Thomas B Parsons

Publications (11) View all

• Article: Total synthesis of kottamide E.

  Thomas B Parsons, Neil Spencer, Chi W Tsang, Richard S Grainger
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  ABSTRACT: The first synthesis of kottamide E, a marine natural product containing a 5,6-dibromindole linked via a (Z)-enamide to an unusual 1,2-dithiolane-containing amino acid, is reported.
  Chemical Communications 02/2013; · 6.17 Impact Factor
• Article: Synthesis of the trans-hydrindane core of dictyoxetane.

  Benedicte Defaut, Thomas B Parsons, Neil Spencer, Louise Male, Benson M Kariuki, Richard S Grainger
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  ABSTRACT: A concise, stereoselective synthesis of the trans-hydrindane core of the marine natural product dictyoxetane is reported, starting from a Robinson annelation derived bicyclic enone. A phosphorane-mediated, pinacol-like rearrangement of a cis-diol, via a formal 1,2-hydride shift, is used to establish the requisite trans ring junction. (31)P NMR supports the formation of the intermediate phosphorane, generated in situ from the reaction of a diol with Ph(3)PCl(2).
  Organic & Biomolecular Chemistry 05/2012; 10(25):4926-32. · 3.70 Impact Factor
• Article: Inhibition of the pneumococcal virulence factor StrH and molecular insights into N-glycan recognition and hydrolysis.

  Benjamin Pluvinage, Melanie A Higgins, D Wade Abbott, Craig Robb, Ankur B Dalia, Lehua Deng, Jeffrey N Weiser, Thomas B Parsons, Antony J Fairbanks, David J Vocadlo, Alisdair B Boraston
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  ABSTRACT: The complete degradation of N-linked glycans by the pathogenic bacterium Streptococcus pneumoniae is facilitated by the large multimodular cell wall-attached exo-β-D-N-acetylglucosaminidase StrH. Structural dissection of this virulence factor using X-ray crystallography showed it to have two structurally related glycoside hydrolase family 20 catalytic domains, which displayed the expected specificity for complex N-glycans terminating in N-acetylglucosamine but exhibited unexpected differences in their preferences for the substructures present in these glycans. The structures of the two catalytic domains in complex with unhydrolyzed substrates, including an N-glycan possessing a bisecting N-acetylglucosamine residue, revealed the specific architectural features in the active sites that confer their differential specificities. Inhibitors of StrH are demonstrated to be effective tools in modulating the interaction of StrH with components of the host, such as the innate immune system. Overall, new structural and functional insight into a carbohydrate-mediated component of the pneumococcus-host interaction is provided.
  Structure 11/2011; 19(11):1603-14. · 6.35 Impact Factor
• Article: Unique N-glycan moieties of the 66-kDa cell wall glycoprotein from the red microalga Porphyridium sp.

  Oshrat Levy-Ontman, Shoshana Malis Arad, David J Harvey, Thomas B Parsons, Antony Fairbanks, Yoram Tekoah
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  ABSTRACT: We report here the structural determination of the N-linked glycans in the 66-kDa glycoprotein, part of the unique sulfated complex cell wall polysaccharide of the red microalga Porphyridium sp. Structures were elucidated by a combination of normal phase/reverse phase HPLC, positive ion MALDI-TOF MS, negative ion electrospray ionization, and MS/MS. The sugar moieties of the glycoprotein consisted of at least four fractions of N-linked glycans, each composed of the same four monosaccharides, GlcNAc, Man, 6-O-MeMan, and Xyl, with compositions Man(8-9)Xyl(1-2)Me(3)GlcNAc(2). The present study is the first report of N-glycans with the terminal Xyl attached to the 6-mannose branch of the 6-antenna and to the 3-oxygen of the penultimate (core) GlcNAc. Another novel finding was that all four glycans contain three O-methylmannose residues in positions that have never been reported before. Although it is known that some lower organisms are able to methylate terminal monosaccharides in glycans, the present study on Porphyridium sp. is the first describing an organism that is able to methylate non-terminal mannose residues. This study will thus contribute to understanding of N-glycosylation in algae and might shed light on the evolutionary development from prokaryotes to multicellular organisms. It also may contribute to our understanding of the red algae polysaccharide formation. The additional importance of this research lies in its potential for biotechnological applications, especially in evaluating the use of microalgae as cell factories for the production of therapeutic proteins.
  Journal of Biological Chemistry 06/2011; 286(24):21340-52. · 4.77 Impact Factor
• Article: Regioselective dibromination of methyl indole-3-carboxylate and application in the synthesis of 5,6-dibromoindoles.

  Thomas B Parsons, Cédric Ghellamallah, Louise Male, Neil Spencer, Richard S Grainger
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  ABSTRACT: Treatment of methyl indole-3-carboxylate with bromine in acetic acid gives methyl 5,6-dibromoindole-3-carboxylate regioselectively, from which the parent 5,6-dibromoindole can be accessed via a one-pot, microwave-mediated ester hydrolysis and decarboxylation. Application of these building blocks in syntheses of natural and non-natural 5,6-dibromoindole derivatives, including meridianin F and 5,6-dibromo-2'-demethylaplysinopsin, is reported.
  Organic & Biomolecular Chemistry 06/2011; 9(14):5021-3. · 3.70 Impact Factor