α-Rhamnosidase inhibitory activities of polyhydroxylated pyrrolidine

We designed and synthesized polyhydroxylated pyrrolidines 1–12 from l-tyrosine, l-phenylalanine, and d-tyrosine through iodine-mediated intramolecular cyclization followed by Woodward–Prevost reaction. The synthetic polyhydroxylated pyrrolidines were identified with structure-based inhibitory activity and selective inhibitory activity against α-rhamnosidase. (2S,3S,4R)-deacetyl anisomycin 7 was the best inhibitor among the 12 polyhydroxylated pyrrolidines because it possesses the same stereoconfiguration at C1, C2, C3 as α-l-rhamnopyranoside. An investigation into the nature of the inhibition showed that the synthetic pyrrolidines are competitive inhibitors. They also did not have remarkable inhibitory activity against seven glycosidases (α-glucosidase, α-mannosidase, α-amylase, β-glucosidase, β-galactosidase, β-amylase, and invertase).