The Experts below are selected from a list of 405 Experts worldwide ranked by ideXlab platform
Rosa M. De Lederkremer - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of arabinofuranose branched galactofuran tetrasaccharides, constituents of mycobacterial arabinogalactan†
Organic & biomolecular chemistry, 2011Co-Authors: Lucía Gandolfi-donadío, Rosa M. De Lederkremer, Malena Santos, Carola Gallo-rodriguezAbstract:Mycolyl-arabinogalactan (mAG) complex is a major component of the cell wall of Mycobacterium tuberculosis, the causative agent of tuberculosis disease. Due to the essentiality of the cell wall for mycobacterium viability, knowledge of the biosynthesis of the arabinogalactan is crucial for the development of new therapeutic agents. In this context, we have synthesized two new branched arabinogalactafuranose tetrasaccharides, decenyl β-D-Galf-(1→5)-β-D-Galf-(1→6)[α-D-Araf(1→5)]-β-D-Galf (1) and decenyl β-D-Galf-(1→6)-[α-D-Araf-(1→5)]-β-D-Galf-(1→5)-β-D-Galf (2), as interesting tools for arabinofuranosyl transferase studies. The Aldonolactone strategy for the introduction of the internal D-Galf was employed, allowing the construction of oligosaccharides from the non-reducing to the reducing end. Moreover, a one-pot procedure was developed for the synthesis of trisaccharide lactone 21, precursor of 2, which involved a glycosylation-deprotection-glycosylation sequence, through the use of TMSOTf as catalyst of the trichloroacetimidate method as well as promoter of TBDMS deprotection.
-
Synthesis of trisaccharides containing internal galactofuranose O-linked in Trypanosoma cruzi mucins
Carbohydrate research, 2009Co-Authors: Verónica M. Mendoza, Rosa M. De Lederkremer, Gustavo A. Kashiwagi, Carola Gallo-rodriguezAbstract:Abstract The trisaccharides β- d -Gal f -(1→2)-β- d -Gal f -(1→4)- d -GlcNAc ( 5 ) and β- d -Gal p -(1→2)-β- d -Gal f -(1→4)- d -GlcNAc ( 6 ) constitute novel structures isolated as alditols when released by reductive β-elimination from mucins of Trypanosoma cruzi (Tulahuen strain). Trisaccharides 5 and 6 were synthesized employing the Aldonolactone approach. Thus, a convenient d -galactono-1,4-lactone derivative was used for the introduction of the internal galactofuranose and the trichloroacetimidate method was employed for glycosylation reactions. Due to the lack of anchimeric assistance on O-2 of the galactofuranosyl precursor, glycosylation studies were performed under different conditions. The nature of the solvent strongly determined the stereochemical course of the glycosylation reactions when the galactofuranosyl donor was substituted either by 2- O -Gal p or 2- O -Gal f .
-
Photoinduced electron-transfer α-deoxygenation of Aldonolactones. Efficient synthesis of 2-deoxy-d-arabino-hexono-1,4-lactone
Carbohydrate research, 2006Co-Authors: Andrea Bordoni, Rosa M. De Lederkremer, Carla MarinoAbstract:Abstract A photoinduced electron-transfer (PET) reaction was used for the deoxygenation at C-2 of Aldonolactones derivatized as 2- O -[3-(trifluoromethyl)benzoyl] or benzoyl esters. By irradiation of different d -galactono- and d -glucono-1,4-derivatives, with a 450 W lamp, using 9-methylcarbazole as photosensitizer, the corresponding 2-deoxy- d - lyxo - and 2-deoxy- d - arabino -hexono-1,4-lactones were efficiently obtained.
-
Synthesis of α-d-Galp-(1→3)-β-d-Galf-(1→3)-d-Man, a Terminal Trisaccharide of Leishmania Type-2 Glycoinositolphospholipids
The Journal of organic chemistry, 2002Co-Authors: Lucía Gandolfi-donadío, Carola Gallo-rodriguez, Rosa M. De LederkremerAbstract:The synthesis of α-d-Galp-(1→3)-β-d-Galf-(1→3)-d-Man, present in the type-2 glycoinositolphospholipids and in the core of the lipophosphoglycan of Leishmania, is described. The glycosyl Aldonolactone approach, followed by reduction of the lactone with diisoamylborane, was utilized for the introduction of the internal galactofuranosyl unit and the trichloroacetimidate method for the O-glycosidation reaction. A high-yield synthesis of the β-d-Galf-(1−3)-d-Man unit, also present in the lipopeptidophosphoglycan of Trypanosoma cruzi, is reported.
