| Chapter 1 describes a mechanistic investigation of the factors that control stereoselection in the construction of polycyclic products containing 12-oxatricyclo[6.3.1.0 2,7]dodecane ring systems with the Prins--pinacol reaction. Stereoelectronic effects, rather than steric factors, were found to be responsible for the stereoselectivity observed. Additionally, a new molecular reorganization was identified that yields products containing a previously unknown oxygen-bridged 2,6-dithiabicyclo[5.5.0]dodecane ring system; a complex cascade sequence that involves oxocarbenium ion formation, followed by sequential 1,2-sulfur and 1,2-oxygen migrations and eventually an unprecedented 7-membered thio-Prins cyclization terminated by a pinacol shift, is suggested to explain the formation of these products.;In chapter 2, the isolation and potential biosynthetic relationship of the isoindolone alkaloid aspergillin PZ to the larger family of aspochalasin and cytochalasin alkaloids are reviewed. A first-generation total synthesis of (+)-aspergillin PZ is described that employs a Prins--pinacol reaction to construct the 8-oxabicyclo[3.2.1]octane core, and a late-stage intramolecular Diels--Alder cycloaddition. Synthetic (+)-aspergillin PZ, spectroscopically identical to the natural sample, was prepared in 29 linear steps and 0.29% overall yield from racemic 2-methyl-3,4-dihydro-2H-pyran-2-carbaldehyde. An alternative Prins--pinacol cyclization reaction that could improve markedly the efficiency of this synthetic pathway is proposed.;Chapter 3 describes a second-generation total synthesis of (+)-aspergillin PZ that proceeds through enantioenriched intermediates, providing the natural product in 30 linear steps and 0.062% overall yield (unoptimized) from methyl pyruvate. |
