Azetidine Iminosugars from the Cyclization of 3,5-Di-<i>O</i>-triflates of α-Furanosides and of 2,4-Di-<i>O</i>-triflates of β-Pyranosides Derived from Glucose

Primary amines with either 3,5-di-<i>O</i>-ditriflates of α-furanosides or 2,4-di-<i>O</i>-triflates of β-pyranosides form bicyclic azetidines in high yield

Glycosidase Inhibition by All 10 Stereoisomeric 2,5-Dideoxy-2,5-iminohexitols Prepared from the Enantiomers of Glucuronolactone

The enantiomers of glucuronolactone are excellent chirons for the synthesis of the 10 stereoisomeric 2,5-dideoxy-2,5-iminohexitols by formation of the pyrrolidine ring by nitrogen substitution at C2 and C5, with either retention or inversion of configuration; the stereochemistry at C3 may be adjusted during the synthesis to give seven stereoisomers from each enantiomer. A definitive side-by-side comparison of the glycosidase inhibition of a panel of 13 glycosidases showed that 8 of the 10 stereoisomers showed significant inhibition of at least one glycosidase

Synthesis from d‑Altrose of (5<i>R</i>,6<i>R</i>,7<i>R</i>,8<i>S</i>)‑5,7-Dihydroxy-8-hydroxymethylconidine and 2,4-Dideoxy-2,4-imino‑d‑glucitol, Azetidine Analogues of Swainsonine and 1,4-Dideoxy-1,4-imino‑d‑mannitol

Ring closure of a 3,5-di-<i>O</i>-triflate derived from d-altrose with benzylamine allowed the formation of both monocyclic and bicyclic azetidine analogues of swainsonine

<i>C</i>‑Branched Iminosugars: α‑Glucosidase Inhibition by Enantiomers of isoDMDP, isoDGDP, and isoDAB–l‑isoDMDP Compared to Miglitol and Miglustat

The Ho crossed aldol condensation provides access to a series of carbon branched iminosugars as exemplified by the synthesis of enantiomeric pairs of isoDMDP, isoDGDP, and isoDAB, allowing comparison of their biological activities with three linear isomeric natural products DMDP, DGDP, and DAB and their enantiomers. l-IsoDMDP [(2<i>S</i>,3<i>S</i>,4<i>R</i>)-2,4-bis­(hydroxymethyl)­pyrrolidine-3,4-diol], prepared in 11 steps in an overall yield of 45% from d-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases [<i>K</i>_i 0.081 μM for rat intestinal maltase] and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. The partial rescue of the defective F508del-CFTR function in CF-KM4 cells by l-isoDMDP is compared with miglustat and isoLAB in an approach to the treatment of cystic fibrosis