Total synthesis of the 7-3'-linked naphthylisoquinoline alkaloid ancistrocladidine
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
This thesis describes the first total synthesis of ancistrocladidine, a member of the naphthylisoquinoline class of natural products. In Chapter 1 the synthetic challenges presented by the naphthylisoquinoline alkaloids are discussed and strategies that have been adopted in previous syntheses of naphthylisoquinoline alkaloids are overviewed. Chapter 2 identifies 6-alkoxybenzocyclobutenones as useful precursors to the naphthalene core of the naphthylisoquinoline alkaloids. An efficient preparation of 6-alkoxybenzocyclobutenones is developed. Following this, these compounds are utilised in the synthesis of naphthalene building blocks, which are key intermediates in the total synthesis of naphthylisoquinoline alkaloids. Chapter 3 describes the synthesis of functionalised dihydroisoquinoline precursors. Following this, an investigation into the formation of the 7-3' bond is carried out by reaction of the aforementioned intermediates with 6-methoxybenzocyclobutenone, whose synthesis is described in Chapter 2. Unfortunately, the key bond could not be formed using this approach. Following this, Chapter 4 describes an alternative approach to biaryl bond formation that utilises a lead-mediated biaryl coupling. This was used to successfully form the key 7-3'-biaryl bond of ancistrocladidine and the remainder of this chapter describes the completion of an enantioselective total synthesis of the natural product. Chapter 5 summarises the above results and discusses the future potential of this research.