RESUMEN
Alkyl glycosides and sugars esters are non-ionic surfactants of interest for various applications (cosmetics, food, detergency, ). In the present study, xylans and cellulose from wheat bran were enzymatically converted into pentyl xylosides and glucose and xylose laurate monoesters. Transglycosylation reaction catalyzed by the commercial enzymatic cocktail Cellic Ctec2 in the presence of pentanol led to the synthesis of pentyl ß-D-xylosides from DP1 to 3 with an overall yield of 520 mg/g of xylans present in wheat bran. Enzymatic hydrolysis of wheat bran with Cellic Ctec2 and subsequent acylation of the recovered D-glucose and D-xylose catalyzed by the commercial lipase N435 in the presence of lauric acid or methyl laurate produced one D-glucose laurate monoester and one D-xylose laurate monoester. An integrated approach combining transglycosylation and (trans)esterification reactions was successfully developed to produce both pentyl xylosides and D-glucose and D-xylose laurate esters from the same batch of wheat bran.
RESUMEN
The deprotonation of differently substituted propargyl xylosides with s-BuLi/TMEDA followed by protonation with t-butanol at -115 °C provided a range of new axially chiral 1,3-disubstituted alkoxyallenes in a diastereoselective way. Numerous reaction parameters such as solvent, temperature, or protonating agent were examined as well as protecting groups on the xyloside moiety and the influence of the substituents on the alkyne part. The configuration of the main diastereoisomer of 3-methyl-1-xyloside-allene was determined for the first time by single-crystal X-ray diffraction analysis and nOe NMR experiments. Furthermore, DFT calculations on the propargyl/allenyl lithium intermediates formed in the course of the deprotonation reaction provided new structural insights of these complexes. The subsequent protonation process with alcohols was investigated by theoretical surface exploration, revealing the importance of the approach of the alcohol toward the lithium compounds on the reaction outcome.
RESUMEN
Synthetic analogues of the naturally occurring iminosugar homoDMDP, which feature a perfluoroalkyl group at the pseudo-anomeric position, have been synthesized from the corresponding sugar-derived cyclic aldonitrone. The new fluorinated iminosugars as well as homoDMDP and its 6-deoxy counterpart were evaluated for their inhibitory activity against a panel of glycosidases. While the replacement of the (1',2')-dihydroxyethyl substituent of homoDMDP with -C4F9 proved detrimental for enzyme binding, introduction of a -C3F7 moiety tuned the inhibitory activity spectrum selectively towards α-fucosidase and α-glucosidase from yeast.
Asunto(s)
Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Glicósido Hidrolasas/antagonistas & inhibidores , Iminoazúcares/síntesis química , Iminoazúcares/farmacología , Alquilación , Aspergillus/enzimología , Técnicas de Química Sintética , Inhibidores Enzimáticos/química , Iminoazúcares/química , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Efficient enzymatic synthesis of d-xylose and l-arabinose lauryl mono- and diesters has been achieved by transesterification reactions catalysed by immobilized Candida antarctica lipase B as biocatalyst, in organic medium in the presence of d-xylose or l-arabinose and vinyllaurate at 50⯰C. In case of l-arabinose, one monoester and one diester were obtained in a 57% overall yield. A more complex mixture was produced for d-xylose as two monoesters and two diesters were synthesized in a 74.9% global yield. The structures of all these pentose laurate esters was solved. Results demonstrated that the esterification first occurred regioselectively onto the primary hydroxyl groups. Pentose laurate esters exhibited interesting features such as low critical aggregation concentrations values all inferior to 25⯵M. Our study demonstrates that the enzymatic production of l-arabinose and d-xylose-based esters represents an interesting approach for the production of green surfactants from lignocellulosic biomass-derived pentoses.
