The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
Lahssen El Blidi - One of the best experts on this subject based on the ideXlab platform.
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fructose 1 6 bisphosphate aldolase mediated synthesis of Aminocyclitols analogues of valiolamine and their evaluation as glycosidase inhibitors
Chemcatchem, 2009Co-Authors: Lahssen El Blidi, Zeinab Assaf, Flora Camps Bres, H Veschambre, Vincent TheryAbstract:A highly stereoselective method for the preparation of nitro- and Aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol reaction of dihydroxyacetone phosphate (DHAP) on hydroxynitrobutanals, is reported. The key part of the synthesis is based on a one-pot /two-enzyme process whereby three reactions take place; rabbit muscle aldolase (RAMA) catalyzed aldolization, phytase-catalyzed phosphate hydrolysis, and intramolecular spontaneous nitroaldolization. Two families of nitrocyclitols were obtained depending on the carbon configuration in the β position to the nitro group. Reduction of the latter afforded the Aminocyclitols. Evaluation of the inhibition properties of the amines towards five commercially available glycosidases has shown selectivity for β-glucosidase and β-galactosidase.
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Fructose‐1,6‐Bisphosphate Aldolase‐Mediated Synthesis of Aminocyclitols (Analogues of Valiolamine) and their Evaluation as Glycosidase Inhibitors
ChemCatChem, 2009Co-Authors: Lahssen El Blidi, Jean Bolte, Zeinab Assaf, Flora Camps Bres, H Veschambre, Vincent Thery, Marielle LemaireAbstract:A highly stereoselective method for the preparation of nitro- and Aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol reaction of dihydroxyacetone phosphate (DHAP) on hydroxynitrobutanals, is reported. The key part of the synthesis is based on a one-pot /two-enzyme process whereby three reactions take place; rabbit muscle aldolase (RAMA) catalyzed aldolization, phytase-catalyzed phosphate hydrolysis, and intramolecular spontaneous nitroaldolization. Two families of nitrocyclitols were obtained depending on the carbon configuration in the β position to the nitro group. Reduction of the latter afforded the Aminocyclitols. Evaluation of the inhibition properties of the amines towards five commercially available glycosidases has shown selectivity for β-glucosidase and β-galactosidase.
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Synthèse chimioenzymatique et évaluation d'inhibiteurs potentiels de glycosidases, analogues de la valiolamine
2006Co-Authors: Lahssen El BlidiAbstract:Les glycosidases sont des enzymes impliquées dans un grand nombre de processus biologiques. Leurs inhibiteurs présentent un potentiel thérapeutique en tant qu'agents antidiabétiques, agents antiviraux ou agents pour traiter des maladies génétiques. Au cours de ce travail, nous nous sommes attachés à développer une voie de synthèse chimioenzymatique permettant d'accéder à des analogues de la valiolamine, puissant inhibiteurs d'alpha-glucosidases. Les Aminocyclitols que nous avions pour objectif de préparer diffèrent de la valiolamine par la position du groupement amino et des stéréochimies des hydroxyles. Nous avons synthétisé ces Aminocyclitols selon une méthode originale, basée sur un procédé en un seul pot mettant en jeu deux enzymes et trois réactions : une aldolisation catalysée par la fructose-1,6- biphosphate aldolase, une déphosphorylation catalysée par une phytase et une nitroaldolisation intramoléculaire. Ainsi deux liaisons C-C sont formées de façon hautement stéréosélective en une seule étape. Nous avons synthétisé neuf nouveaux Aminocyclitols et deux nouveaux zwitterions et dérivé N-alkylé. Quelque Aminocyclitols se sont révélés des inhibiteurs sélectifs de la béta-glucosidase d'amandes douces et de la béta-galactosidase d'Aspergillus oryzae.
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Straightforward chemo-enzymatic synthesis of new Aminocyclitols, analogues of valiolamine and their evaluation as glycosidase inhibitors.
