Polyketide natural products have drawn attention from the synthetic community due to complex molecular structures and unique biological activities. Polyketides are biosynthesized by numerous species via large polyketide synthases which act as assembly lines to produce large natural products from malonyl- and methylmalonyl-CoA subunits. Accessory domains and post polyketide synthesis tailoring install many oxidative and stereochemically relevant elements necessary for biological activity. The intrinsic stereochemistry about the molecular backbone of the molecules afford distinct conformational preferences which give these large and complex molecules a defined shape.Herein is described the relationship between conformational preference and biological properties of the type-I polyketide natural product GEX1A (herboxidiene). Our laboratory has utilized total synthesis, semi-synthesis, and fermentation of bacterial species to produce the natural products and analogs of the natural product to study the structures and conformational preferences and the respective relationships to biological activity. We utilize these studies to determine new analogs to increase therapeutic potential in future analogs.  The first three chapters of this thesis provide background for Niemann-Pick type C disease, RNA binding molecules and their therapeutic relevance, and analogs of GEX1A and their relationship with biological activity. The compounds present as viable therapeutic agents in several cancers and disease states. This thesis will focus on the biological activity relevant to acute myeloid leukemia and Niemann-Pick type C. Chapter four focuses on the development of structural analogs of GEX1A to study the effects of the 'turn' conformation observed in GEX1A and its relation to observed biological activity. The studies herein explore the structure of GEX1A computationally and experimentally. Total synthesis of two GEX1A conformational analogs has been completed which explore GEX1A's conformational families and the rigidification of the side chain to explore the impact on the 'turn' conformation.