| Summary: | <p>This thesis describes attempts to apply the furan oxidative <em>N</em>-spirocyclisation methodology to the synthesis of three alkaloids, namely pandamarilactone-1, lycopladine D and hederacine B.</p> <p>Starting from 5-chloro-1-pentyne, pandamarilactone-1 is synthesised in 10 steps and 9% overall yield. The structure of pandamarilactone-1 is confirmed by HMBC data and sitespecific hydrogen-deuterium exchange in methanol-<em>d</em><sub>4</sub>. Furthermore, the reactivity of pandamarilactone-1 with aqueous ammonia shows that pandamarine is not an experimental artifact from the isolation process and is most likely a genuine natural product.</p> <p>Along the synthetic route towards lycopladine D, the versatile chemistry of a bicyclic enamine is demonstrated by its ability to generate complex multicyclic molecules. A key tricyclic lactam, which is a common structural core found in several other fawcettimine-type <em>Lycopodium</em> alkaloids, is also furnished. The synthesis of the spiro-<em>N,O</em>-acetal and its stereochemistry is also discussed. Furthermore, isotopic labelling studies show that the ammonium ylids of a tricyclic aminoketone intermediate undergo intramolecular Hofmann elimination in preference to Stevens rearrangement. This provides an alternative pathway for tricyclic aminoketone ring expansion to afford bicyclic enones.</p> <p>For the synthesis of hederacine B, a key spirocyclisation precursor is synthesised by dibromocyclopropane electrocyclic ring expansion step followed by intramolecular Heck cyclisation. The regioselectivity of the ring expansion and cycloheptenyl cation capture is controlled using two different approaches. Applying the furan oxidative <em>N</em>-cyclisation methodology, the formal synthesis of 9-<em>epi</em>-hederacine A and 9-<em>epi</em>-hederacine B is completed in 23 and 25 steps, respectively, from Hajos–Parrish ketone.</p>
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