Polyhydroxylated piperidine alkaloids

Figure 1. Diagram illustrating the common nomenclature for polyhydroxylated piperidine alkaloids, (a) 5-Amino-5-deoxy-D-glucopyranose has the trivial name nojirimycin, (b) 1-deoxynojirimycin (DNJ) is the trivial name for l,5-dideoxy-l,5-imino-D-glucitol and similarly (c) 1-deoxymannojirimycin (DMJ) is the common name for l,5-dideoxy-l,5-imino-D-mannitol.

Figure 4. Some naturally-occurring polyhydroxylated piperidine alkaloids.

The plant alkaloid castanospermine 155 and the related piperidine alkaloid 1-deox-ynojirimicin 160, like several other polyhydroxylated octahydroindolizidines, piperidines and pyrrolidines, are potent glycosidase inhibitors. These nitrogen bases are of considerable interest for the study of biosynthetic processes and, in addition, castanospermine and some of its derivatives may be of clinical value as antineo-plastic agents and as drugs in the treatment of AIDS. 

Additional applications of olefin metathesis shown below in Scheme 49 and 50 are indicative of the extent to which the olefinic moieties in the primary products may be transformed to complex piperidine-containing molecules, such as polyhydroxylated indolizidine alkaloids and... 

Species belonging to the genera Alexa from Amazonia and Castanospermum from Australia contain polyhydroxylated piperidines, pyrrolidines, indolizines and pyrrolizidines. The presence of this related series of alkaloids suggests the original derivation of both genera from a common ancestor thriving on the old South Panagean continent. 

Glycosidase-inhibiting alkaloids from plants are classified into five structural classes polyhydroxylated pyrrolidines, piperidines, indolizidines, pyrrolizidines, and nortropanes. Furthermore, they also occur as the glycosides. This review describes recent studies on isolation, characterization, glycosidase inhibitory activity, and therapeutic application of the sugar-mimicking alkaloids from plants. 

Because they exhibit various fascinating biological activities [1], polyhydroxylated alkaloids that mimic sugar structure arouse a growing interest in the last few years. Naturally occurring iminosugars are classified in five structural families polyhydroxylated pyrrolidines, piperidines, indolizidines, nor-tropanes, and pyrrolizidines (fused pyrrolidines with N at the bridgehead) alkaloids [2]. The pyrrolizidine skeleton with a hydroxyl substituent at C-3 is relatively rare in Nature and appears to be restricted to specific families, while piperidine and pyrrolidine skeleton are conunon in many species. 

Polyhydroxylated Alkaloids. Polyhydroxy derivatives of pyrrolidine, piperidine, and indolizidine alkaloids have recently been isolated from plants and microorganisms. A number of these compounds have shown potent gluco-sidase inhibitory activity and have generated interest because of their ability to inhibit replication of retroviruses. 

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