Synthetic approaches to tremorgenic indoles

The literature on the synthesis of tremorgenic indoles is reviewed in Chapter 1. These compounds are of great importance to agriculture, especially in New Zealand and the United States of America, as they affect the central nervous system of livestock grazing infected pastures. The research centres on the synthesis of lolitrem B, a ten ring structure containing a central indole moiety. The central indole moiety is common for all of the tremorgenic indoles. To this end, studies on the preparation of a trans-fused hydrindane system and its incorporation into the central indole moiety are discussed in Chapter 2. Chapter 3 details investigations into the preparation of a pyrrole from a model used for the hydrindane system. Once obtained, the pyrrole is modified to give the pyranopyrrole, which, in turn, is reacted with dienophiles in Diels-Alder cycloadditions to give substituted indoles. Utilising the model for the hydrindane, studies on the Fischer indole reaction were undertaken to give substituted indoles. Modification of these led to the synthesis of the left-hand side of paspalitrem B. This work is discussed in Chapter 4. Preparation of the tetrahydrofuran portion of lolitrem B and incorporation onto the central indole moiety is detailed in Chapters 3 and 4.