Abstract
In order to establish a versatile method for the preparation of antiumor benzo [c] phenanthridine alkaloids, the reaction steps from the 2-aryl-1-formamido-1, 2, 3, 4-tetrahydronaphthalenes (2) to the fully aromatized benzo [c] phenanthridine derivatives (5) via the 4b, 10b, 11, 12-tetrahydrobenzo [c] phenanthridines (4) in the Robinson preparative sequence were examined in detail. Bischler-Napieralski reaction of the formamide (2) having an alkoxy group at the para position to the cyclizing point of the 2-phenyl ring substituent gave a mixture of the trans-and cistetrahydrobenzo [c] phenanthridines (4) with or without formation of the 2-aryl-3, 4-dihydronaphthalene derivative (6). There is a limitation in that the presence of the alkoxy group at the para position is required for success in cyclizing the formamide derivative (2). Otherwise, the 2-aryl-3, 4-dihydronaphthalene derivative (6) is the sole product. For the dehydrogenation of the resulting trans-and cis-tetrahydrobenzo [c] phenanthridines (trans-and cis-4) into the fully aromatized product (5), catalytic dehydrogenation with 30% palladium-charcoal in p-cymene and 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) oxidation in the presence of or in the absence of 5% sodium hydroxide aqueous solution were investigated. The catalytic dehydrogenation provided either the desired fully aromatized product (5) or the dihydrobenzo [c] phenanthridine (8). The species of the product depends upon the species of the starting material (4). The DDQ-oxidation gave a variety of results. The mode of product formation seems to be regulated by various factors, including the reaction conditions, the species of substituents of the starting material (4), and the stereochemistry of the starting material (4). The mechanisms of formation of various products are discussed.
