Indolizidines natural polyhydroxylated

Figure 6. Some naturally-occurring polyhydroxylated indolizidine alkaloids.

In addition to swainsonine, some of the other naturally-occurring polyhydroxylated alkaloids listed in Table 1 also show various anti-cancer properties. However, none of these compounds have been exploited to nearly the same extent as swainsonine. For example, the potent a-glucosidase inhibitor castanospermine (also an indolizidine alkaloid) has been reported to inhibit experimental metastasis in mice. ... 

During 1993, Daly and co-workers reviewed the alkaloids found in amphibians [5] and Takahata et al. focused on structural assignments and the synthesis of amphibian and polyhydroxylated indolizidines [6]. Wink reviewed the characterisation, natural distribution and biological activity of lupine alkaloids [7] and systematic updates on indolizidine and quinolizidine alkaloids are annually summarized by Michael [8-14]. 

Other natural indolizidine alkaloids comprise the fungi indolizidines (slaffamine type alkaloids), Fig. (18), polyhydroxylated indolizidines (usually isolated from the plant genera Eleocarpus, Astragalus and Iponuga), and marine type indolizidines. 

Synthesis of (—)-Laulimalide. Different approaches to the (3-hydroxy sulfone moiety needed for the olefination reaction are frequently used in the synthesis of natural products. For instance, a very common strategy consists of carbonyl reduction of the corresponding a-ketosulfone followed by reductive elimination. This sequence is employed in the synthesis of polyhydroxylated indolizidine alkaloids (Eq. 121),207 (+)-dihydromevinolin,268 pleraplysillin-1,269 amphidino-lide B,270 and the novel antitumor agent (—)-laulimalide (Eq. 158).271... 

Polyhydroxylated indolizidine alkaloids, due to their biological activity, have attracted considerable synthetic interest. The total synthesis of ( —)-l-qp/-swainsonine (250) from the chiral imine 238 (Scheme 58) and the parallel synthesis of (+ )-2,8,8a-tri-qp/-swainsonine (252) from the enantiomeric threose A-benzylimine 251, prepared from natural L-tartaric acid, provide further examples of the utility of tartaric acid in meeting the challenge of complex syntheses. A stereospecific 4 + 4 homologation utilizing 2-(trimethylsiloxy)furan (178) pro-... 

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. 

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