-
Synthesis of β-d-Galp-(1→3)-β-d-Galp-(1→6)-[β-d-Galf-(1→4)]-d-GlcNAc, a tetrasaccharide component of mucins of Trypanosoma cruzi
Tetrahedron, 2002Co-Authors: Carola Gallo-rodriguez, Verónica M. Mendoza, M. Agustina Gil‐libarona, Rosa M. De LederkremerAbstract:Abstract The synthesis of free β- d -Gal p -(1→3)-β- d -Gal p -(1→6)-[β- d -Gal f -(1→4)]- d -GlcNAc and the corresponding alditol which has been previously isolated by reductive β-elimination of Trypanosoma cruzi glycoproteins are described. A convergent route was envisioned by condensing an acceptor derivative of β- d -Gal f -(1→4)- d -GlcNAc with a donor derivative of β- d -Gal p -(1→3)- d -Gal p . The trichloroacetimidate method, as well as SnCl 4 -promoted condensation were utilized for the introduction of the galactofuranosyl unit. On the other hand, the glycosyl-Aldonolactone approach, followed by reduction of the lactone with diisoamylborane, and further isomerization to the galactopyranose configuration gave the donor derivative, which was condensed by the trichloroacetimidate method. Moreover, a synthon for the introduction of the β- d -Gal p -(1→3)- d -Gal f unit is described.
Nicole G. H. Leferink - One of the best experts on this subject based on the ideXlab platform.
-
Identification of a Gatekeeper Residue That Prevents *□S
2013Co-Authors: Dehydrogenases From Acting As Oxidases, Nicole G. H. Leferink, Marco W. Fraaije, Henk-jan Joosten, Peter J. Schaap, Andrea Mattevi, Willem J. H. Van BerkelAbstract:The oxygen reactivity of flavoproteins is poorly understood. Here we show that a single Ala to Gly substitution in L-galactono-�-lactone dehydrogenase (GALDH) turns the enzyme into a catalytically competent oxidase. GALDH is an Aldonolactone oxidoreductase with a vanillyl-alcohol oxidase (VAO) fold. We found that nearly all oxidases in the VAO family contain either a Gly or a Pro at a structurally conserved position near the C4a locus of the isoalloxazine moiety of the flavin, whereas dehydrogenases prefer another residue at this position. Mutation of the corresponding residue in GALDH (Ala-113 3 Gly) resulted in a striking 400-fold increase in oxygen reactivity, whereas the cytochrome c reductase activity is retained. The activity of the A113G variant shows a linear dependence on oxygen concentration (k ox � 3.5 � 10 5 M �1 s �1), similar to most other flavoprotein oxidases. The Ala-113 3 Gly replacement does not chang
-
Galactonolactone oxidoreductase from Trypanosoma cruzi employs a FAD cofactor for the synthesis of vitamin C.
Biochimica et biophysica acta, 2011Co-Authors: Elena V. Kudryashova, Nicole G. H. Leferink, Ilse G.m. Slot, Willem J. H. Van BerkelAbstract:Trypanosoma cruzi, the aetiological agent of Chagas' disease, is unable to salvage vitamin C (l-ascorbate) from its environment and relies on de novo synthesis for its survival. Because humans lack the capacity to synthesize ascorbate, the trypanosomal enzymes involved in ascorbate biosynthesis are interesting targets for drug therapy. The terminal step in ascorbate biosynthesis is catalyzed by flavin-dependent Aldonolactone oxidoreductases belonging to the vanillyl-alcohol oxidase (VAO) protein family. Here we studied the properties of recombinant T. cruzi galactonolactone oxidoreductase (TcGAL), refolded from inclusion bodies using a reverse micelles system. The refolded enzyme shows native-like secondary structure and is active with both l-galactono-1,4-lactone and d-arabinono-1,4-lactone. At odd with an earlier claim, TcGAL employs a non-covalently bound FAD as redox-active cofactor. Moreover, it is shown for the first time that TcGAL can use molecular oxygen as electron acceptor. This is in line with the absence of a recently identified gatekeeper residue that prevents Aldonolactone oxidoreductases from plants to act as oxidases.
