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.

We thank the Spanish Ministerio de Ciencia e Innovacion (Grant Nos. CTQ2007-65218 and Consolider Ingenio 2010-CSD-2007-00006 and CTQ2011-24165), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER), and the University of Alicante for generous and continuous financial support.

/pdf/diastereoselective-allylation-of-carbonyl-compounds-and-2yzd9tlqi5.pdf

Diastereoselective allylation of carbonyl compounds and imines: application to the synthesis of natural products.

Indolizidine and quinolizidine alkaloids

http://www.sld.cu/galerias/pdf/sitios/mednat/herbal_medicines_stds_and_aids.pdf

Herbal medicines for sexually transmitted diseases and AIDS.

Isolation from and x-ray crystal structure of alexine, (1r,2r,3r,7s,8s)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine [(2r,3r,4r,5s,6s)-2-hydroxymethyl-1-azabicyclo[3.3.0]octan-3,4,6-triol], a unique pyrrolizidine alkaloid

Janet V. Dring

Papers

Isolation from and x-ray crystal structure of alexine, (1r,2r,3r,7s,8s)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine [(2r,3r,4r,5s,6s)-2-hydroxymethyl-1-azabicyclo[3.3.0]octan-3,4,6-triol], a unique pyrrolizidine alkaloid

Castanospermine in Alexa species

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