Large-Scale Syntheses of Two Novel Bicyclic Ring Systems: Applications Toward the Construction of Swainsonine and Okadaic Acid

Abstract

The thesis is composed of two parts. The first focuses on synthetic efforts toward the total synthesis of swainsonine, an iminosugar, and was performed in the research laboratories of Professor George A. O'Doherty. Novel methodology was applied toward construction of multiple grams of advanced intermediates. The synthetic design also utilized high atom economy. The synthesis starts from furfural and proceeds through a novel palladium-mediated intramolecular cyc1ization as a key step. Potentially 3 steps remain for completion of the total synthesis. This work will compliment recent non-carbohydrate swainsonine routes.

In the second part of this thesis, the synthesis of the C1S-C27 domain of okadaic acid is accomplished. Several key process improvements were realized which made this route scaleable. A large-scale synthesis was therefore undertaken, and multiple grams of advanced intermediates were produced. This work will aid in construction of novel okadaic acid analogs with improved selectivity/ potency for serine-threonine specific protein phosphatases.