-
Functional assignment of Glu386 and Arg388 in the active site of L-galactono-γ-lactone dehydrogenase.
FEBS letters, 2009Co-Authors: Nicole G. H. Leferink, Mac Donald F. Jose, Willy A. M. Van Den Berg, Willem J. H. Van BerkelAbstract:Abstract The flavoenzyme l -galactono-γ-lactone dehydrogenase (GALDH) catalyzes the terminal step of vitamin C biosynthesis in plants. Little is known about the catalytic mechanism of GALDH and related Aldonolactone oxidoreductases. Here we identified an essential Glu–Arg pair in the active site of GALDH from Arabidopsis thaliana . Glu386 and Arg388 variants show high K m values for l -galactono-1,4-lactone and low turnover rates. Arg388 is crucial for the stabilization of the anionic form of the reduced FAD cofactor. Glu386 is involved in productive substrate binding. The E386D variant has lost its specificity for l -galactono-1,4-lactone and shows the highest catalytic efficiency with l -gulono-1,4-lactone.
-
Galactonolactone Dehydrogenase Requires a Redox-Sensitive Thiol for Optimal Production of Vitamin C
Plant physiology, 2009Co-Authors: Nicole G. H. Leferink, Esther Van Duijn, Arjan Barendregt, Albert J. R. Heck, Willem J. H. Van BerkelAbstract:The mitochondrial flavoenzyme l-galactono-γ-lactone dehydrogenase (GALDH) catalyzes the ultimate step of vitamin C biosynthesis in plants. We found that recombinant GALDH from Arabidopsis (Arabidopsis thaliana) is inactivated by hydrogen peroxide due to selective oxidation of cysteine (Cys)-340, located in the cap domain. Electrospray ionization mass spectrometry revealed that the partial reversible oxidative modification of Cys-340 involves the sequential formation of sulfenic, sulfinic, and sulfonic acid states. S-Glutathionylation of the sulfenic acid switches off GALDH activity and protects the enzyme against oxidative damage in vitro. C340A and C340S GALDH variants are insensitive toward thiol oxidation, but exhibit a poor affinity for l-galactono-1,4-lactone. Cys-340 is buried beneath the protein surface and its estimated pKa of 6.5 suggests the involvement of the thiolate anion in substrate recognition. The indispensability of a redox-sensitive thiol provides a rationale why GALDH was designed as a dehydrogenase and not, like related Aldonolactone oxidoreductases, as an oxidase.
-
identification of a gatekeeper residue that prevents dehydrogenases from acting as oxidases
Journal of Biological Chemistry, 2009Co-Authors: Nicole G. H. Leferink, Marco W. Fraaije, Henk-jan Joosten, Peter J. Schaap, Andrea Mattevi, Willem J. H. Van BerkelAbstract:The oxygen reactivity of flavoproteins is poorly understood. Here we show that a single Ala to Gly substitution in l-galactono-gamma-lactone dehydrogenase (GALDH) turns the enzyme into a catalytically competent oxidase. GALDH is an Aldonolactone oxidoreductase with a vanillyl-alcohol oxidase (VAO) fold. We found that nearly all oxidases in the VAO family contain either a Gly or a Pro at a structurally conserved position near the C4a locus of the isoalloxazine moiety of the flavin, whereas dehydrogenases prefer another residue at this position. Mutation of the corresponding residue in GALDH (Ala-113 --> Gly) resulted in a striking 400-fold increase in oxygen reactivity, whereas the cytochrome c reductase activity is retained. The activity of the A113G variant shows a linear dependence on oxygen concentration (k(ox) = 3.5 x 10(5) m(-1) s(-1)), similar to most other flavoprotein oxidases. The Ala-113 --> Gly replacement does not change the reduction potential of the flavin but creates space for molecular oxygen to react with the reduced flavin. In the wild-type enzyme, Ala-113 acts as a gatekeeper, preventing oxygen from accessing the isoalloxazine nucleus. The presence of such an oxygen access gate seems to be a key factor for the prevention of oxidase activity within the VAO family and is absent in members that act as oxidases.
