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

ArticleinBioorganic & Medicinal Chemistry 14(12):4047-54 · July 2006with12 Reads
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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