Asunto(s)
Arabinosa/análogos & derivados , Tensoactivos/metabolismo , Xilosa/análogos & derivados , Arabinosa/biosíntesis , Arabinosa/química , Biocatálisis , Biomasa , Estabilidad de Medicamentos , Enzimas Inmovilizadas/metabolismo , Esterificación , Ésteres/química , Ésteres/metabolismo , Proteínas Fúngicas/metabolismo , Tecnología Química Verde , Humanos , Concentración de Iones de Hidrógeno , Lauratos/química , Lauratos/metabolismo , Lipasa/metabolismo , Estructura Molecular , Tensoactivos/química , Tensoactivos/farmacología , Xilosa/biosíntesis , Xilosa/químicaRESUMEN
Different mono-xylosides and their corresponding xylobiosides obtained by a chemo-enzymatic approach featuring various substituents attached to a triazole ring were probed as priming agents for glycosaminoglycan (GAG) biosynthesis in the xylosyltransferase-deficient pgsA-745 Chinese hamster ovary cell line. Xylosides containing a hydrophobic aglycone moiety were the most efficient priming agents. Mono-xylosides induced higher GAG biosynthesis in comparison with their corresponding xylobiosides. The influence of the degree of polymerization of the carbohydrate part on the priming activity was investigated through different experiments. We demonstrated that in case of mono-xylosides, the cellular uptake as well as the affinity and the catalytic efficiency of ß-1,4-galactosyltransferase 7 were higher than for xylobiosides. Altogether, these results indicate that hydrophobicity of the aglycone and degree of polymerization of glycone moiety were critical factors for an optimal priming activity for GAG biosynthesis.
Asunto(s)
Glicosaminoglicanos/biosíntesis , Glicósidos/química , Glicósidos/metabolismo , Animales , Células CHO , Cricetulus , Galactosiltransferasas/genética , Galactosiltransferasas/metabolismo , Humanos , Pentosiltransferasa/genética , Pentosiltransferasa/metabolismo , Relación Estructura-Actividad , UDP Xilosa Proteína XilosiltransferasaRESUMEN
A series of diastereomeric tetrahydroxylated azepanes featuring a carboxymethyl group at the pseudo-anomeric position have been synthesized from a common unsaturated intermediate. Syn- and anti-dihydroxylation reactions were achieved to yield the target compounds after efficient one-step deprotection of carbamate, ester and acetonide groups simultaneously. Screening of these polyhydroxylated azepanes toward a range of commercially available glycosidases was performed and one of the stereoisomers showed potent and selective inhibition toward ß-galactosidase (IC50=21 µM).
Asunto(s)
Azepinas/síntesis química , Azepinas/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Glicósido Hidrolasas/antagonistas & inhibidores , Azepinas/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Modelos Moleculares , Espectroscopía de Protones por Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , EstereoisomerismoRESUMEN
An unprecedented reactivity of CF3-TMS has been revealed, which exploits the basic character of the generated [CF3(-)] capable of delivering dichloromethide from dichloromethane with subsequent transfer to nitrones under smooth conditions. The proton-abstraction pathway was demonstrated through isotopic labeling experiments in CD2Cl2. The same reaction was achieved in acetonitrile with the introduction of a cyanomethyl group onto the nitrones.
RESUMEN
The synthesis of new class of potential TPase inhibitors containing a difluoromethylphosphonate function as phosphate mimic is reported. This new series was prepared from a readily available fluorinated building block in few steps. Two series were evaluated as potential inhibitors: a linear series and a conformational constrained series. The activity of these multisubstrate inhibitors depends on the size of the spacer introduced between the pyrimidine ring and the phosphonate function. Best results were observed from triazolyl derivatives, easily obtained from propargylthymine and corresponding azides.
Asunto(s)
Inhibidores de la Angiogénesis/síntesis química , Nucleósidos/síntesis química , Organofosfonatos/síntesis química , Timidina Fosforilasa/antagonistas & inhibidores , Inhibidores de la Angiogénesis/química , Cristalografía por Rayos X , Escherichia coli/enzimología , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Nucleósidos/química , Organofosfonatos/química , Relación Estructura-Actividad , Especificidad por Sustrato , Timidina Fosforilasa/químicaRESUMEN
This paper describes a convenient and efficient synthesis of new complexing surfactants from d-galacturonic acid and n-octanol as renewable raw materials in a two-step sequence. In the first step, simultaneous O-glycosidation-esterification under Fischer conditions was achieved. The anomeric ratio of the products was studied based on the main experimental parameters and the activation mode (thermal or microwave). In the second step, aminolysis of the n-octyl ester was achieved with various functionalized primary amines under standard thermal or microwave activation. The physico-chemical properties of these new amphiphilic ligands were measured and these compounds were found to exhibit interesting surface properties. Complexing abilities of one uronamide ligand functionalized with a pyridine moiety toward Cu(II) ions was investigated in solution by EPR titrations. A solid compound was also synthesized and characterized, its relative structure was deduced from spectroscopic data.
