Synthesis of alkaloids containing the beta-carboline sub structure.

  • Nigel Lawrance Uttley

Student thesis: Doctoral ThesisPhD


A large number of expected and unexpected compounds have resulted from the study of photolabile beta-carboline enamides. These compounds can be classed as aza-analogues of the hexatriene system and as such undergo similar electrocyclic reactions. Nauclefine (I) (a naturally occurring alkaloid) and isonauclefine (40) (a ring E isomeride of nauclefine) were obtained when the enamide (37) was irradiated with 'soft' ultra-violet light, these isomerides were successfully separated by column chromatography and together with the two other ring E isomerides (prepared by photolysis of corresponding enamides) were tested for activity against the P388lymphocytic leukaemia in mice. Unfortunately none of the four compounds showed any significant activity at reasonable dosage levels. These results indicate that nauclefine is not the component of an extract of the air dried bark of Nauclea parva Merril which is active against the P388lymphocytic leukaemia in mice. This work has stimulated further research at the University of Bath with the plant N. parva in order to ascertain the structure of the compound (s) responsible for its anti-cancer properties. The regiospecific cyclisation of enamides was examined in order to achieve a synthesis of nauclefine which eliminates the careful chromatographic separation of isomers required by the photocyclisation route. Various reports in the literature concerning the photolysis of enamides prompted further study into the stereochemical aspects of the photocyclisation process. A number of compounds were prepared as substrates for photochemical cyclisation and of the form that the stereochemistry of the photolysis products might be deduced. However in the event, oxidation of these products occurred so rapidly that this aim could not be realised. Many of the compounds prepared, in this project required the combined application of various forms of spectroscopy in order that their structures might be determined and therefore no small portion of the work is concerned with the elucidation of spectroscopic problems. The aim of the second part of this thesis was to synthesise the bis-indole alkaloid usambarensine (2). The problem was tackled by considering usambarensine to comprise of the union of two individual compounds (each of which can be classed as an alkaloid in its own right) The two components were prepared without difficulty but the combination of the two proved troublesome inspite of various modifications designed to increase the reactivity of them. Although usambarensine was not synthesised, hopefully the work described in this thesis will enable other researchers to overcome the combination problem.
Date of Award1977
Original languageEnglish
Awarding Institution
  • University of Bath

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