Progress towards the total synthesis of Hibarimicin B and its congeners

Abstract

Hibarimicin B (I) was isolated from a soil sample collected in Hibari, Japan, in 1995, and was identified to be a potent inhibitor of tyrosine kinase via a multi-protein assay. Chapter I of this thesis describes the biological activity of the hibarimicins, in addition to an investigation of the biosynthetic pathway leading to the hibarimicins. Based on this biosynthetic study, we have identified hibarimicinone (II) and HMP-Y1 (III) as key synthetic targets. Chapter II describes a model study investigating the key Hauser annulation for the synthesis of hibarimicinone (II). Synthetic progress towards one of the key intermediates in the synthesis of HMP-Y1 (III) is also presented. Chapter III summarizes the work accomplished to date and provides an overview of the necessary work needed for the total synthesis of hibarimicinone (II) and HMP-Y1 (III).