Efficient synthesis from D-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-L-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases

Journal article

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. © 2007 Elsevier Ltd. All rights reserved.

Authors: Rountree, J; Butters, T; Wormald, M; Dwek, R; Asano, N

• Publication status: Published
• Journal: TETRAHEDRON LETTERS
• Volume: 48
• Issue: 24
• Pages: 4287-4291
• Publication date: 2007-06-11
• DOI: 10.1016/j.tetlet.2007.04.041
• ISSN: 0040-4039
• Language: English