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Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases |
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| Authors: | JSShane Rountree Terry D Butters Raymond A Dwek Kyoko Ikeda Robert J Nash |
| Institution: | a Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford OX1 3QU, UK b Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK c Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Ishikawa 9201181, Japan d VASTox plc, Institute of Grassland and Environmental Research, Plas Gogerddan, Aberystwyth, Dyfed, Wales SY23 3EB, UK |
| Abstract: | The synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc proceeded in an overall yield of 25%; the enantiomer, 2-acetamido-1,4-imino-1,2,4-trideoxy-d-arabinitol DABNAc, was prepared from l-lyxonolactone. LABNAc and N-benzyl LABNAc are potent non-competitive inhibitors of d-hexosaminidase, whereas N-benzyl DABNAc exhibits weak competitive inhibition of the enzyme; this provides further evidence in support of Asano’s hypothesis that while d-imino sugar mimics inhibit d-glycohydrolases competitively, their l-enantiomers show non-competitive inhibition and in the case of iminofuranoses l-enantiomers are usually more potent inhibitors. |
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