Title of article :
Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases
Author/Authors :
Rountree، نويسنده , , J.S.Shane and Butters، نويسنده , , Terry D. and Wormald، نويسنده , , Mark R. and Dwek، نويسنده , , Raymond A. and Asano، نويسنده , , Naoki and Ikeda، نويسنده , , Kyoko and Evinson، نويسنده , , Emma L. and Nash، نويسنده , , Robert J. and Fleet، نويسنده , , George W.J.، نويسنده ,
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.
