Towards the total synthesis of RP-66453

This thesis outlines synthetic work towards the total synthesis of RP-66453, a natural product isolated from a strain of Actinomycetes bacteria which has been shown to bind to the neurotensin antagonist of guinea pigs. The synthesis of several analogues of the biaryl ether macrocycle of RP-66453 have been completed via SNAr ring closure. Our approach employed chiral phase transfer catalyst methodology to synthesise unnatural a-amino acids, which allowed us to develop an efficient and concise route to an advanced intermediate on route to RP-66453.Strategies to form the biaryl macrocycle of RP-66453 are also explored using a model substrate. This led us to modify our original strategy and consider using a phenanthrene intermediate as a surrogate of the A-B macrocycle. This could be formed by a radical or photochemically induced transannular ring contraction