Willem J. H. Van Berkel - One of the best experts on this subject based on the ideXlab platform.
-
Identification of a Gatekeeper Residue That Prevents *□S
2013Co-Authors: Dehydrogenases From Acting As Oxidases, Nicole G. H. Leferink, Marco W. Fraaije, Henk-jan Joosten, Peter J. Schaap, Andrea Mattevi, Willem J. H. Van BerkelAbstract:The oxygen reactivity of flavoproteins is poorly understood. Here we show that a single Ala to Gly substitution in L-galactono-�-lactone dehydrogenase (GALDH) turns the enzyme into a catalytically competent oxidase. GALDH is an Aldonolactone oxidoreductase with a vanillyl-alcohol oxidase (VAO) fold. We found that nearly all oxidases in the VAO family contain either a Gly or a Pro at a structurally conserved position near the C4a locus of the isoalloxazine moiety of the flavin, whereas dehydrogenases prefer another residue at this position. Mutation of the corresponding residue in GALDH (Ala-113 3 Gly) resulted in a striking 400-fold increase in oxygen reactivity, whereas the cytochrome c reductase activity is retained. The activity of the A113G variant shows a linear dependence on oxygen concentration (k ox � 3.5 � 10 5 M �1 s �1), similar to most other flavoprotein oxidases. The Ala-113 3 Gly replacement does not chang
-
Galactonolactone oxidoreductase from Trypanosoma cruzi employs a FAD cofactor for the synthesis of vitamin C.
Biochimica et biophysica acta, 2011Co-Authors: Elena V. Kudryashova, Nicole G. H. Leferink, Ilse G.m. Slot, Willem J. H. Van BerkelAbstract:Trypanosoma cruzi, the aetiological agent of Chagas' disease, is unable to salvage vitamin C (l-ascorbate) from its environment and relies on de novo synthesis for its survival. Because humans lack the capacity to synthesize ascorbate, the trypanosomal enzymes involved in ascorbate biosynthesis are interesting targets for drug therapy. The terminal step in ascorbate biosynthesis is catalyzed by flavin-dependent Aldonolactone oxidoreductases belonging to the vanillyl-alcohol oxidase (VAO) protein family. Here we studied the properties of recombinant T. cruzi galactonolactone oxidoreductase (TcGAL), refolded from inclusion bodies using a reverse micelles system. The refolded enzyme shows native-like secondary structure and is active with both l-galactono-1,4-lactone and d-arabinono-1,4-lactone. At odd with an earlier claim, TcGAL employs a non-covalently bound FAD as redox-active cofactor. Moreover, it is shown for the first time that TcGAL can use molecular oxygen as electron acceptor. This is in line with the absence of a recently identified gatekeeper residue that prevents Aldonolactone oxidoreductases from plants to act as oxidases.
-
Functional assignment of Glu386 and Arg388 in the active site of L-galactono-γ-lactone dehydrogenase.
FEBS letters, 2009Co-Authors: Nicole G. H. Leferink, Mac Donald F. Jose, Willy A. M. Van Den Berg, Willem J. H. Van BerkelAbstract:Abstract The flavoenzyme l -galactono-γ-lactone dehydrogenase (GALDH) catalyzes the terminal step of vitamin C biosynthesis in plants. Little is known about the catalytic mechanism of GALDH and related Aldonolactone oxidoreductases. Here we identified an essential Glu–Arg pair in the active site of GALDH from Arabidopsis thaliana . Glu386 and Arg388 variants show high K m values for l -galactono-1,4-lactone and low turnover rates. Arg388 is crucial for the stabilization of the anionic form of the reduced FAD cofactor. Glu386 is involved in productive substrate binding. The E386D variant has lost its specificity for l -galactono-1,4-lactone and shows the highest catalytic efficiency with l -gulono-1,4-lactone.
