Glycosidase inhibitors from the roots of Glyphaea brevis

Ring‐Junction‐Substituted Polyhydroxylated Pyrrolizidines and Indolizidines from Ketonitrone Cycloadditions

“…The glycosidase inhibitory activity of pyrrolizidines 28 , 29 , and 33 and indolizidine 37 , all of which have a quaternary centre at their ring junction, was investigated next. The inhibition of rice α‐glucosidase, yeast α‐glucosidase, almond β‐glucosidase, Aspergillus niger β‐glucosidase, Aspergillus oryzae β‐galactosidase, jack bean α‐mannosidase, and Aspergillus niger α‐rhamnosidase was evaluated at a 1 m m inhibitor concentration (Table ) . All the compounds were found to inhibit the α‐glucosidases selectively (no significant inhibition of other glycosidases).…”

Allylic Azide Rearrangement in Tandem with Intramolecular Huisgen Cycloaddition for Iminosugar and Glycomimetic Synthesis: Functionalized Piperidine, Pyrrolidine, and Pyrrolotriazoles from d-Mannose

“…Iminosugars, which include piperidines or pyrrolidines 22 with a number of hydroxyl groups are of considerable synthetic, 23 biological and medical interest and a number have already been approved as drugs for use in the clinic. 24 Iminosugars and glycomimetics continue to be investigated for various applications, 25 which include glycosidase inhibition, 26 as pharmacological chaperones 27 or as scaffolds for peptidomimetic design. 28 Taken all together, the further study of the potential of the approach reported herein to generate compounds of biological and medicinal interest is warranted.…”

Synthesis and Structural Revision of Glyphaeaside C

“…While glyphaeaside C was the most potent inhibitor of almond β-glucosidase and snail β-mannosidase out of the isolated compounds, all glyphaeaside alkaloids displayed at least some inhibition of both enzymes seemingly independent of their core configurations. 1 Additionally, glyphaeaside C showed only a mild inhibition of rice α-glucosidase in contrast to similar α-1-C-alkylated derivatives of DNJ, 6 and the A-type glyphaeasidesα-1-C-alkylated derivatives of 1-deoxyfuconojirimycin (DFJ)also lacked the substantial bovine kidney α-L-fucosidase inhibition that is characteristic of similar DFJ derivatives. 7 These structure−activity relationships led to a hypothesis that the side-chain functionalization of the glyphaeasides is the primary determinant of their glycosidase inhibition potency and specificity rather than their iminosugar core configuration.…”

“…The glyphaeaside alkaloids are a family of ten iminosugars that were isolated from the roots of Glyphaea brevis that have polyhydroxylated phenylalkyl side-chains unique among the carbohydrate-like class of natural products (Figure ). Such C -alkylated iminosugars have been found sparingly in nature, being largely limited to the broussonetine family of alkaloids and sporadic occurrences in various plants. − …”