Synthetic Investigations towards the Total Synthesis of Neuroprotective Natural Products

Abstract

This thesis describes synthetic work undertaken towards the synthesis of the neuroprotective natural products mescengricin (12), palmyrolide A (13) and sanctolide A (14). Investigations towards the synthesis of mescengricin (12) were initially directed towards cyclisation of diarylamines 175. Attempts were made to elaborate diarylamines 175 with a view to produce the tricyclic α-carboline core of 12 via cyclisation to form the central pyrrole ring. Difficulties effecting the cyclisation of 175 led us to further investigate the electronic properties of the diarylamines 175. Completion of an important model study led to the synthesis of simplified α-carboline (15) by employing the photocyclisation of diarylamine 167. The total synthesis of the macrocyclic N-methyl enamide palmyrolide A (13f) is next reported. This was achieved using of a unique ring closing metathesis (RCM)/olefin isomerisation methodology that installed the key tertiary enamide functionality. With the successful completion of the synthesis of palmyrolide A (13f) an analogous RCM/olefin isomerisation strategy was used to effect the synthesis of the related macrolide sanctolide A (14a).