Synthetic studies on the taxane diterpenoids
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
This thesis describes synthetic studies aimed towards developing a concise synthesis of taxinine, a member of the taxane class of natural products. In Chapter One, an overview of the strategies used for the synthesis of this class of compounds is provided. A bicyclic enone was identified as a target for the studies described in this thesis. The strategy described also called for the addition of the C-ring by ring-closing metathesis. A six step sequence to a C12-desmethyl A-ring is described in Chapter Two. The key step is the isomerization of an epoxide to an allylic alcohol. It was not possible to extend this chemistry to include C12-methylated substrates. An alternative Diels-Alder approach is also described. This approach allowed the synthesis of a number of C12-methylated A-ring structures. A concise synthesis of diene precursors suitable for exploring the possibility of RCM as a method for the ring closure to form a taxane AB-ring system is described in Chapter Three. The planned ring-closing metathesis reaction was unsuccessful under a number of conditions examined. An investigation described in Chapter Four delineates the use of ring-closing metathesis as a possible method for the introduction of the C-ring onto suitable AB-ring systems. An alternative to the unsuccessful ring-closing metathesis approach, an intramolecular Diels-Alder synthesis of a bicyclo[4.3.1]decene system, is described in Chapter Five. Preliminary investigations into the ring-expansion of this compound are also described. A brief summary and discussion of the future potential of the research conducted in this thesis is provided in Chapter Six.