Tetrahedron: Asymmetry, 2006Co-Authors: Lahssen El Blidi, Mustapha Ahbala, Jean Bolte, Marielle LemaireAbstract:An efficient fructose-1,6-bisphosphate aldolase mediated synthesis of new Aminocyclitol analogues of valiolamine is described. The one-pot process where four stereocentres are created involves the formation of two carbon–carbon bonds. One is catalysed by the aldolase, coupling dihydroxyacetone phosphate to nitrobutyraldehydes. The other is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketones. Depending on the configuration of the hydroxyl which is α to the nitro group, two series of configuration are accessible. The lipase resolution of the nitroalcohol ketal, precursor of the nitroaldehyde, is presented. The inhibition properties of the Aminocyclitols obtained after the reduction of the nitro group are evaluated towards five commercial glycosidases
Vincent Thery - One of the best experts on this subject based on the ideXlab platform.
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fructose 1 6 bisphosphate aldolase mediated synthesis of Aminocyclitols analogues of valiolamine and their evaluation as glycosidase inhibitors
Chemcatchem, 2009Co-Authors: Lahssen El Blidi, Zeinab Assaf, Flora Camps Bres, H Veschambre, Vincent TheryAbstract:A highly stereoselective method for the preparation of nitro- and Aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol reaction of dihydroxyacetone phosphate (DHAP) on hydroxynitrobutanals, is reported. The key part of the synthesis is based on a one-pot /two-enzyme process whereby three reactions take place; rabbit muscle aldolase (RAMA) catalyzed aldolization, phytase-catalyzed phosphate hydrolysis, and intramolecular spontaneous nitroaldolization. Two families of nitrocyclitols were obtained depending on the carbon configuration in the β position to the nitro group. Reduction of the latter afforded the Aminocyclitols. Evaluation of the inhibition properties of the amines towards five commercially available glycosidases has shown selectivity for β-glucosidase and β-galactosidase.
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Fructose‐1,6‐Bisphosphate Aldolase‐Mediated Synthesis of Aminocyclitols (Analogues of Valiolamine) and their Evaluation as Glycosidase Inhibitors
ChemCatChem, 2009Co-Authors: Lahssen El Blidi, Jean Bolte, Zeinab Assaf, Flora Camps Bres, H Veschambre, Vincent Thery, Marielle LemaireAbstract:A highly stereoselective method for the preparation of nitro- and Aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol reaction of dihydroxyacetone phosphate (DHAP) on hydroxynitrobutanals, is reported. The key part of the synthesis is based on a one-pot /two-enzyme process whereby three reactions take place; rabbit muscle aldolase (RAMA) catalyzed aldolization, phytase-catalyzed phosphate hydrolysis, and intramolecular spontaneous nitroaldolization. Two families of nitrocyclitols were obtained depending on the carbon configuration in the β position to the nitro group. Reduction of the latter afforded the Aminocyclitols. Evaluation of the inhibition properties of the amines towards five commercially available glycosidases has shown selectivity for β-glucosidase and β-galactosidase.
Antonio Delgado - One of the best experts on this subject based on the ideXlab platform.
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new glucocerebrosidase inhibitors by exploration of chemical diversity of n substituted Aminocyclitols using click chemistry and in situ screening
Journal of Medicinal Chemistry, 2011Co-Authors: Lucía Díaz, Jordi Bujons, Amadeu Llebaria, Josefina Casas, Antonio DelgadoAbstract:A library of Aminocyclitols derived from CuAAC reaction between N-propargylAminocyclitol 4 and a series of azides [1−25] is described and tested against GCase. Azides have been chosen from a large collection of potential candidates that has been filtered according to physical and reactivity constraints. A synthetic methodology has been optimized in order to avoid the use of protecting groups on the Aminocyclitol scaffold. Because the reaction can be carried out in an aqueous system, the resulting library members can be screened in situ with minimal manipulation. From the preliminary GCase inhibition data, the most potent library members have been individually resynthesized for further biological screening and complete characterization. Some of the library members have shown biochemical data (IC50, Ki, and stabilization ratio) similar or superior to those reported for NNDNJ. Docking studies have been used to postulate ligand−enzyme interactions to account for the experimental results.
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Medicinal chemistry of Aminocyclitols.
