Synthetic Studies: I. Approaches towards the total synthesis of Chloropeptin I. II. Asymmetric syntheses of (+)- and (-)-oleocanthal. III. Approaches towards the total synthesis of juglorubin

The first chapter focused on approaches towards the total synthesis of anti-HIV agent chloropeptin I. The requisite amino acid building blocks and peptides were synthesized in an enantiocontrolled fashion. Several acyclic peptide backbones were constructed and formation of eastern macrocycle (DEF) of chloropeptin I was studied. A multi-gram scale synthesis of the western macrocycle (BCD) of chloropeptin I was also executed and the effects of amino acid configuration on peptide backbone conformation studied.*; The second chapter described the enantioselective synthesis and assignment of absolute stereochemistry of (-)-oleocanthal, a potent, naturally occurring non-steroidal anti-inflammatory and anti-oxidant agent derived from premium virgin olive oil. Key features of our syntheses entail substrate induced diastereoselective bicyclopentanone alkylation followed by stereoselective Wittig reaction. We have prepared gram quantities of (+)- and (-)-oleocanthals for human oral testing and assigned the absolute stereochemistry to be 3S, 4E. Both syntheses begin with D-(-)-ribose, proceed in 13 steps, and are achieved with an overall yield of 7%.*; The third and final chapter focused on progress towards the total synthesis of juglorubin, which is the first example of a naturally occurring cyclopentadienide anion. After various attempts, an anionic coupling strategy was applied to efficiently couple the western and eastern segments together to form the aromatic backbone of juglorubin. Several unsuccessful approaches, exploring the Nazarov reaction and radical initiated cyclization, were presented to effect the cyclization to cyclopentenone ring. To complete the total synthesis of juglorubin, it remains to form the central cyclopentenone ring, add the two side-chains, and perform the base-induced fragmentation.*; *Please refer to dissertation for diagrams.