Year
2005
Degree Name
Doctor of Philosophy
Department
Department of Chemistry - Faculty of Science
Recommended Citation
Sengpracha, Waya, Synthesis of biologically active indole-fused heterocyclic derivatives, PhD thesis, Department of Chemistry, University of Wollongong, 2005. http://ro.uow.edu.au/279
Abstract
New synthetic routes to 1,2- and 2,3-fused indoles with seven- or eight-membered rings have been developed in this project, with the longer term aim of assessing their biological activity. Approaches to such fused indole derivatives were accessed via free radical cyclisation from 1- or 2-substituted indole derivatives with haloacetamide precursors. Using 1-substituted indole derivatives with haloacetamide functionalites, free radical cyclisation reactions gave fair yields of the indole- and dihydroindole-fused eight membered ring derivatives. Using 2-substituted indole derivatives with haloacetamide functionalities, prepared in turn by a palladium-mediated cyclisation of N-substituted indoles followed by hydrolysis and subsequent decarboxylation, free radical cyclisation afforded the 7,12-dihydro-indolo[3,2-d]benzazepin-6(5H)-one (Paullone) system in fair yields. A novel synthetic approach to a bis-indole fused seven-membered ring system was developed based on an N-substituted spirooxindole rearrangement. The spiro-indolinols obtained from partial amide reduction underwent rearrangement to give the bis-indole fused seven-membered ring derivatives 270 and 271 under acidic conditions. Antimicrobial activity of the indole fused eight-membered ring systems was evaluated. The compound 5,14-dihydro-10-methoxy-5-methoxy-5-methyindolo[2,1-d][1,5]benzodiazocin-6-one 186c showed by far the most potent antibacterial activity (against Staphylococcus aureus), while 5,14-dihydro-5-(4-methoxybenzyl)indolo[2,1-d][1,5]benzodiazocine-6-one 186d showed good in vitro antimalarial activity against both drug resistant and drug sensitive strains of Plasmodium falciparum. These two compounds represent novel structural leads for such activities.
Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.