-
Galactonolactone Dehydrogenase Requires a Redox-Sensitive Thiol for Optimal Production of Vitamin C
Plant physiology, 2009Co-Authors: Nicole G. H. Leferink, Esther Van Duijn, Arjan Barendregt, Albert J. R. Heck, Willem J. H. Van BerkelAbstract:The mitochondrial flavoenzyme l-galactono-γ-lactone dehydrogenase (GALDH) catalyzes the ultimate step of vitamin C biosynthesis in plants. We found that recombinant GALDH from Arabidopsis (Arabidopsis thaliana) is inactivated by hydrogen peroxide due to selective oxidation of cysteine (Cys)-340, located in the cap domain. Electrospray ionization mass spectrometry revealed that the partial reversible oxidative modification of Cys-340 involves the sequential formation of sulfenic, sulfinic, and sulfonic acid states. S-Glutathionylation of the sulfenic acid switches off GALDH activity and protects the enzyme against oxidative damage in vitro. C340A and C340S GALDH variants are insensitive toward thiol oxidation, but exhibit a poor affinity for l-galactono-1,4-lactone. Cys-340 is buried beneath the protein surface and its estimated pKa of 6.5 suggests the involvement of the thiolate anion in substrate recognition. The indispensability of a redox-sensitive thiol provides a rationale why GALDH was designed as a dehydrogenase and not, like related Aldonolactone oxidoreductases, as an oxidase.
-
identification of a gatekeeper residue that prevents dehydrogenases from acting as oxidases
Journal of Biological Chemistry, 2009Co-Authors: Nicole G. H. Leferink, Marco W. Fraaije, Henk-jan Joosten, Peter J. Schaap, Andrea Mattevi, Willem J. H. Van BerkelAbstract:The oxygen reactivity of flavoproteins is poorly understood. Here we show that a single Ala to Gly substitution in l-galactono-gamma-lactone dehydrogenase (GALDH) turns the enzyme into a catalytically competent oxidase. GALDH is an Aldonolactone oxidoreductase with a vanillyl-alcohol oxidase (VAO) fold. We found that nearly all oxidases in the VAO family contain either a Gly or a Pro at a structurally conserved position near the C4a locus of the isoalloxazine moiety of the flavin, whereas dehydrogenases prefer another residue at this position. Mutation of the corresponding residue in GALDH (Ala-113 --> Gly) resulted in a striking 400-fold increase in oxygen reactivity, whereas the cytochrome c reductase activity is retained. The activity of the A113G variant shows a linear dependence on oxygen concentration (k(ox) = 3.5 x 10(5) m(-1) s(-1)), similar to most other flavoprotein oxidases. The Ala-113 --> Gly replacement does not change the reduction potential of the flavin but creates space for molecular oxygen to react with the reduced flavin. In the wild-type enzyme, Ala-113 acts as a gatekeeper, preventing oxygen from accessing the isoalloxazine nucleus. The presence of such an oxygen access gate seems to be a key factor for the prevention of oxidase activity within the VAO family and is absent in members that act as oxidases.
Carola Gallo-rodriguez - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of arabinofuranose branched galactofuran tetrasaccharides, constituents of mycobacterial arabinogalactan†
Organic & biomolecular chemistry, 2011Co-Authors: Lucía Gandolfi-donadío, Rosa M. De Lederkremer, Malena Santos, Carola Gallo-rodriguezAbstract:Mycolyl-arabinogalactan (mAG) complex is a major component of the cell wall of Mycobacterium tuberculosis, the causative agent of tuberculosis disease. Due to the essentiality of the cell wall for mycobacterium viability, knowledge of the biosynthesis of the arabinogalactan is crucial for the development of new therapeutic agents. In this context, we have synthesized two new branched arabinogalactafuranose tetrasaccharides, decenyl β-D-Galf-(1→5)-β-D-Galf-(1→6)[α-D-Araf(1→5)]-β-D-Galf (1) and decenyl β-D-Galf-(1→6)-[α-D-Araf-(1→5)]-β-D-Galf-(1→5)-β-D-Galf (2), as interesting tools for arabinofuranosyl transferase studies. The Aldonolactone strategy for the introduction of the internal D-Galf was employed, allowing the construction of oligosaccharides from the non-reducing to the reducing end. Moreover, a one-pot procedure was developed for the synthesis of trisaccharide lactone 21, precursor of 2, which involved a glycosylation-deprotection-glycosylation sequence, through the use of TMSOTf as catalyst of the trichloroacetimidate method as well as promoter of TBDMS deprotection.
