This thesis describes the inception design and implementation of stereoselective
desymmetrization reactions in the total synthesis of the natural products pactamycin and
paspaline. In the case of pactamycin the author develops a novel asymmetric Mannich reaction
and symmetry-breaking reduction strategy to enable facile construction of the complex core
architecture in fifteen steps using commercially available materials - the shortest synthesis
to date. He subsequently demonstrates the flexibility of this approach in SAR investigations by
highlighting the preparation of twenty-five unique pactamycin structural congeners. For
paspaline the author develops a biocatalytic desymmetrization strategy that allows the highly
controlled synthesis of core stereochemistry and provides a platform for the development of new
conceptual disconnections in the synthesis of steroid-like natural products. This thesis offers
a valuable resource for students embarking on a PhD in total synthesis.
