Indoles XIV. 4-Phenylpyrido[4,3-b]indoles and 5-Phenylazepino[4,5-b]indoles by Cyclisation of N-Indolylalkyl-ephedrine Derivatives — Scope and Stereoselectivity

4-Phenyltetrahydropyrido[4,3-b]indoles (1) and 5-phenylhexahydroazepino [4,5-b]indoles (2) were obtained by cyclisation reactions starting from N-3-indolylmethylephedrines and N-3-indolylethylnorephedrines respectively, using conc.sulfuric acid (for 1) and PPA (for 2), the latter cyclisation yielding to the racemised azepinoindoles (2), whereas the previous one reacts to 1 in a remarkably stereoselective manner with double inversion = retention of its configuration, obviously going through a spirocyclic intermediate.Compounds with selectivity to dopamine receptor subtypes can be achieved through rigidification of indolyl-and phenylalkylamines.E.g. the well-known SCH-23390 2 and the recently presented LE 300 3 are molecular combinations of tryptamine and 2-phenylethylamine in a constrained conformation and they proved to be potent and selective D 1 /D 5 -antagonist.Having in mind these structures we focussed our efforts on the synthesis of other partially rigidified indolyl-phenyl-alkylamines such as 1 and 2. Because of the stereogenic centres being of crucial importance for the receptor affinities (see SCH-23390) we decided to use the ephedrine enantiomers, as well as the pseudoephedrine enantiomers as synthons for the phenylethylamine part.