Current medicinal chemistry, 2010Co-Authors: Lucía Díaz, Antonio DelgadoAbstract:Aminocyclitols comprise an important group of compounds with remarkable biological activities. From a structural standpoint, Aminocyclitols are amino polyhydroxy cycloalkanes that can be found in nature in several families of natural products. Among them, the aminoglycoside antibiotics, since the discovery of streptomycin, have become particularly relevant at the forefront of the antibacterial treatment. Another group of Aminocyclitols, generally referred to as aminocarbasugars, have been found as key structural components of some families of alkaloids that have evolved as suitable leads for the development of potent glycosidase inhibitors with a vast array of applications in medicinal chemistry, both as therapeutically useful agents as well as valuable pharmacological tools. On the other hand, the Aminocyclitol moiety has been used by medicinal chemists as a versatile scaffold in drug design. Thus, in the antiviral arena, it is found as the key component of several families of carbocyclic nucleoside analogues, designed as metabolically stable surrogates of the natural nucleosides. Finally, in a still relatively unexplored area, some Aminocyclitol derivatives are being used as key components of artificial receptors for which promising applications in drug research can be envisaged. In all cases, the development of the modern regio- and stereoselective synthetic methodologies enables a large variety of stereochemically defined Aminocyclitol analogues in order to study in depth the influence of this moiety on the structure-activity relationships from a given lead.
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Click Chemistry Approach to New N-Substituted Aminocyclitols as Potential Pharmacological Chaperones for Gaucher Disease†
Journal of medicinal chemistry, 2010Co-Authors: Lucía Díaz, Jordi Bujons, Amadeu Llebaria, Josefina Casas, Antonio DelgadoAbstract:New N-alkylAminocyclitols bearing a 1,2,3-triazole system at different positions of the alkyl chain have been prepared as potential GCase pharmacological chaperones using click chemistry approaches. Among them, compounds 1d and 1e, with the shorter spacer (n = 1) between the alkyltriazolyl system and the Aminocyclitol core, were the most active ones as GCase inhibitors, revealing a determinant effect of the location of the triazole ring on the activity. Furthermore, SAR data and computational docking models indicate a correlation between lipophilicity and enzyme inhibition and suggest “extended” and “bent” potential binding modes for the compounds. In the “bent” mode, the most active compounds could establish a hydrogen-bond interaction between the triazole moiety and enzyme residue Q284. Such an interaction would be precluded in compounds with a longer spacer between the triazole and the Aminocyclitol core.
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recent advances in the chemistry of Aminocyclitols eur j org chem 23 2008
European Journal of Organic Chemistry, 2008Co-Authors: Antonio DelgadoAbstract:The cover picture shows three different approaches to the synthesis of Aminocyclitols. Aminocyclitols are found as structural components of several families of natural products with different biological properties. Several synthetic strategies for this kind of compounds have been devised over the last years. Interestingly, some synthetic Aminocyclitols show interesting properties as glucosidase inhibitors. This is the case for voglibose, a drug marketed as an oral antidiabetic drug and whose three-dimensional structure is shown in the background. Details are presented in the Microreview by A. Delgado on p. 3893 ff.
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Recent Advances in the Chemistry of Aminocyclitols
European Journal of Organic Chemistry, 2008Co-Authors: Antonio DelgadoAbstract:Aminocyclitols are a group of natural products with remarkable biological activities. Over the last years, significant efforts have been made to develop synthetic methodologies directed not only towards their total synthesis but also towards the design of structural analogues with improved or novel biological properties. The aim of this review is to provide the reader with a concise update of the most relevant methods for the synthesis of Aminocyclitols described in the literature. The review is organized according to the methodologies used for the construction of the Aminocyclitol framework. These methodologies include chemoenzymatic approaches, intramolecular cyclizations, reactions of cyclitol derivatives with nitrogen nucleophiles, and rearrangement reactions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Marielle Lemaire - One of the best experts on this subject based on the ideXlab platform.
