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).

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).

Vinigrol is a structurally unique diterpenoid natural product featuring a tricyclo[4.4.4.0.4a,8a]tetradecene carbon skeleton containing eight contiguous stereocenters and a challenging oxygenation pattern. Vinigrol has been demonstrated to possess a wide array of biological activities including tumor necrosis factor (TNF) antagonism, antihypertensive activity, and platelet aggregation inhibitory activity. Our first-generation plan for the synthesis of vinigrol utilized a cascade reaction sequence involving: (1) diastereoselective alkylation of an α-alkenyl-β-ketoester, (2) retro-aldol-aldol equilibration (3) anion-accelerated oxy-Cope rearrangement, and (4) transannular Dieckmann condensation to afford the bicyclo[5.3.1]undecene ring system of vinigrol in a single operation. Discoveries concerning the limitations of this process are disclosed. Our second-generation approach to vinigrol employed a cis-decalin substrate in an alternative cascade reaction sequence, which was expected to deliver the complete tricyclo[4.4.4.0.4a,8a]tetradecene carbon skeleton of vinigrol in one step. An unexpected deviation from the envisioned reaction pathway instead afforded an alternative tricyclic enol silane. / Chemistry and Chemical Biology