-
Synthesis of trisaccharides containing internal galactofuranose O-linked in Trypanosoma cruzi mucins
Carbohydrate research, 2009Co-Authors: Verónica M. Mendoza, Rosa M. De Lederkremer, Gustavo A. Kashiwagi, Carola Gallo-rodriguezAbstract:Abstract The trisaccharides β- d -Gal f -(1→2)-β- d -Gal f -(1→4)- d -GlcNAc ( 5 ) and β- d -Gal p -(1→2)-β- d -Gal f -(1→4)- d -GlcNAc ( 6 ) constitute novel structures isolated as alditols when released by reductive β-elimination from mucins of Trypanosoma cruzi (Tulahuen strain). Trisaccharides 5 and 6 were synthesized employing the Aldonolactone approach. Thus, a convenient d -galactono-1,4-lactone derivative was used for the introduction of the internal galactofuranose and the trichloroacetimidate method was employed for glycosylation reactions. Due to the lack of anchimeric assistance on O-2 of the galactofuranosyl precursor, glycosylation studies were performed under different conditions. The nature of the solvent strongly determined the stereochemical course of the glycosylation reactions when the galactofuranosyl donor was substituted either by 2- O -Gal p or 2- O -Gal f .
-
Synthesis of α-d-Galp-(1→3)-β-d-Galf-(1→3)-d-Man, a Terminal Trisaccharide of Leishmania Type-2 Glycoinositolphospholipids
The Journal of organic chemistry, 2002Co-Authors: Lucía Gandolfi-donadío, Carola Gallo-rodriguez, Rosa M. De LederkremerAbstract:The synthesis of α-d-Galp-(1→3)-β-d-Galf-(1→3)-d-Man, present in the type-2 glycoinositolphospholipids and in the core of the lipophosphoglycan of Leishmania, is described. The glycosyl Aldonolactone approach, followed by reduction of the lactone with diisoamylborane, was utilized for the introduction of the internal galactofuranosyl unit and the trichloroacetimidate method for the O-glycosidation reaction. A high-yield synthesis of the β-d-Galf-(1−3)-d-Man unit, also present in the lipopeptidophosphoglycan of Trypanosoma cruzi, is reported.
-
Synthesis of β-d-Galp-(1→3)-β-d-Galp-(1→6)-[β-d-Galf-(1→4)]-d-GlcNAc, a tetrasaccharide component of mucins of Trypanosoma cruzi
Tetrahedron, 2002Co-Authors: Carola Gallo-rodriguez, Verónica M. Mendoza, M. Agustina Gil‐libarona, Rosa M. De LederkremerAbstract:Abstract The synthesis of free β- d -Gal p -(1→3)-β- d -Gal p -(1→6)-[β- d -Gal f -(1→4)]- d -GlcNAc and the corresponding alditol which has been previously isolated by reductive β-elimination of Trypanosoma cruzi glycoproteins are described. A convergent route was envisioned by condensing an acceptor derivative of β- d -Gal f -(1→4)- d -GlcNAc with a donor derivative of β- d -Gal p -(1→3)- d -Gal p . The trichloroacetimidate method, as well as SnCl 4 -promoted condensation were utilized for the introduction of the galactofuranosyl unit. On the other hand, the glycosyl-Aldonolactone approach, followed by reduction of the lactone with diisoamylborane, and further isomerization to the galactopyranose configuration gave the donor derivative, which was condensed by the trichloroacetimidate method. Moreover, a synthon for the introduction of the β- d -Gal p -(1→3)- d -Gal f unit is described.
Inge Lundt - One of the best experts on this subject based on the ideXlab platform.
-
Synthetically Useful Base-Induced Rearrangements of Aldonolactones
Topics in Current Chemistry, 2001Co-Authors: Inge Lundt, Robert MadsenAbstract:Aldonolactones can be activated at the α and ω positions by selective bromination or tosylation. The activated Aldonolactones can be transformed into epoxyAldonolactones by treatment with base under non-aqueous conditions. Treatment of epoxy- or bromodeoxyAldonolactones with aqueous base gives epoxyaldonates in which the epoxide can undergo Payne rearrangement to more stable epoxyaldonates. These can subsequently be opened by the carboxylate group with inversion of the configuration at the attacked carbon. Using this method a number of less available Aldonolactones/acids have been prepared, in a reaction sequence where the configuration at one, two or three carbon centers has been stereospecifically interconverted. An attractive synthesis of L-gluconic acid from D-gluconolactone is presented.
