Sceletium-type alkaloids

Although both the Amaryllidaceae and Sceletium-type alkaloids have common biogenetic precursors, further investigations have revealed that the biosyntheses of these two classes of alkaloids are fundamentally different (185). Therefore, the presence of mesembrenone in Narcissus plants is of chemotaxonomic interest because mesembrines seem to be restricted to Aizoaceae-Mesembrylanthemoidaceae (Dicotyledons) (186). The present finding reveals the presence in the Amaryllidaceae of such unexpected alkaloids as those found in some Sceletium species. 

The mood elevating properties of Sceletium tortuosum have been attributed to mesembrine [9], an alkaloid with potent selective serototun (5-HT) re-uptake inhibition activity 86). Other sceletium alkaloids as they are now referred to are mesembrenone, mesembrenol and tortuosamine. The use of mesembrine-type alkaloids was patented 92). Selective serotoiun (5-HT) re-uptake inhibitors (SSRls), like mesembrine, have become important treatments in the therapeutic management of depression 93). Several southern African medicinal plants, in particular Amaryllidaceae, have shown in vitro affinity for serotoiun re-uptake transporters 94,95). Several active alkaloids have been identified from Boophone and Crinum species 95, 96). 

The synthesis of mesembrine-type alkaloids belonging to the Sceletium alkaloid family has been carried out extensively in order to seek a... 

This type of action is found in kanna, or Sceletium expansum and Sceletium tortuosum (Aizoaceae), which have been used by South African shamans from prehistoric times to enhance animal spirits, sparkle the eyes, and to stimulate gaiety. The active constituent of kanna is a serotonin-like alkaloid called mesembrine, which is a potent serotonin re-uptake inhibitor—hence, some potential for the treatment of anxiety and depression however, careful clinical trials must be performed. 

Confalone et al. (85) also made use of an intramolecular cycloaddition step in the construction of a range of tri- and tetracyclic products. Phenyl allyl ethers, of the type shown in Scheme 3.94, underwent dehydrative condensation with the requisite amine to furnish the intermediate ylides, which suffered cycloaddition resulting in 285 and 286 in essentially quantitative yield. The ratio of cis/trans fused products was in the range of 10 1. Such a process has been developed to construct the alkaloid (+ / ) sceletium A4 by reaction of the intermediate 287 with amine 288 via the cycloaddition protocol already developed, followed by further chemical manipulation, in an efficient five step synthesis (Scheme 3.94). 

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