[Synthesis of carboline alkaloid analogues]

Hybrid compounds were synthesized combining the structural features of two isomer natural indolalkaloids rutaecarpine (1) and nauclefine (2). These aza-bioisosteric analogues are the first representatives of a new heterocyclic ring system. Two alternative reaction routes were developed for the synthesis of pentacyclic compounds (4, 5) in which the key step is the Fischer indolization of the 6-phenylhydrazono-dipyrido[1,2-a;4,3-d]pirimidine-11-ones. In the case of E-ring substituted derivatives the synthesis was carried out via preparation and chemical transformation of pyrido[1,2-a]pirimidine-4-ones (14, 15) to 2-substituted-3-aza-rutaecarpines (17-20). Finally, the nucleophilic displacement of the chlorine atom of 2-chloro-3-aza-rutaecarpine (18) by dialkylaminoethylamine provided the 2-amino-substituted derivative (20) having improved physico-chemical properties and increased antitumour activity. The new compounds are characterized by UV, IR, 1H, 13C NMR spectroscopy.