Spirocyclopropyl pyrrolidines as a new series of α-l-fucosidase inhibitors

Abstract: 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 α-l-fucosidase from bovine kidney (K i =1.6μM, competitive). [Copyright &y& Elsevier]