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Abstract
The thesis is mainly concerned with the development of synthetic strategies for the synthesis of new heterocyclic systems based on indoles, and which are related to natural products.
A versatile route to indolo[3,2-c]isoquinolines has been found, making use of the acid catalyzed cyclization of indole-3-amides, which in turn were obtained by the Beckmann rearrangement of the related indole-3-oximes. Interestingly, the application of different reaction conditions for the Beckmann rearrangement, lead to the isolation of either the indole-3-amines or indole-3-amides, and these can then be used for further reactions. During an investigation of the scope of this research, a new route for the synthesis of highly substituted indoloimidazole compounds was discovered. These imidazole compounds were formed by an unusual acid catalyzed intermolecular combination of two 2-phenylindole-3-amides.
As part of the continuation of our interest in cyclization reactions, bond formation between nucleophilic indole systems and pendant iminium electrophiles was investigated in a variety of cases. This study led to a ring expansion reaction of 3-substituted-4,6-dimethoxy-2-arylindoles, that generated a range of new benzonaphthyridine derivatives when the indoles and iminium substrates were heated with phosphoryl chloride in acetonitrile. Further research also demonstrated the synthesis of indolobenzodiazepines in good yield by an unusual cyclization reaction. In this case, the initial product of activated 3-arylindoles with 2-acetamidobenzyl chloride was further heated with phosphoryl chloride. In all of this work, the significance of the additional reactivity of indoles provided by the methoxy groups is noteworthy.