BIOLOGICAL-ACTIVITIES OF THE NORTOPANE ALKALOID, CALYSTEGINE B-2, ANDANALOGS - STRUCTURE-FUNCTION-RELATIONSHIPS

Calystegines, polyhydroxy nortropane alkaloids, are a recently discove red group of plant secondary metabolites believed to influence rhizosp here ecology as nutritional sources for soil microorganisms and as gly cosidase inhibitors. Evidence is presented that calystegines mediate n utritional relationships under natural conditions and that their biolo gical activities are closely correlated with their chemical structures and stereochemistry. Assays using synthetic (+)- and (-)-enantiomers of calystegine B-2 established that catabolism by Rhizobium meliloti, glycosidase inhibition, and allelopathic activities were uniquely asso ciated with the natural, (+)-enantiomer. Furthermore, the N-methyl der ivative of calystegine B-2 was not catabolized by R. meliloti, and it inhibited alpha-galactosidase, but not beta-glucosidase, whereas the p arent alkaloid inhibits both enzymes. This N-methyl analog therefore c ould serve to construct a cellular or animal model for Fabry's disease , which is caused by a lack of alpha-galactosidase activity.