Swainsonine, isolation

Colgate, S. M., Dorling, P. R. and Huxtable, C. R. 1979. A spectroscopic investigation of swainsonine an a-mannosidase inhibitor isolated from Swainsona canescens. Austral. J. Chem. 32 2257-2264. 

A trail pheromone of the Pharaoh ant was identified as 3-butyl-5-methylindolizidine of the stereochemistry given in (219) (75JHC289). Slaframine (220) is a metabolite isolated from Rhizoctonia leguminicola responsible for producing excessive salivation in cattle. A stereoselective synthesis was reported (73JOC3848). Swainsonine (221), a potent inhibitor of a-mannosidase, has been isolated from Swainsona caneszens. The stereochemistry was derived from the NMR spectrum (79AJC2257). 

As might be expected for a group of compounds that affect carbohydrate metabolism, the polyhydroxylated alkaloids have been reported to have a wide range of effects on a number of organisms and some cause serious livestock poisonings. In fact, it was the toxicity to livestock of the legumes Swainsona canescens and Castanospermum australe in Australia that first led to the isolation of the toxic principles swainsonine and castanospermine. ... 

Biological applications of swainsonine include the identification of newly isolated mannosidases [63-77], the testing of the importance of glycoproteins in association processes between cells or cellular components [78-86], and the fimction/structure relationship evaluation of many glycoproteins [87-107]. 

Both slaframine and swainsonine were isolated from the fungus Rhizoctonia leguminicula. The fungal infection of red clover hay or pasture is associated with the occurrence of the slobbers syndrome in cattle and horses which consists of excessive salivation (slobbering), lacrimation, feed refusal, bloating, stiff joints, abortion, diarrhoea and/or violent behaviour. Some of these clinical symptoms are similar to loco-weed poisoning but the first two are not observed upon administration of swainsonine to animals [114]. 

Swainsonine has also been isolated in A. lentiginosus in approximately 10-fold greater than in Swainsona canescens [216]. However, in addition... 

Harris et al. postulated that (liS, 8aS)-( + )-l-hydroxyindolizidine (109) and (lf ,8aS)-l-hydroxyindolizidine (110) were pivotal intermediates in the biosynthesis of slafi-amine (3) and swainsonine (cf. Section lU.C) in the fungus Rhizoctonia leguminicola (74). Compound 110 was subsequently isolated as e acetate from extracts of the diablo locoweed. Astragalus oxyphysus (75). 

Very recently, swainsonine was actually isolated in high yield (0.17% by mass) from dried seeds of S. procumbens (97). 

An investigation at Murdoch University into the toxic agent in the Western Australian fabaceous plant, Swainsonia canescens, which causes staggers in horses, led to the isolation of the indolizidine alkaloid swainsonine (95). The symptoms caused by ingestion of this plant were very similar to those observed in another veterinary disorder known to be occasioned by lack of a-mannosida.se, and the Murdoch group was able to show that swainsonine did in fact cause inhibition of this enzyme [112]. 

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