag(I) makes it a powerful one-electron oxidant that finds utility in a large number catalytic processes. However, two-electron redox catalytic cycles, most common in noble metal organometallic reactivity, have never been considered. Herein we show that an Ag(I)/Ag(III) catalytic cycle is operative in a model C–O cross-coupling reaction. Aryl–Ag(III) species have been unequivocally identified as an intermediate in the catalytic cycle. The study of the synthesis and reactivity of this complex has enabled for the first time the direct characterization of aryl halide oxidative addition and carbon–nucleophile bond-forming reductive elimination steps at monometallic silver centers. This report demonstrates that reductive elimination processes at aryl–Ag(III) species are effective for C–O, C–N, C–S, C–C and C–halide coupling reactions, including aryl fluorination. We anticipate our study as the starting point for expanding Ag(I)/Ag(III) redox chemistry into new methodologies for organic synthesis, resembling well-known copper or palladium cross-coupling catalysis. Furthermore, findings described herein provide a unique fundamental mechanistic understanding of Ag-catalyzed cross-coupling reactions and dismiss the generally accepted conception that silver redox chemistry can only arise from one-electron processes.Keywords: Cross-coupling, high oxidation states, redox chemistry, reaction mechanisms, silver.

Since fullerenes are available in macroscopic quantities from fullerene soot, large efforts have been geared toward designing efficient strategies to obtain highly pure fullerenes, which can be subsequently applied in multiple research fields. Here we present a supramolecular nanocage synthesized by metal-directed self-assembly, which encapsulates fullerenes of different sizes. Direct experimental evidence is provided for the 1:1 encapsulation of C60, C70, C76, C78 and C84, and solid state structures for the host–guest adducts with C60 and C70 have been obtained using X-ray synchrotron radiation. Furthermore, we design a washingbased strategy to exclusively extract pure C60 from a solid sample of cage charged with a mixture of fullerenes. These results showcase an attractive methodology to selectively extract C60 from fullerene mixtures, providing a platform to design tuned cages for selective extraction of higher fullerenes. The solid-phase fullerene encapsulation and liberation represent a twist in host–guest chemistry for molecular nanocage structures.

A straightforward chemo-enzymatic synthesis of new polyhydroxylated benzopyrrolizidines and cyclohexapyrrolizidines is developed. The two-step strategy consists of l-fuculose-1-phosphate aldolase variant F131A-catalyzed aldol addition of dihydroxyacetone phosphate to rac-N-benzyloxycarbonylindoline- 2-carbaldehyde as well as (2S*,3aS*,7aS*)- and (2S*,3aR*,7aR*)-N-benzyloxycarbonyloctahydroindole-2- carbaldehydes and a subsequent one-step catalytic deprotection-reductive amination. © 2014 American Chemical Society.

La plata és avui dia àmpliament utilitzada en catàlisi homogènia per a la síntesi de compostos orgànics a causa del seu caràcter d’àcid de Lewis i el seu poder oxidant. La Ag(I) és un potent oxidant monoelectrònic que troba utilitat en un gran nombre de processos catalítics. Tanmateix, els cicles catalítics de dos electrons, molt comuns en la química organometàl·lica dels metalls nobles, no han estat mai considerats possibles per a la plata. En aquest estudi descrivim un cicle catalític Ag(I)/Ag(III) que és operatiu en una reacció model d’acoblament creuat per a la formació d’enllaços C–O. Espècies aril–Ag(III) han estat inequívocament identificades com a intermedis d’aquest cicle catalític. L’estudi de la síntesi i la reactivitat de l’esmentat complex ha permès per primera vegada la caracterització de les etapes d’addició oxidant i eliminació reductiva de formació d’enllaços carboni–nucleò-fil en centres monometàl·lics de plata. El present treball demostra que els processos d’eliminació reductiva en espècies aril–Ag(III) són efectius en reaccions d’acoblament creuat per a la formació d’enllaços C–O, C–N, C–S, C–C i C–halur, incloses les reaccions de fluoració d’arils. Aquest estudi suposa un punt de partida per a l’expansió de la química redox Ag(I)/Ag(III) a noves metodologies per a la síntesi orgànica, en analogia a la química d’acoblament creuat del coure o el pal·ladi. A més, els resultats descrits proporcionen una comprensió mecanística fonamental única en les reaccions d’acoblament, Silver is extensively used in homogeneous catalysis for organic synthesis owing to its Lewis acidity and unique high oxidation power. The high oxidation potential of Ag(I) makes it a powerful one-electron oxidant that finds utility in a large number catalytic processes. However, two-electron redox catalytic cycles, most common in noble metal organometallic reactivity, have never been considered. Herein we show that an Ag(I)/Ag(III) catalytic cycle is operative in a model C–O cross-coupling reaction. Aryl–Ag(III) species have been unequivocally identified as an intermediate in the catalytic cycle. The study of the synthesis and reactivity of this complex has enabled for the first time the direct characterization of aryl halide oxidative addition and carbon–nucleophile bond-forming reductive elimination steps at monometallic silver centers. This report demonstrates that reductive elimination processes at aryl–Ag(III) species are effective for C–O, C–N, C–S, C–C and C–halide coupling reactions, including aryl fluorination. We anticipate our study as the starting point for expanding Ag(I)/Ag(III) redox chemistry into new methodologies for organic synthesis, resembling well-known copper or palladium cross-coupling catalysis. Furthermore, findings described herein provide a unique fundamental mechanistic understanding of Ag-catalyzed cross-coupling reactions and dismiss the generally accepted conception that silver redox chemistry can only arise from one-electron processes.Keywords: Cross-coupling, high oxidation states, redox chemistry, reaction mechanisms, silver.

