Azafluorenone alkaloids

As mentioned in Section 10.1.2, Padwa and co-workers (40,41) employed the Pummerer reaction to generate and trap isomtinchnones. This group (190,191) has now adapted the intramolecular version of this tactic to the synthesis of several alkaloids of the pyridine, quinolizidine, and clavine classes. In each case, a 2-pyridone serves as the keystone intermediate. For example, Kuethe and Padwa (190) employed this Pummerer reaction of imidosulfoxides that contain tethered iz-bonds in a formal synthesis of the frog alkaloid ( )-pumiliotoxin C. They also used this methodology to synthesize the azafluorenone alkaloid onychine (295) (Scheme 10.42) (191). Generation of the thionium ion 291 under standard... 

The emergence of the azafluorenone alkaloids as a sizable group and the discovery of the azaanthracenes and azahomoaporphines, all represented in Guat-teria, are very new developments. This chapter reviews these novel substances as completely as possible, discusses a small number of structurally unusual though not unprecedented compounds, and also updates the older contributions on the mainline isoquinoline alkaloids insofar as the genus Guatteria is concerned. 

Onychine (135) was first described as a natural product in 1976, when its isolation from Onychopetalum amazonicum (Annonaceae) was reported (83), and its structure was given as 4-methyl-l-azafluoren-9-one (158) on the basis of elemental analysis and high-resolution MS, as well as UV, IR, and H-NMR spectra. As in all the azafluorenone alkaloids discovered to date, the complex UV spectrum is reminiscent of that of fluoren-9-one, and the H-NMR spectrum clearly indicates the presence of a 2,3-disubstituted 4-methylpyridine moiety. The immediate conclusion, therefore, is that onychine is either l-methyl-4-azafluoren-9-one (135) or 4-methyl-l-azafluoren-9-one (158), which is supported by the spectral properties of the secondary alcohol obtained by reduction of the ketone group and of the acetylation and hydrogenolysis products of this... 

Azafluorenone and diazafluoranthene alkaloids, which are biogenetically related to oxoaporphines, usually co-occur in plants of the family Annona-ceae. Cyathocaline (53), C14H11NO4, mp 222-224°, is a new azafluorenone alkaloid isolated from the stem bark of Cyathocalyx zeylanica Champ, ex Hook. f. and Thoms., a species of the Annonaceae endemic to Sri Lanka (50). Its structure was elucidated using spectroscopic techniques and by... 

Cyathocalyx zeylanica Oxoaporphine alkaloids Azafluorenone alkaloid... 

Cyathocaline exhibited moderate but selective activity in our yeast bioassay and also in a cytotoxicity assay against the A-549 human lung carcinoma cell line (Table 11). Three azafluorenone alkaloids have previously been tested for ( otoxic activity and were found to be inactive [53] but one has been reported to have anticandidal activity [54]. 

Wasps produce bioactive polymethyleneamine alkaloids. Bugs (e.g., winter cherry bug) can consume tropane alkaloids (atropine and scopolamine) and convert scopolamine into atropine. Grasshoppers can produce azafluorenone alkaloids and can consume pyrrolizidine alkaloid by evolutionary development of their enzymatic system. Also, crickets, cad-disflies, dragonflies, and damselflies can use alkaloid feed. Their digestion alkaloids is not known in detail. 

Arango GJ, Cortes D, Cassels BK et al (1987) Alkaloids of the Annonaceae. Part 80. Azafluorenones from Oxandra cf. major and biogenetic considerations. Phytochemistry 26 2093-2098... 

This procedure has been expanded to the synthesis of 4-azafluorenone (5H-indeno[l,2-fc]pyridine-5-one) alkaloids, which have significant biological activity (Scheme 4.9). An aldehyde, 1,3-indanedione, aryl ketone, and ammonium acetate are used as reagents. Heating at 120 °C for 6-15 min in a sealed tube and using DMF as solvent proved optimal. 

The alkaloids from the trunk bark of Peruvian Unonopsis spectabilis Diels have been examined along with 7,7 -bis-dehydronoraporphines, the main ones present, there are known oxoaporphines and several azafluorenones (468). Stem bark of the Colombian U. pacifica R.E. Fries contains a 4,5-dioxo-, a 7-OXO-, and a 7-hydroxyaporphine, along with two 7,7 -bis-dehydronor-aporphines (470). 

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