Asunto(s)
Ácidos Hexurónicos/química , Ligandos , Espectroscopía de Resonancia por Spin del Electrón , Microondas , Modelos Químicos , Estructura MolecularRESUMEN
This review is dedicated to wheat hemicelluloses and its main components D-xylose and L-arabinose as raw materials for fine organic chemistry. The context of the wheat agro-industry, its by-products, and extraction and hydrolysis of hemicelluloses to produce the pentoses are considered. The straightforward preparation of pentose-based surfactants, their properties, and their situation in the field of carbohydrate-based surfactants are addressed. Multistep transformations of pentoses are also described, first from a methodology point of view, with the aim of producing multifunctional enantiopure building-blocks, then considering targeted natural and/or bioactive products. Selected reactions of furfural, an important dehydration product of pentoses, are also presented.
RESUMEN
Nitrogen-in-the-ring analogues of l-fucose and l-rhamnose were prepared, which feature a spirocyclopropyl moiety in place of the methyl group of the natural sugar. The synthetic route involved a titanium-mediated aminocyclopropanation of a glycononitrile as the key step. Four new spirocyclopropyl iminosugar analogues were generated, which displayed some activity towards l-fucosidase and l-rhamnosidase.
Asunto(s)
Ciclopropanos/síntesis química , Inhibidores Enzimáticos/síntesis química , Fucosa/análogos & derivados , Ramnosa/análogos & derivados , Compuestos de Espiro/síntesis química , Ciclopropanos/química , Ciclopropanos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Fucosa/síntesis química , Fucosa/química , Fucosa/farmacología , Glicósido Hidrolasas/antagonistas & inhibidores , Glicósido Hidrolasas/metabolismo , Cinética , Espectroscopía de Resonancia Magnética , Rotación Óptica , Ramnosa/síntesis química , Ramnosa/química , Ramnosa/farmacología , Espectrometría de Masa por Ionización de Electrospray , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , alfa-L-Fucosidasa/antagonistas & inhibidores , alfa-L-Fucosidasa/metabolismoRESUMEN
The biological activity of unsaturated iminosugars has not yet been extensively studied because of a lack of general synthetic methods. A practical synthesis of these cyclic ketimine sugars was developed, which was based on a tandem addition-cyclization reaction of a Grignard reagent to a omega-methanesulfonylglycononitrile.
Asunto(s)
Iminoazúcares/síntesis química , Pirroles/síntesis química , Benceno/química , Ciclización , Ésteres/química , Iminoazúcares/química , Estructura Molecular , Pirroles/químicaRESUMEN
The transformation of D-xylose and L-arabinose, the two major components of wheat straw and bran, into a unique multifunctional, optically pure, five-carbon synthon has been achieved. The synthetic sequence requires three steps: suitable protection of the hydroxyl groups of the pentoses, introduction of an iodide at the C-5 position and zinc-mediated opening of the furanose ring leading to the formation of a common substituted pent-4-enal.
Asunto(s)
Arabinosa/química , Polisacáridos/química , Triticum/química , Xilosa/química , Estructura MolecularRESUMEN
In the framework of a project devoted to the chemical transformation of monosaccharides from hemicelluloses into higher added value materials, the zinc-induced reductive elimination from 5-deoxy-5-iodo derivatives of D-xylose and L-arabinose was carried out. This study gave us the opportunity to observe surprising behaviors. In particular, the reaction strongly depends on structural parameters (protecting group pattern, configuration at C-4) and on the presence of Zn2+ ions. Collaterally with the experimental work, water solvent PCM HF-DFT (MPW1K/LANL2DZ) computations were performed to obtain insight into the mechanism for the reductive part of the reaction sequence. Without Zn2+, the zinc insertion reaction was found to proceed through a concerted but non-synchronous process involving a relatively large energy barrier (32 kcal mol-1) that directly leads to the presumed organozinc intermediate. In the presence of Zn2+, a three-step mechanism was identified in which the cation coordinates the anomeric and ring oxygen atoms and also the sugar iodine atom, causing an activating effect on the zinc insertion process by facilitating the homolytic rupture of the C-I bond. Complexes between zinc and Zn2+ bound carbohydrates were characterized with large stabilization energies, suggesting that Zn2+ might enhance the affinity of the organic compound with the zinc metal surface.
