Studies towards the total synthesis of asteriscanolide

The cyclooctane sesquiterpene lactone, asteriscanolide 1, has attracted considerable interest in the chemical literature since San Feliciano and colleagues first reported its isolation from Asteriscus aquaticus L. To date, no pharmaceutical applications have been found for 1. However, the challenge offered by the construction of its cyclooctanoid core represents an important target for the development of methods directed towards the preparation of other related eight-membered ring-containing terpenoids with more interesting biological properties. This thesis illustrates an investigation into the total synthesis of natural product asteriscanolide 1. Following up on the previous work established by Marsh,2 an approach to 1 was designed, seeking to build a suitable framework for an intramolecular [3 + 2] nitrile oxide-olefin cycloaddition (INOC) as the pivotal synthetic step to assemble the medium-sized ring. The INOC strategy was extensively investigated. As this remained unsuccessful, the investigation was extended to various other intramolecular strategies, including intramolecular [3 + 2] silyl nitronate-olefin cycloaddition (ISOC), samarium(II) iodide-mediated cyclisation, radical-mediated cyclisation, and nitronate anion-epoxide cyclisation, which identified certain limitations that would hinder further progress. To this end, a second generation towards 1 incorporating ring-closing metathesis (RCM) and intermolecular nitronate anion-epoxide addition was designed. A detail discussion of the results is contained within.