[Polycyclic aromatic alkaloids. 10. Annonaceous alkaloids with antimycotic activity]

Two strategies towards the synthesis of isomerically pure azafluorenones are described. Cyclization of the aryl nicotinic acid 7 with polyphosphoric acid and subsequent reductive debromination gives 8-methoxyonychine (3) ("method A"). 6-Methoxyonychine (2), an alkaloid from annonaceae, can be prepared by Parham-cyclization of the carboxylic acid 7 or of the ester 6 ("method B"). In an agar-well diffusion assay 2, 3, and onychine (9a) show moderate activity against Candida albicans. 9e has stronger activity, while other azafluorenones are almost inactive. The structurally related azaoxoaporphine alkaloid sampangine (12) has very strong antifungal activity.