A facile one-step polymerization strategy is explored to achieve novel catechol-based materials. Depending on the functionality of the catechol, the as-prepared product can be used to modify at will the surface tension of nano and bulk structures, from oleo-/hydrophobic to highly hydrophilic. A hydrophobic catechol prepared thus polymerized shows the ability to self-assemble as solid nanoparticles with sticky properties in polar solvent media. Such a versatile concept is ideal for the development of catechol-based multifunctional materials. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aldol addition reactions of dihydroxyacetone (DHA) to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate aldolase (RhuA) in the presence of borate buffer are reported. High yields of aldol adduct (e.g. 70–90%) were achieved with excellent (>98 : 2 syn/anti) stereoselectivity for most S or R configured acceptors, which compares favorably to the reactions performed with DHAP. The stereochemical outcome was different and depended on the N-Cbz-amino aldehyde enantiomer: the S acceptors gave the syn (3R,4S) aldol adduct whereas the R ones gave the anti (3R,4R) diastereomer. Moreover, the tactical use of Cbz protecting group allows simple and efficient elimination of borate and excess of DHA by reverse phase column chromatography or even by simple extraction. This, in addition to the use of unphosphorylated donor nucleophile, makes a useful and expedient methodology for the synthesis of structurally diverse iminocyclitols. The performance of aldol additions of dihydroxyacetone phosphate (DHAP) to N-Cbz-amino aldehydes using RhuA and L-fuculose-1-phosphate aldolase (FucA) catalyst in borate buffer was also evaluated. For FucA catalysts, including FucA F131A, the initial velocity of the aldol addition reactions using DHAP were between 2 and 10 times faster and the yields between 1.5 and 4 times higher than those in triethanolamine buffer. In this case, the retroaldol velocities measured for some aldol adducts were lower than those without borate buffer indicating some trapping effect that could explain the improvement of yields.

Structure-guided re-design of the acceptor binding site of D-fructose-6-phosphate aldolase from E. coli leads to the construction of FSA A129S/A165G double mutant with an activity between 5- to >900-fold higher than that of wild-type towards N-Cbz-aminoaldehyde derivatives.

The aldol addition of unphosphorylated dihydroxyacetone (DHA) to aldehydes catalyzed by L-rhamnulose-1-phosphate aldolase (RhuA), a dihydroxyacetone phosphate-dependent aldolase, is reported. Moreover, a single point mutation in the phosphate binding site of the RhuA wild type, that is, substitution of aspartate for asparagine at position N29, increased by 3-fold the equation image of aldol addition reactions of DHA to other aldehyde acceptors rather than the natural L-lactaldehyde. The RhuA N29D mutant modified the optimum enzyme design for the natural substrate and changed its catalytic properties making the aldolase more versatile to other aldol additions of DHA.

