L-DMDP and L-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from D-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While L-DMDP and L-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.

The first total synthesis of (+)-broussonetine W (4), a naturally-occurring pyrrolidine iminosugar isolated from the traditional Chinese medical plant Broussonetia kazinoki SIEB (Moraceae), has been completed through a concise synthetic route starting from the readily available D-arabinose derived cyclic nitrone 10 in 11 steps and 31% overall yield, with regioselective installation of the α,β-unsaturated ketone functional group by the elimination of HBr from α-bromoketone as the key step. A number of analogs of (+)-broussonetine W (4) with variable side chain length, different polyhydroxylated pyrrolidine core configurations or saturated cyclohexanones have also been prepared to explore the glycosidase inhibition and the preliminary structure–activity relationship of this intriguing class of compounds. Glycosidase inhibition studies identified the natural product (+)-broussonetine W (4) as a selective and potent inhibitor of β-galactosidase (IC₅₀ = 0.03 μM), while its enantiomer was a selective and potent inhibitor of α-glucosidase (IC₅₀ = 0.047 μM). It was found that the configuration of the polyhydroxylated pyrrolidine ring played a key role on their glycosidase inhibitory activities. The length of side chain and α,β-unsaturated ketone functional group also exhibited some effect on their glycosidase inhibition.

A general and efficient method for the synthesis of polyhydroxylated pyrrolizidines and indolizidines has been developed based on the NHC-catalyzed cross-coupling of sugar-derived cyclic nitrones with enals, which afforded the key intermediates, γ-hydroxyl amino esters, in good to excellent yields. Thus, a variety of polyhydroxylated pyrrolizidines and indolizidines have been synthesized and assayed against various glycosidases, which showed that aryl or alkyl substituents at C-7 of pyrrolizidines or at C-8 of indolizidines reduced the potency of the glycosidase inhibition of these bicyclic iminosugars.