Doctor of Philosophy
Department of Chemistry - Faculty of Science
Lindsay, Karl B, The asymmetric synthesis of polyfunctional pyrrolidine alkaloids and their analogues, PhD thesis, Department of Chemistry, University of Wollongong, 2003. http://ro.uow.edu.au/theses/167
The aim of this project was to develop a flexible asymmetric synthesis of 1-aza-[2+n.3.0] bicyclic ring systems (n=1,2,3). This was accomplished by the aminolysis of chiral vinyl epoxides followed by ring closing metathesis of the resulting dienes to give a 2,5-dihydropyrroles. These 2,5-dihydropyrroles were very versatile and could readily be converted to the desired 1-azabicyclic ring structures. Further elaboration to natural products was also possible. To this end the synthesis of the indolizidine alkaloid (-)-swainsonine has been developed via two distinct approaches. Furthermore, the (+)-1,2-di-epi- and (+)-1,2,8-tri-epi-swainsonine analogues were prepared using similar methods. The first example of a trihydroxy-pyrrolo[1,2-a]azepine was also prepared. Our efforts to apply the same synthetic approach to the Stemona alkaloids led to the successful synthesis of a pyrrolo-butyrolactone model system. Attempts to elaborate the same methods to the total synthesis of (+)-croomine, were restricted by the extremly hindered nature of the amino-diene core. Nevertheless the BC ring system of (+)-croomine was constructed, and the synthesis proceeded as far as the triol 334 which was, in principle, only three synthetic steps from (+)-croomine. Regrettably transformation of this advanced intermediate into (+)-croomine could not be achieved in the time available.