Studies towards the total synthesis of 'upenamide

Abstract

Synthetic studies towards the total synthesis of the macrocyclic marine alkaloid ‘upenamide (I) are reported. After an introduction (Chapter 1), Chapter 2 describes an extension of some methodology utilised during the total synthesis project. Both the polycyclic ABC and DE core units of ’upenamide were formed by a stannous chloride dihydrate mediated cyclisation reaction and the methodology described involves using stannous chloride dihydrate to deliver novel polycyclic heterocycles, for example II, III and IV.

In Chapter 3, a shortened synthetic route to the ABC core unit V is described, using a novel azide as a protected amine.

A route to the DE core unit VI was developed and is described in Chapter 4. Chapter 5 describes the coupling of the DE core unit VI with the ABC core unit precursor VII, giving the ABC and DE cores joined through the fully saturated chain in the advanced intermediate VIII. Chapter 5 also contains a discussion of future research needed to complete the program of research into ’upenamide.