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Fructose‐1,6‐Bisphosphate Aldolase‐Mediated Synthesis of Aminocyclitols (Analogues of Valiolamine) and their Evaluation as Glycosidase Inhibitors
ChemCatChem, 2009Co-Authors: Lahssen El Blidi, Jean Bolte, Zeinab Assaf, Flora Camps Bres, H Veschambre, Vincent Thery, Marielle LemaireAbstract:A highly stereoselective method for the preparation of nitro- and Aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol reaction of dihydroxyacetone phosphate (DHAP) on hydroxynitrobutanals, is reported. The key part of the synthesis is based on a one-pot /two-enzyme process whereby three reactions take place; rabbit muscle aldolase (RAMA) catalyzed aldolization, phytase-catalyzed phosphate hydrolysis, and intramolecular spontaneous nitroaldolization. Two families of nitrocyclitols were obtained depending on the carbon configuration in the β position to the nitro group. Reduction of the latter afforded the Aminocyclitols. Evaluation of the inhibition properties of the amines towards five commercially available glycosidases has shown selectivity for β-glucosidase and β-galactosidase.
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Straightforward chemo-enzymatic synthesis of new Aminocyclitols, analogues of valiolamine and their evaluation as glycosidase inhibitors.
Tetrahedron: Asymmetry, 2006Co-Authors: Lahssen El Blidi, Mustapha Ahbala, Jean Bolte, Marielle LemaireAbstract:An efficient fructose-1,6-bisphosphate aldolase mediated synthesis of new Aminocyclitol analogues of valiolamine is described. The one-pot process where four stereocentres are created involves the formation of two carbon–carbon bonds. One is catalysed by the aldolase, coupling dihydroxyacetone phosphate to nitrobutyraldehydes. The other is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketones. Depending on the configuration of the hydroxyl which is α to the nitro group, two series of configuration are accessible. The lipase resolution of the nitroalcohol ketal, precursor of the nitroaldehyde, is presented. The inhibition properties of the Aminocyclitols obtained after the reduction of the nitro group are evaluated towards five commercial glycosidases
Xinzhi Chen - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 1 2 3 triazoles from azide derivatised Aminocyclitols by catalytic diazo transfer and cuaac click chemistry
European Journal of Organic Chemistry, 2014Co-Authors: Guoquan Zhou, Chao Qian, Xinzhi ChenAbstract:CuII-catalysed diazo transfer and CuI-catalysed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) “click chemistry” were used to synthesis C7N Aminocyclitol-derivatised 1,2,3-triazoles. In the course of this work, the -N=N- moiety was transferred onto C7N Aminocyclitols such as validamine, valienamine and valiolamine by employing imidazole-1-sulfonyl azide as the diazo transfer reagent with catalysis by CuII, ZnII and NiII, in moderate to good yields. The obtained azidocyclitols were coupled with various terminal alkynes under modified Meldal's conditions with good to excellent yields. The stereo- and regiochemistry of the products were confirmed by 2D-NMR (NOESY and HMBC). One-pot syntheses of the corresponding 1,2,3-triazoles, as safer and more efficient procedures, were also investigated and gave moderate to good yields.
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Synthesis of 1,2,3‐Triazoles from Azide‐Derivatised Aminocyclitols by Catalytic Diazo Transfer and CuAAC Click Chemistry
European Journal of Organic Chemistry, 2014Co-Authors: Guo‐quan Zhou, Chao Qian, Xinzhi ChenAbstract:CuII-catalysed diazo transfer and CuI-catalysed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) “click chemistry” were used to synthesis C7N Aminocyclitol-derivatised 1,2,3-triazoles. In the course of this work, the -N=N- moiety was transferred onto C7N Aminocyclitols such as validamine, valienamine and valiolamine by employing imidazole-1-sulfonyl azide as the diazo transfer reagent with catalysis by CuII, ZnII and NiII, in moderate to good yields. The obtained azidocyclitols were coupled with various terminal alkynes under modified Meldal's conditions with good to excellent yields. The stereo- and regiochemistry of the products were confirmed by 2D-NMR (NOESY and HMBC). One-pot syntheses of the corresponding 1,2,3-triazoles, as safer and more efficient procedures, were also investigated and gave moderate to good yields.