Polyhydroxylated pyrrolizidines

Cycloaddition reaction of nitrone (—)-(394) with dimethyl maleate D14 has been used for the synthesis of two new polyhydroxyl pyrrolizidines (687) and (688) (Schemes 2.293, 2.294). These compounds are analogs of alkaloids ros-marinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)- a-epi-crotanecine) (—)-(688) is a potent and selective inhibitor of a-mannosidases (310). The reaction of (—)-(394) with dimethyl maleate gave a 9.6 6 1 mixture of cycloadducts (—)-(680), (+ )-(680), and (—)-(681), which arise from anti-exo,... 

In 1988, alexine (65), a polyhydroxylated pyrrolizidine alkaloid, was isolated from the pods of legume Alexa Idopetala [56]. Although the broad class of pyrrolizidine alkaloids bear a carbon substituent at C-1 [57,58], alexine is the first example of a pyrrolizidine alkaloid with a carbon substituent at C-3. At about the same time, australine (66) was isolated from the seeds of C. australe and found to be 7a-epi-alexine by X-ray crystallographic analysis [59]. The isolation of 1-epi-australine (67),... 

Figure 19.7 Structure of the polyhydroxylated pyrrolizidines obtained by the chemo-enzymatic scheme. Pase-(Acid phosphatase).

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... 

Other polyhydroxylated pyrrolizidines are the hyacinthacines, named after their occurrence in members of the plant family Hyacinthaceae (Uyacinthoides non-scripta and Scilla campanulata) The stereochemical disposition of substituents around the pyrrolizidine core was determined by nOe effects in the NMR spectra, but the... 

C,H,5N04, Mr 189.21, mp. I62-I63 C, (c]d +40 (H2O). A. is a polyhydroxylated pyrrolizidine alkaloid (see polyhydroxy alkaloids) from the tree Alexa leio-petala, a south American Fabaceae. The 8-epimer aus-... 

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,... 

Moreover, recently the boronic acid Mannich reaction, mostly referred to as Petasis reaction [163,164], has evolved as a powerful entry to polyhydroxylated pyrrolizidine, indol-izidine, and tropane alkaloids, among others [165, 166]. For example, Pyne and coworkers disclosed a short total synthesis of calystegine (270) starting from (-)-o-lyxose in 4.7% overall yield (Scheme 11.55), which involved, besides a ring-closing metathesis, the Petasis reaction as key step [167]. In a similar fashion, castanospermine (86) was prepared in 14 steps from (-)-L-xylose in 1.5% overall yield (Scheme 11.55) [168]. 

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