A new set of Ru−Cl complexes containing either the pinene[5,6]bpea ligand (L1) or the C₃ symmetric pinene[4,5]tpmOMe (L2) tridentate ligand in combination with the bidentate (B) 2,2′-bipyridine (bpy) or 1,2-diphenylphosphinoethane (dppe) with general formula [RuCl(L1 or L2)(B)]⁺ have been prepared and thoroughly characterized. In the solid state, X-ray diffraction analysis techniques have been used. In solution, cyclic voltammetry (CV) and 1D and 2D NMR spectroscopy have been employed. DFT calculations have been also performed on these complexes and their achiral analogues previously reported in our group, to interpret and complement experimental results. Whereas isomerically pure complexes ([RuIICl(L2)(bpy)](BF₄), 5 and [RuIICl(L2)(dppe)](BF₄), 6) are obtained when starting from the highly symmetric [RuIIICl₃(L2)], 2, isomeric mixtures of cis,fac-[RuIICl(L1)(bpy)](BF₄) (3b/3b′), trans,fac- (3a) and up/down,mer- (3c, 3d) isomers are formed when bpy is added to the less symmetric [RuIIICl₃(L1)], 1, in contrast to the case of the bulky dppe ligand that, upon coordination to 1, leads to the trans,fac-[RuIICl(L1)(dppe)](BF₄) (4a) complex as a sole isomer due to steric factors.

A novel straightforward chemoenzymatic procedure for the synthesis of hyacinthacine stereoisomers based on the aldol addition of dihydroxyacetone phosphate (DHAP) to N-Cbz-prolinal under catalysis by l-rhamnulose 1-phosphate aldolase from E. coli is presented. The synthesis is complemented by a simple and effective purification protocol consisting of ion-exchange chromatography on CM-sepharose. As examples, ( )-hyacinthacine A2 [the enantiomer of (+)-hyacinthacine A2], 7-deoxy- 2-epialexine (the enantiomer of 3-epihyacinthacine A2), ent-7-deoxyalexine (the enantiomer of 7-deoxyalexine) and 2-epihyacinthacine A2 were synthesized by these procedures and characterized for the first time. These new isomers were assayed as inhibitors of glycosidases. As a result, ( )-hyacinthacine A2 demonstrated to be a good inhibitor of a-d-glucosidase from rice whereas the natural enantiomer, hyacinthacine A2, was not. Moreover, a new family of inhibitors of a-l-rhamnosidase was uncovered.

This work examines the influence of N-protecting groups on the conversion and stereoselectivity of dihydroxyacetone phosphate (DHAP) dependent aldolase-catalyzed aldol additions of DHAP to N-protected-3-aminopropanal. Phenylacetyl-(PhAc-), tert-butyloxycarbonyl- (tBoc-) and fluoren-9-ylmethoxycarbonyl- (Fmoc-)-3-aminopropanal were evaluated as substrates for d-fructose 1,6-bisphosphate aldolase from rabbit muscle (RAMA), and l-rhamnulose-1-phosphate aldolase (RhuA) and l-fuculose-1-phosphate aldolase (FucA), both from Escherichia coli. Using PhAc and tBoc ca. 70% conversions to the aldol adduct were achieved, whereas Fmoc gave maximum conversions of ca. 25%. The stereoselectivity of the DHAP-aldolases did not depend on the N-protected-3-aminopropanal derivative. Moreover, inversion of FucA stereoselectivity relative to that obtained with the natural l-lactaldehyde was observed. Both N-PhAc and tBoc adduct product derivatives were successfully deprotected by penicillin G acylase (PGA)-catalyzed hydrolysis at pH 7 and by treatment with aqueous TFA (6% v/v), respectively. However, the corresponding cyclic imine sugars could not be isolated, presumable due to the presence of a highly reactive primary amine and a keto group in the molecule, which lead to a number of unexpected reactions.

The potential of L-fuculose-1-phosphate aldolase (FucA) as a catalyst for the asymmetric aldol addition of dihydroxyacetone phosphate (DHAP) to N-protected amino aldehydes has been investigated. First, the reaction was studied in both emulsion systems and conventional dimethylformamide (DMF)/H2O (1:4 v/v) mixtures. At 100 mM DHAP, compared with the reactions in the DMF/H2O (1:4) mixture, the use of emulsion systems led to two- to three-fold improvements in the conversions of the FucA-catalyzed reactions. The N-protected aminopolyols thus obtained were converted to iminocyclitols by reductive amination with Pd/C. This reaction was highly diastereoselective with the exception of the reaction of the aldol adduct formed from (S)-N-Cbz-alaninal, which gave a 55:45 mixture of both epimers. From the stereochemical analysis of the resulting iminocyclitols, it was concluded that the stereoselectivity of the FucA-catalyzed reaction depended upon the structure of the N-Cbz-amino aldehyde acceptor. Whereas the enzymatic aldol reaction with both enantiomers of N-Cbz-alaninal exclusively gave the expected 3R,4R configuration, the stereochemistry at the C-4 position of the major aldol adducts produced in the reactions with N-Cbz-glycinal and N-Cbz-3-aminopropanal was inverted to the 3R,4S configuration. The study of the FucA-catalyzed addition of DHAP to phenylacetaldehyde and benzyloxyacetaldehyde revealed that the 4R product was kinetically favored, but rapidly disappeared in favor of the 4S diastereoisomer. Computational models were generated for the situations before and after CC bond formation in the active site of FucA. Moreover, the lowest-energy conformations of each pair of the resulting epimeric adducts were determined. The data show that the products with a 3R,4S configuration were thermodynamically more stable and, therefore, the major products formed, in agreement with the experimental results.

