Alternative methods for obtaining of cherylline derivatives

In this book are presented the results from research on alternative approaches towards the synthesis of 4- aryl-l234-tetrhydroisoquinolines as synthetic analogues of the alkaloid cherylline. Optimal conditions for the synthesis of the required 22-disubstituted ethylamine precursors are found. The Schotten- Baumann method for amide synthesis is then successfully applied and the synthesized amides are used in an intramolecular α-amidoalkylation reaction to obtain 4-substituted 1234-tetrahydroisoquinolines. An eco-friendly procedure utilizing PPA/SiO2 catalyst for the intramolecular α -amidoalkylation is developed. Microwave-assisted variant of this eco-friendly procedure is also successfully developed. By the Bischler-Napieralski method are synthesized five new 14- disubstituted-l234-tetrahydroisoquinolines. These are potential inhibitors of DHODH. It is found that the reduction of 14-disubstituted 34-dihydroisoquinolines leads to formation of diastereoisomers. The diastereoisomers are successfully separated by preparative column chromatography and 2:1 (cis:trans) ratio is determined. This ratio is not affected by the temperature at which the reaction is carried out.