-
Aldonolactones as chiral synthons
Glycoscience Synthesis of Substrate Analogs and Mimetics, 1997Co-Authors: Inge LundtAbstract:This article focusses on the synthetic potential of selectively activated Aldonolactones. These are obtained without using any protection group strategy, thus avoiding one of the less attractive features usually associated with polyhydroxylated compounds. The selectively brominated as well as the sulfonylated lactones are suitable starting materials for the preparation of hydroxylated and amino substituted pyrrolidines and piperidines, obtained by simple treatment with ammonia. Boiling in water transformed the activated lactones into hydroxylated tetrahydrofurans. Radical-initiated internal ring closure of brominated Aldonolactones with unsaturation yields functionalized cyclopentanes regio- and stereospecifically. This results in the synthesis of optically pure carbasugars. Easy manipulation of the hydroxy groups in the cyclopentane-lactones obtained gives access to other hydroxy/amino substituted cyclopentanes.
-
Deoxyiminoalditols from Aldonolactones--V. Preparation of the four stereoisomers of 1,5-dideoxy-1,5-iminopentitols. Evaluation of these iminopentitols and three 1,5-dideoxy-1,5-iminoheptitols as glycosidase inhibitors.
Bioorganic & medicinal chemistry, 1996Co-Authors: Michael Anders Godskesen, Inge Lundt, Robert Madsen, Bryan WinchesterAbstract:The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding Aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-amino-5-deoxy-1,5-lactams, 2, 8, 12 and 17, respectively. Reduction of the lactam function using sodium borohydride/acetic or trifluoroacetic acid, or borane dimethyl sulfide complex yielded the iminopentitols. The compounds 3, 9, 13 and 18, together with the three 1,5-dideoxy-1,5-iminoheptitols 19,20 and 21 were tested for inhibition of the glycosidase activities present in an extract from human liver. Compound 18 was a potent and 19 a moderately good inhibitor of beta-glucosidase. Compound 3 together with 19, 20 and 21, all having D-arabino-configuration at the hydroxy-substituted carbon atoms, were good inhibitors of alpha-L-fucosidase.
-
Selectively tosylated Aldonolactones as precursors for highly functionalized, enantiomerically pure tetrahydrofurans
Tetrahedron, 1995Co-Authors: Holger Frank, Inge LundtAbstract:Abstract α , ω -Di- O -tosylated-Aldonolactones were selectively converted into functionalized tetrahydrofurans when boiled in water-dioxane. Thus, the 2,7-di- O -tosyl-D- glycero -D- gulo -heptono-1,4-lactone ( 1 ) readily gave the 2,5;4,7-di-anhydride with inversion of the configuration at C-2, while the 2,6-di- O -tosylated hexonolactones with D- talo -( 2 )- and D- manno - ( 3 ) configurations gave the 2- O -tosylated 3,6-anhydrides 7 and 9 , respectively. Finally, in a more slow reaction, the 2- O -tosylated-L-rhammono-1,4-lactone ( 4 ) gave the 2,5-anhydride 10 , inverted at C-2, as the only product.
-
ENANTIOMERICALLY PURE, HIGHLY FUNCTIONALIZED TETRAHYDROFURANS FROM SIMPLE CARBOHYDRATE PRECURSORS
Tetrahedron, 1994Co-Authors: Inge Lundt, Holger FrankAbstract:Abstract 6-Bromo-6-deoxy-1,4-Aldonolactones and 6-bromo-6-deoxy-alditols with D-galacto-, D-altro-, D-manno-and D-ido-configuration were selectively converted into hydroxylated tetrahydrofuran derivatives by simple heating in water. The 6-bromo-6-deoxy-D-altritol (10) and 6-bromo-6-deoxy-D-iditol (25) reacted even at room temperature. Likewise, the 6-bromo-2,6-dideoxy-Aldonolactones with D-arabino- (29) and D-lyxo-configuration (31) gave the corresponding 2-deoxy-3,6-anhydrides, when heated in water. The rate of formation of the furan ring by intramolecular nucleophilic substitution was determined by the conformation of the bromopolyols in water.