The potential of dihydroxyacetone phosphate (DHAP)-dependent aldolases to catalyze stereoselective aldol additions is, in many instances, limited by the solubility of the acceptor aldehyde in aqueous/co-solvent mixtures. Herein, we demonstrate the efficiency of emulsion systems as reaction media for the class I fructose-1,6-bisphosphate aldolase (RAMA) and class II recombinant rhamnulose-1-phosphate aldolase from E. coli (RhuA)-catalyzed aldol addition between DHAP and N-benzyloxycarbonyl (N-Cbz) aminoaldehydes. The use of emulsions improved the RAMA-catalyzed aldol conversions by three to tenfold relative to those in conventional DMF/water mixtures. RhuA was more reactive than RAMA towards the N-Cbz aminoaldehydes regardless of the reaction medium. With (S)- or (R)-Cbz-alaninal, RAMA exhibited preference for the R enantiomer, while RhuA had no enantiomeric discrimination. The linear N-Cbz aminopolyols thus obtained were submitted to catalytic intramolecular reductive amination to afford the corresponding iminocyclitols. This reaction was diastereoselective in all cases examined; the face selectivity was controlled by the stereochemistry of the newly formed hydroxyl group originating from the aldehyde. Characterization of the resulting iminocyclitols allowed the assessment of the diastereoselectivity of the enzymatic aldol reactions with respect to the N-protected aminoaldehyde. RAMA formed single diastereoisomers from N-Cbz-glycinal and from both enantiomers of N-Cbz-alaninal, while 14 % of the epimeric product was observed from N-Cbz-3-aminopropanal. Diastereoselectivity from RhuA was lower than that observed from RAMA. Interestingly, a single diastereoisomer was formed from (S)-Cbz-alaninal, whereas only a 34 % diastereomeric excess was observed from its enantiomer (i.e., (R)-Cbz-alaninal).

New polypyridylic chiral ligands, having either C₃ or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-α-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has been achieved through a new aldehyde building block ((-)-16). As an example, the synthesis of a chiral derivative of N,N-bis(2-pyridylmethyl)ethylamine (bpea) ligand, (-)-19, has been performed to illustrate the viability of the method. The coordinative ability of the ligands has been tested through the synthesis and characterization of complexes [Mn((-)-19)Br₂], (-)-20, and [RuCl((-)-10)(bpy)](BF₄), (-)-21. Some preliminary results related to the enantioselective catalytic epoxidation of styrene with the ruthenium complex are also presented.

A new set of Ru−Cl complexes containing either the pinene[5,6]bpea ligand (L1) or the C₃ symmetric pinene[4,5]tpmOMe (L2) tridentate ligand in combination with the bidentate (B) 2,2′-bipyridine (bpy) or 1,2-diphenylphosphinoethane (dppe) with general formula [RuCl(L1 or L2)(B)]⁺ have been prepared and thoroughly characterized. In the solid state, X-ray diffraction analysis techniques have been used. In solution, cyclic voltammetry (CV) and 1D and 2D NMR spectroscopy have been employed. DFT calculations have been also performed on these complexes and their achiral analogues previously reported in our group, to interpret and complement experimental results. Whereas isomerically pure complexes ([RuIICl(L2)(bpy)](BF₄), 5 and [RuIICl(L2)(dppe)](BF₄), 6) are obtained when starting from the highly symmetric [RuIIICl₃(L2)], 2, isomeric mixtures of cis,fac-[RuIICl(L1)(bpy)](BF₄) (3b/3b′), trans,fac- (3a) and up/down,mer- (3c, 3d) isomers are formed when bpy is added to the less symmetric [RuIIICl₃(L1)], 1, in contrast to the case of the bulky dppe ligand that, upon coordination to 1, leads to the trans,fac-[RuIICl(L1)(dppe)](BF₄) (4a) complex as a sole isomer due to steric factors.