Pyrrolizidines natural polyhydroxylated

The pyrrolizidine natural products can be obtained by exploitation of the Petasis MCR for combining aldehydes, amines, and vinylboronic acids, as shown by Pyne and coworkers in 2008 [35]. Application of aldopentoses yields polyhydroxylated allyl amines, that provides opportunity for further derivatization to, for example, uniflorines. The MCR commences by boronate-assisted imine formation and protonation (111). Subsequent alkenyl transfer from the borate to the protonated imine delivers the secondary allyl amine 116 in excellent diastereoselectivity (Scheme 14.14). 

This reaction was applied to the synthesis of natural polyhydroxylated in-dolizidines and pyrrolizidines [179]. For example, (H-)-epiaustralin, which is one of pyrrolizidine alkaloids produced by the plant Castanospermum australe, was synthesized through tandem inter[4 + 2]/intra[3 + 2] cycloaddition of silyl tethered nitroalkene and chiral vinyl ether promoted by MAPh (Scheme 6.151). Furthermore, tandem [4 + 2]/[3 + 2] cycloaddition of nitrocyclopentene and vinyl ether was used as a key step for the synthesis of 1-azafenestranes, a structurally unique family of compounds constructed by four fused cycles (Scheme 6.152) [180]. 

Polyhydroxylated pyrrolizidine alkaloids with a hydroxymethyl substituent at C-3 have been thought to be of very restricted natural occurrence. The alexines and australines have been reported in only two small genera of the Leguminosae (Castanospermum and Alexa). However, a number of such pyrrolizidine alkaloids were found from a quite different family, Hyacinthaceae. In 1999, new polyhydroxylated pyrrolizidines different from... 

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. 

Since 2001, Izquierdo et al. reported a series of syntheses of natural and uimatural polyhydroxylated pyrrolizidine alkaloids and their analogues, including some hyacinthacines. The starting compounds were various protected polyhydroxylated pyrrolidines which were prepared from carbohydrates. A general synthetic pathway using the o-fructose-derived 2,5-dideoxy-2,... 

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