Spirocyclopropyl pyrrolidines as a new series of alpha-L-fucosidase inhibitors

Laboratoire Réactions Sélectives et Applications, Université de Reims Champagne-Ardenne, UMR URCA/CNRS 6519, UFR Sciences, BP 1039, F-51687 Reims Cedex 2, France.
Bioorganic & Medicinal Chemistry (Impact Factor: 2.79). 07/2006; 14(12):4047-54. DOI: 10.1016/j.bmc.2006.02.005
Source: PubMed


Polyhydroxy 4-azaspiro[2.4]heptane derivatives (spirocyclopropyl iminosugars) were prepared in four to six steps from readily available protected aldoses. The key step of the reaction sequence involves a titanium-mediated aminocyclopropanation of glycononitriles with subsequent cyclization. Five new polyhydroxypyrrolidines so-obtained have been evaluated for their ability to inhibit 16 glycosidases. One of them exhibits selective inhibition of alpha-L-fucosidase from bovine kidney (Ki=1.6 microM, competitive).

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