Mesembrenone

Further detail of biosynthesis is that 4 -0-demethylmesembrenone (107) and mesembrenone (108) are efficient precursors for mesembrenol (109) and mesembrine (110) (108) was also recorded as an efficient precursor for mesembranol (109 no 4,5-double bond) (108) was not incorporated into (107), indicating that O-demethylation of (108) does not occur to a significant extent.85 The compounds (107) and (108) lie on the pathway to (109) and (110) most reasonably after sceletenone (106), and the results may be fitted together to give the pathway shown in Scheme 10. 

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). 

Few isolations of mesembrine-type alkaloids have been reported. Two examples are the isolation of amisine (379) (from Hymenocallis arenicola) (183) and of mesembrenol (380) (from Crinum oliganthum) (184) from the Amaryllidaceae family. A third example is the isolation of mesembrenone (381), belonging to the mesembrine group, from the aerial parts of Narcissus palladulus (77) growing in Iberia. The structure was elucidated by spectroscopic and chemical methods (Fig. 22). 

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. 

A tandem sulfide-contraction and Robinson annelation reaction was used for the synthesis of a me-sembrine analog, A -mesembrenone (133). The aryl-substituted thiobutyrolactam (130) was treated with chloromethyl vinyl ketone followed by diisopropylethylamine to afford A -mesembrenone (133) in good yield (Scheme 29). The reaction probably proceeds through initial sulfide contraction to the intermediate vinyl enaminone (131), which tautomerized to the enamine (132) and underwent intramolecular Michael closure to produce (133). 

Four new alkaloids were isolated from this plant and their structures were determined by a combination of spectral and chemical methods. The previously known mesembrenone, mesembrine, and mesembranol were isolated in minor amounts. 

Cherylline (88) is a 4-arylisoquinoline derivative, a group with several potential medicinal properties (80), including a weak acetylcholinesterase inhibitory activity (486). Mesembrenone (90), in turn, is mildly active against Molt 4 lymphoid and non-tumoral fibroblastic LMTK cells (463), has a moderate hypotensive effect on arterial pressure, and interacts slightly with DNA (472,498). 

A. Reaction of Mesembrine and Mesembrenone with Diethyl Azodkarboxylate------ 54... 

With the exception of sceletenone and its close relatives, which will be discussed in Section IV,A,7, the remaining extant members of this subgroup are simple relatives of the four alkaloids mesembrine, mesembrenone, mesembranol, and mesembrenol, and include the known base (—)-mesem-brane, which has been demonstrated to occur in S. namaquense (22). The majority of these bases are either O- or JV-demethylated compounds derived from the four above-mentioned alkaloids discussion of these compounds will be confined to representative examples which illustrate general features of the methods used in the elucidation of their structures. 

The driving force for the rather remarkable transformation of normesembrenone to channaine has to derive in large measure from the stability conferred by the cage-like spiroaminol-hemiacetal system and the intramolecular N—H------0(6) hydrogen bond, because mesembrenone shows no... 

An oxidative pathway leading to the formation of N-demethylmesem-brenone from mesembrenone is indicated by the isolation of A-demethyl-iV-formylmesembrenone (31) (50) from S. strictum. 

Sceletenone (30), C15H17NO2, oil, was isolated after extensive chromatographic purification of the phenolic alkaloid fraction of S. namaquense (27). The structure of this compound was deduced lar ly from spectral and chemical comparisons with mesembrenone. The key features of the structure... 

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