Structural norditerpenoid alkaloids

The MSAL-type alkaloids are potent neuromuscular poisons in mammals, acting at the post-synaptie neuromuseular junction. Variations in structural features of eaeh norditerpenoid alkaloid ean exaeerbate or reduee toxieity. While the mechanism of action of the norditerpenoid alkaloids involves blocking of neuromuscular transmission at the al nicotinic acetylcholine receptors, relative toxicity of individual alkaloids is observed to change with variations in the structural characteristics of the alkaloids (Dobelis et al., 1999). In comparison with the lyeoetonine and MDL-type alkaloids, the high toxicity... 

Structural elucidation of norditerpenoid alkaloids is mostly straightforward since almost all the alkaloids fall in one major skeleton-type and have well defined substitution and configurational pattern. In addition 13C NMR data for norditerpenoid alkaloids is readily available to compare chemical shift data of alkaloids having closely related structures.6,7... 

Similarly it has been shown that the most potent norditerpenoid alkaloids acting as inhibitors of mammalian and insect cholinergic receptors have the C-l 8 anthranilic acid esterification, characteristic of the Delphinium norditerpenoid alkaloid methyllycaconitine (MLA), structurally-related to aconitine [40-42], MLA also had antifeedant effects against Spodoptera eridania with associated post-ingestive and toxic effects at doses within the effective antifeedant dose range of compound 30 [40], suggesting a similar antifeedant mode of action between MLA/aconitine and the C-20 diterpenoid alkaloids. 

The norditerpenoid alkaloids are complex, multi-cyclic Ciq diterpene alkaloids which are highly substituted with hydroxyl, methoxyl and ester groups. These alkaloids occur in members of the Ranunculaceae family (primarily in Aconitum spp. and Delphinium spp.) and many have been determined to be highly toxic to humans and animals. They occur as two skeletal structure types [36,37]. Three structural sub-types are associated with skeletal type 36, based upon C-7 substitution patterns and C-8, C15 unsaturation aconitine type (i.e. aconitine [38]) lycoctonine type (i.e. lycoctonine [36]) and pyrodelphinine type (i.e. pyrodelphinine [39]). Skeletal type 37 is designated the heteratisine type (i.e. heteratisine [37]) norditerpenoid alkaloids (Pelletier et al., 1984). Only a small number of pyrodelphinine and heteratisine type norditerpenoid alkaloids have been characterized and there is very limited toxicity data available for them (Benn and Jacyno, 1983). More than 300 aconitine and lycoctonine norditerpenoid alkaloids have been characterized (Pelletier et al., 1984, 1991). Aconitum spp. contain almost exclusively aconitine type alkaloids while Delphinium spp. contain primarily lycoctonine type with a few aconitine type alkaloids. 

Manners, G. D., Panter, K. E., and Pelletier, S. W. 1995. Structure-Activity Relationships of Norditerpenoid Alkaloids Occurring in Toxic Larkspur Delphinium) Species. Journal of Natural Products 58 863-869. 

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