6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          A new and efficient three-step procedure for the synthesis of 1,6-anhydro-α-D-galactofuranose is described. The key step involves the formation of the galactofuranosyl iodide by treatment of per- O-TBS-D-Gal f with TMSI, the selective 6- O-desilylation by an excess of TMSI, and the simultaneous nucleophilic attack of the 6-hydroxy group on the anomeric carbon, with the iodide as a good leaving group. This compound is a good precursor for building blocks for the construction of 1→6 linkages.

          Abstract

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: not found

          Chemistry and biology of galactofuranose-containing polysaccharides.

          The thermodynamically less stable form of galactose-galactofuranose (Galf)-is essential for the viability of several pathogenic species of bacteria and protozoa but absent in this form in mammals, so the biochemical pathways by which Galf-containing glycans are assembled and catabolysed are attractive sites for drug action. This potential has led to increasing interest in the synthesis of molecules containing Galf residues, their subsequent use in studies directed towards understanding the enzymes that process these residues and the identification of potential inhibitors of these pathways. Major achievements of the past several years have included an in-depth understanding of the mechanism of UDP-galactopyranose mutase (UGM), the enzyme that produces UDP-Galf, which is the donor species for galactofuranosyltransferases. A number of methods for the synthesis of galactofuranosides have also been developed, and practitioners in the field now have many options for the initiation of a synthesis of glycoconjugates containing either alpha- or beta-Galf residues. UDP-Galf has also been prepared by a number of approaches, and it appears that a chemoenzymatic approach is currently the most viable method for producing multi-milligram amounts of this important intermediate. Recent advances both in the understanding of the mechanism of UGM and in the synthesis of galactofuranose and its derivatives are highlighted in this review.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Topology and mutational analysis of the single Emb arabinofuranosyltransferase of Corynebacterium glutamicum as a model of Emb proteins of Mycobacterium tuberculosis.

            The cell wall mycolyl-arabinogalactan (AG)--peptidoglycan complex is essential in mycobacterial species, such as Mycobacterium tuberculosis, and is the target of several antitubercular drugs. For instance, ethambutol (EMB) targets AG biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and Mt-EmbB, as well as the single Emb from Corynebacterium glutamicum. Here, we present for the first time an experimental analysis of the membrane topology of Emb. The domain organization clearly positions highly conserved loop regions, like the recognized glycosyltransferase C motif and the hydrophilic C-terminus towards the periplasmic side of the cell. Moreover, the assignment and orientation of hydrophobic segments identified a loop region, which might dip into the membrane and could possibly line a transportation channel for the emerging substrate. Site-directed mutations introduced into plasmid-encoded Cg-emb were analyzed in a C. glutamicumDeltaemb strain for their AG glycosyl composition and linkage analysis. Mutations analyzed did not perturb galactan synthesis; however, D297A produced a dramatically reduced arabinan content and prevented growth, indicating an inactive Emb. A second D298A mutation also drastically reduced arabinan content; however, growth of the corresponding mutant was not altered, indicating a certain tolerance of this mutation in terms of Emb function. A W659L-P667A-Q674E triple mutation in the chain length regulation motif (Pro-motif) resulted in a reduced arabinose deposition in AG but retained all arabinofuranosyl linkages. Taken together, the data clearly define important residues of Emb involved in arabinan domain formation and, for the first time, shed new light on the topology of this important enzyme.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Enhanced conformational sampling of carbohydrates by Hamiltonian replica-exchange simulation.

              Knowledge of the structure and conformational flexibility of carbohydrates in an aqueous solvent is important to improving our understanding of how carbohydrates function in biological systems. In this study, we extend a variant of the Hamiltonian replica-exchange molecular dynamics (MD) simulation to improve the conformational sampling of saccharides in an explicit solvent. During the simulations, a biasing potential along the glycosidic-dihedral linkage between the saccharide monomer units in an oligomer is applied at various levels along the replica runs to enable effective transitions between various conformations. One reference replica runs under the control of the original force field. The method was tested on disaccharide structures and further validated on biologically relevant blood group B, Lewis X and Lewis A trisaccharides. The biasing potential-based replica-exchange molecular dynamics (BP-REMD) method provided a significantly improved sampling of relevant conformational states compared with standard continuous MD simulations, with modest computational costs. Thus, the proposed BP-REMD approach adds a new dimension to existing carbohydrate conformational sampling approaches by enhancing conformational sampling in the presence of solvent molecules explicitly at relatively low computational cost.
                Bookmark

                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Beilstein J Org Chem
                Beilstein J Org Chem
                Beilstein Journal of Organic Chemistry
                Beilstein-Institut (Trakehner Str. 7-9, 60487 Frankfurt am Main, Germany )
                1860-5397
                2014
                21 July 2014
                : 10
                : 1651-1656
                Affiliations
                [1 ]CIHIDECAR-CONICET-UBA, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, Ciudad Universitaria, 1428 Buenos Aires, Argentina, Tel/Fax: +54-11-45763352
                Article
                10.3762/bjoc.10.172
                4143087
                25161723
                ceb0af50-bfee-495b-a685-6b7c3c0f0d75
                Copyright © 2014, Baldoni and Marino; licensee Beilstein-Institut.

                This is an Open Access article under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: ( http://www.beilstein-journals.org/bjoc)

                History
                : 24 February 2014
                : 26 June 2014
                Categories
                Full Research Paper
                Chemistry
                Organic Chemistry

                Organic & Biomolecular chemistry
                1,6-anhydro-α-d-galf,galactofuranosyl iodide,galactofuranosyl precursor,per-tert-butyldimethylsilyl-β-d-galactofuranose

                Comments

                Comment on this article