Azaphenalene Alkaloids

Lebrun, B. Braekman, J.-C. Daloze, D. Kalushkov, P. Pasteels, J.M. (1999) Isopsylloborine A, a new dimeric azaphenalene alkaloid fi om lacfybird beetles (Coleoptoa Coccinellidae) Tetrahedron Lett., 40, 8115-6. 

Interest in the detection and isolation of quinolizidine alkaloids has been maintained, and Polish chemists have continued their conformational studies, but the highlights of the year are the syntheses of quinolizidine alkaloids of Poran -thera1,2 and a novel synthesis of azaphenalene alkaloids.3... 

In previous Reports the perhydro-9b-azaphenalene alkaloids derived from species of Coccinellidae (ladybird beetles) were discussed in the quinolizidine chapters while those isolated from the Australian shrub Poranthera corymbosa were included in the section devoted to miscellaneous alkaloids. In this Report the two groups of closely related alkaloids are considered together. 

The structures of the azaphenalene alkaloids of Poranthera corymbosa, poran-therine, porantheridine, poranthericine (51), and O-acetylporanthericine (52) and a related quinolizidine were determined by X-ray analysis (Vol. 5 of these Reports). The isolation and characterization of these alkaloids has now been described in full, and the structure of a new base, porantheriline (53), has been established. ... 

FIGURE 12.5 Potential routes toward the azaphenalene alkaloids. 

In the subfamily Chilocorinae, only three species of one tribe (the Chilocorini) have been chemically studied. This has led to the isolation and structure determination of several alkaloids made up of the familiar 2-methylperhydro-9b-azaphenalene skeleton linked to an azaacenaphthylene ring system, which probably has a biogenetic origin similar to that of the former, but a different cyclization pattern (Fig. 3). 

Although the detection and isolation of bicyclic, tricyclic, and tetracyclic quinolizidine alkaloids and stereochemical studies, increasingly aided by X-ray analysis, proceeds apace, the main emphasis this year is on synthesis of the Nuphar, azaphenalene, and phenanthroquinolizidine alkaloids. 

Once again the azaphenalene, Nuphar, and Lythraceae alkaloids are included in this Chapter. Perhaps the most notable achievement of the year is the synthesis of azaphenalenes of ladybird beetles by Ayer and co-workers.Amongst the new alkaloids, the novel pyridone quinoiizidine, mamanine (3) and its tetrahydro-derivative, pohakuline (5) are of special interest. ... 

Indole and isoquinoline alkaloids continue to play a dominant role. The apor-phinoids, comprising proaporphines, aporphines and related dimers, are treated separately, partly in order to reduce the burden on contributors aristolactams and aristolochic acids, which have not been reviewed since 1961, also are discussed in this chapter. This year the quinolizidine alkaloids, including the sesquiterpenoid Nuphar bases and the appropriate Lythraceae alkaloids, as well as azaphenalenes of plant and insect origin are reviewed together. Amaryllidaceae, Erythrina, imidazole, purine and peptide alkaloids are omitted from this volume, but it is expected that the chemistry of these groups covering the period 1974—1976 will be surveyed in Volume 7. 

Porantherin (1) is an alkaloid from the Australian plant Poranthera corymbosa and possesses an interesting tetracyclic skeleton of the 9b-azaphenalene type [167]. In an instructive biomimetic synthesis of 1 developed by Corey [168] the key intermediate (X) was subjected to the following reactions (a) and (b) leading via A to B, which was further transformed to the target molecule 1 ... 

Three 2a-methyl-perhydro-9b-azaphenalenes that constitute defensive substances of ladybird beetles were synthesized recently (cf. Vol. 7, p. 79), and an alternative synthesis has now been described (Scheme 2). The perhydrobora-phenalene (32) that was employed earlier to prepare unsubstituted perhydro-azaphenalenes (cf. Vol. 6, p. 101) was converted into the enamine quaternary ammonium salt (33) and thence into the allylamine (34). The allylamine epoxide was used to prepare ketone (36), which provided an efficient route to precoc-cinellin (35) by means of a Wittig reaction the same ketone was involved in the earlier synthesis of the alkaloid. 

Porantheridine (1188) is included among the simple quinoHzidine alkaloids in this review as it can be viewed as the internal aminal of a hydroxy-quinohzidinium system. It is one of a handful of rare natural products obtained from the AustraHan shmb Poranthera corymbosa (Euphorbiaceae), most of which are 9b-azaphenalenes. Three enantioselective syntheses... 

The azaphenalene core of (-)-hippodamine (267), a defense alkaloid secreted by the ladybird beetle, can be constructed via an asymmetric azaelectrocyclization and subsequent Mannich cyclization (Scheme 11.54) as key steps [161]. 

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