Year
2004
Degree Name
Doctor of Philosophy (PhD)
Department
Department of Chemistry - Faculty of Science
Recommended Citation
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
Abstract
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.
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.