Tetracyclic 13-carboline alkaloids of general structure 1, known as canthines, are of interest due to their broad range of pharmacological activity.1 Of the many such compounds reported in recent years, 2 canthin-6-one
(2) was of particular interest to us because of the imaginative way Snyder and co-workers constructed rings 11 I 1 2
C and D via an intramolecular Diels-Alder reaction. 3 While our own studies in this area led only to the carbocyclic analog of 2, 4 we were mindful of the electrocyclic ring closures of 1-azatrienes used by Hibino 5 and Gilchrist 6 to construct ~/-carbolines and 5,6-dihydro-4H-indolo[3,2,1-ij]napthyridines (3, isocanthines). We now report an efficient route to isocanthin-6-one (4), a new member of this series, in which the key step was an intramolecular hetero Diels-Alder reaction of a l-aza-1,3-diene. 7 3 4
. Indole-3-carboxaldehyde (5) was converted by standard methodologies to 7, the methoxime derivative of 6. Thermal cycloaddition of 7, accompanied by loss of methanol, afforded 4,5-dihydroisocanthin-6-one (8), which was oxidized to 4 by a mixture of palladium and sulfur. The overall route is summarized in Scheme 1; all new compounds were characterized by IR, NMR, and HRMS data.