[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.
Kökösi
J
J
Semmelweis Egyetem, Gyógyszerészi Kémiai Intézet, H-1092 Budapest, Hógyes E. u. 9.
Likó
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Z
Podányi
B
B
Hermecz
I
I
Noszál
B
B
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002243:Carbolines; D007202:Indicators and Reagents