New routes to indolizidine alkaloids: The total synthesis of (-)-grandisine B

Abstract

The plant family Elaeocarpaceae has been the source of a plethora of structurally related alkaloids isolated over the last 50 years. This Thesis describes our synthetic approaches to (−)-grandisine B I, a bioactive indolizidine alkaloid isolated from Elaocarpus grandis in 2005. An overview of alkaloids isolated from the family Elaeocarpaceae is provided and preliminary studies into the synthesis of grandisine B I are described (Chapters 1 and 2).

Novel routes to bicyclic lactams II and isoquinuclidinone frameworks III have been developed using aqueous ammonia in a one-pot amination/cyclisation sequence (Chapters 3 and 4). The scope of the developed methodology was initially demonstrated with a concise synthesis of the alkaloid (−)-mearsine V. A biomimetic synthesis of (±)-grandisine B I, using the alkaloid grandisine D IV as a synthetic precursor, is then described in Chapter 5.

The development of a formic acid mediated alkyne/acetal cyclisation for the synthesis of heterocyclic scaffolds is also reported. The scope and limitations of the methodology are discussed and applications of the methodology in the synthesis of (−)-grandisine B I and structurally related Elaeocarpus alkaloids are described (Chapter 6).