I. Diversity-Optimized Route to the Ergoline Skeleton The ergot alkaloids possess perhaps the greatest diversity of any class of natural products. They show exceptional activity towards dopamine, serotonin, and other monoamine receptors as agonists, antagonists, and partial agonists. Chemically known as ergolines, many are useful in treating such disorders as Parkinson's disease and migraines, and others may potentially find use in the treatment of cancer due to their activity as tyrosine kinase inhibitors. The rich pharmacology of ergolines has spurred the creation of a number of synthetic routes, all of which are lengthy and not optimized for the introduction of diversity. The development of a short library-optimized route to the ergoline skeleton is reported. The route is structured for introduction of diversity late in the synthetic scheme to allow for the ease of a creation of a new synthetic library. A highly functionalized pyridine ring is utilized for the creation of an (indolylmethyl)pyridine structure by a Fischer indole synthesis. Diverse substituents on the phenylhydrazine component thus become incorporated into the indole ring and are carried through the remaining synthetic steps. Immediately following the Fischer reaction, the ergoline skeleton is constructed via a palladium assisted intramolecular cyclization, and in the final steps of the scheme the pyridine ring is modified and reduced. The resulting library of ergolines promises to be an outstanding tool for investigating the pharmacology of neuroreceptors. II. Synthesis of New HCV Inhibitors Hepatitis C virus (HCV) affects millions of people worldwide and has become a major threat to human health. Today, effective treatments are increasingly available, but new therapeutics are needed due to the rapid mutation rate of the virus. A library-optimized route to a class of dihydropyranobenzimidazole inhibitors has recently been published. The inhibitors had earlier been shown to bind to the internal ribosome entry site (IRES) of the viral RNA, preventing initiation of translation. In the current work, new inhibitors are proposed based on the recently reported X-ray crystal structure of the parent compound bound to the IRES. Utilizing the classic Gabriel synthesis and reductive amination, new alkylamino side chains will be produced and introduced late into the synthetic route via a nucleophilic aromatic substitution reaction. The target molecules will then be made available to our collaborators for bioassay, and continuing refinement of side chain substituents is expected to lead to improved binding affinity and selectivity.