Asunto(s)
Arabinosa/química , Glucósidos/química , Indoles/química , Xilosa/química , Zinc/química , Cationes Bivalentes/química , Espectrometría de Masas , Modelos Moleculares , Conformación Molecular , Oxidación-ReducciónRESUMEN
A highly diastereoselective nucleophilic mono(trifluoromethylation) of a tartaric acid-based diketone, using trifluoromethyl(trimethyl)silane, afforded the corresponding gamma-keto trifluoromethylcarbinol. The scope and limitation of this reaction was studied. The acidic removal of the acetonide moiety protecting the two hydroxyl groups of the adducts was unsuccessful. Bis(O-methylation) of the aromatic derivatives under basic conditions, followed by acidic hydrolysis and oxidative cleavage, led to two different enantiopure products: an alpha-aryl-alpha-methoxy-alpha-trifluoromethyl ethanal and an alpha-aryl-alpha-methoxycarboxylic acid. The overall process is eventually an interesting way to convert one natural chiral raw material into two functionalized enantiopure building blocks including a trifluoromethyl one.
RESUMEN
Polyhydroxy 4-azaspiro[2.4]heptane derivatives (spirocyclopropyl iminosugars) were prepared in four to six steps from readily available protected aldoses. The key step of the reaction sequence involves a titanium-mediated aminocyclopropanation of glycononitriles with subsequent cyclization. Five new polyhydroxypyrrolidines so-obtained have been evaluated for their ability to inhibit 16 glycosidases. One of them exhibits selective inhibition of alpha-L-fucosidase from bovine kidney (Ki=1.6 microM, competitive).
Asunto(s)
Inhibidores Enzimáticos/farmacología , Pirrolidinas/farmacología , Compuestos de Espiro/química , alfa-L-Fucosidasa/antagonistas & inhibidores , Animales , Bovinos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Riñón/enzimología , Conformación Molecular , Pirrolidinas/síntesis química , Pirrolidinas/química , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
The interactions of three bis(amide) ligands derived from tartaric acid with copper (II) were investigated in aqueous solution by a combination of potentiometry, UV-vis spectrophotometry, electron paramagnetic resonance (EPR), and mass spectrometry. The formation constants of the complexes were measured and their relative structures were reported. The sites of complexation of these ligands are investigated based mostly on their electronic and EPR spectra and on the comparison with the behaviour of some analog compounds.
RESUMEN
DGalactofuranose is a widespread component of cell wall polysaccharides in bacteria, protozoa and fungi, but is totally absent in mammals. Importantly, galactofuranose is a key constituent of major cell envelope polysaccharides in pathogenic mycobacteria. In this respect, galactofuranose-based glycoconjugates are interesting target molecules for drug design. O-Glycosidases and notably beta-D-galactofuranosidases could be useful tools for the chemoenzymatic synthesis of galactofuranosides, but to date no studies of this type have been reported. Here we report the use of a GH 51 alpha-l-arabinofuranosidase for the synthesis of beta-D-galactofuranosides. We have demonstrated that this enzyme can catalyse both the autocondensation of p-nitrophenyl-beta-D-galactofuranoside and the transgalactofuranosylation of benzyl alpha-D-xylopyranoside, forming p-nitrophenyl beta-D-galactofuranosyl-(1-->2)-beta-D-galactofuranoside and benzyl beta-D-galactofuranosyl-(1-->2)-alpha-D-xylopyranoside, respectively. Both reactions were very regiospecific and the reaction involving benzyl alpha-D-xylopyranoside afforded very high yields (74.8%) of the major product. To our knowledge, this demonstration of chemoenzymatic synthesis of galactofuranosides constitutes the very first use of an O-glycosidase for the synthesis of galactofuranosides.
Asunto(s)
Glicósido Hidrolasas/química , Glicósido Hidrolasas/síntesis química , Bacillaceae/enzimología , Catálisis , Escherichia coli/genética , Glicósido Hidrolasas/genética , Glicosilación , Hidrólisis , Cinética , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Proteínas Recombinantes/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
To date, the enzymatically-catalysed synthesis of pentose-containing compounds has been limited to the production of oligo-beta-(1-->3) and oligo-beta-(1-->4)-linked xylopyranosides. To our knowledge, no such syntheses have involved arabinofuranose or, indeed, any other sugars in the furanose configuration. In this report, we describe the use of a thermostable alpha-L-arabinofuranosidase for the synthesis of p-nitrophenyl alpha-L-arabinofuranosyl-(1-->2)-alpha-L-arabinofuranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->2)-beta-D-xylopyranoside, p-nitrophenyl beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranoside and benzyl alpha-D-xylopyranosyl-(1-->2)-alpha-L-arabinofuranoside. Importantly, this latter compound is synthesised in a highly regiospecific reaction, which leads to the production of a single disaccharide.