Alkaloids mimicking the structures of monosaccharides are now believed to be widespread in plants and microorganisms, and these sugar mimics inhibit glycosidases because of a structural resemblance to the sugar moiety of the natural substrate. Naturally occurring sugar mimics with a nitrogen in the ring are classified into five structural classes: polyhydroxylated piperidines, pyrrolidines, indolizidines, pyrrolizidines and nortropanes. Glycosidases are involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugates. The realization that alkaloidal sugar mimics might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes has led to increasing interest and demand for these compounds. Most of these effects can be shown to result from the direct or indirect inhibition of glycosidases. The glycosphingolipid (GSL) storage diseases are relatively rare hereditary disorders that are severe in nature and frequently fatal. Possible strategies for the treatment of these lysosomal storage diseases include enzyme replacement therapy, gene therapy and substrate deprivation. Recently, quite a new therapy for lysosomal storage diseases has been reported, namely a ‘chemical chaperone therapy’ for Fabry disease. In this report, the structural basis for the specificity of inhibition of alkaloidal sugar mimics and their current and potential application to biomedical problems will be reviewed.

Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application

Polyhydroxylated alkaloids -- natural occurrence and therapeutic applications.

Indolizidine and quinolizidine alkaloids

Sugars with nitrogen in the ring isolated from the leaves of Morus bombycis

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars.

Two alexines [3-hydroxymethyl-1,2,7-trihydroxypyrrolizidines] from Castanospermum australe

Retention and apparent inversion during azide displacement of α-triflates of 15-lactones

X-ray crystal structure of the hydrochloride of 6-epicastanospermine [(1S,6R,7R,8R,8aR)-1,6,7,8-tetrahydroxy-octahydroindolizine]

The preparation of 3,5-(R)-O-benzylidene-D-glycero-D-gulo-heptono-1,4-lactone, a readily available and powerful chiron, is described; other benzylidene derivatives of heptono-1,4-lactones are characterised. The X-ray crystal structure of 3,5(R):6,7(R)-di-O-benzylidene-D-glycero-D-gulo-heptono-1,4-lactone is reported.

Benzylidene acetals of heptonolactones

Retention and Apparent Inversion During Azide Displacement of α-Triflates of 1,5-Lactones.

Aarti Girdhar

Papers

Two alexines [3-hydroxymethyl-1,2,7-trihydroxypyrrolizidines] from Castanospermum australe

Retention and apparent inversion during azide displacement of α-triflates of 15-lactones

X-ray crystal structure of the hydrochloride of 6-epicastanospermine [(1S,6R,7R,8R,8aR)-1,6,7,8-tetrahydroxy-octahydroindolizine]

Benzylidene acetals of heptonolactones

Retention and Apparent Inversion During Azide Displacement of α-Triflates of 1,5-Lactones.