Doctor of Philosophy (PhD)
Department of Chemistry - Faculty of Science
Tang, Minyan,The asymmetric synthesis of polyhydroxylated pyrrolizidine alkaloids, PhD thesis, Department of Chemistry, University of Wollongong, 2004. http://ro.uow.edu.au/theses/233
Chapter 1 of this thesis is a review of the literature on the structure, biological activities and synthesis of polyhydroxylated 3-hydroxymethylpyrrolizidine alkaloids. This Chapter also outlines he aims of this project, which were to develop a flexible synthesis of the 1,2,7-trihydroxy-3-hydroxymethylpyrroizidine alkaloid australine, and its epimers. Chapter 2 describes model synthetic chemical studies on the synthesis of the pyrrolizidine core structure. The key synthetic steps, the aminolysis reaction of vinyl expoxides with ally1 amine, the ring-closing metathesis of the resulting diene, syndihydroxylation of the 2,5-dihydropyrrole product and finally ring closure to give the pyrrolizidine nucleus were successfully developed. Chapter 3 describes the application of the chemistry developed in Chapter 2 to the diastereoselective synthesis of the 3-hydroxymethy1-2,3,5,6,7,7 a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several pyrrolizidine natural products. Two unnatural pyrrolizidine alkaloids, (-)-7-espiaustraline and (+)-1,7-diepiaustraline were successfully synthesized. The oxazolidinone group was found to be a useful protecting group in the RCM reaction and, as part of a pyrrolo[1,2-c]oxazol-3-one ring system, functioned as a stereo- and regio-directing group, in a key diastereoselective syn-dihydroxylation reaction and a regioselective nucleophilic ring-opening of a S,S-dioxo-dioxathiole. Chapter 4 describes the asymmetric synthesis of the pyrrolizidine alkaloid, (+)-1-epiaustraline. Attempts to extend this methodology to the synthesis of australine were not successful since the final pyrrolidine ring closure to produce the desired pyrrolizine was not productive.