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Due in large part to their unmatched structural complexity and unique ability to perturb biological pathways, natural products have historically served as excellent starting points in the drug discovery process. However, in many instances natural products lack the appropriate selectivity or drug-like properties to be useful as chemical probes or treatments for disease. Research in the Riley Group focuses on addressing these issues by applying the techniques of modern synthetic and medicinal chemistry to access natural products and their structural derivatives. These molecules are employed to gain a better understanding of how they interact with their macromolecular targets so we can improve their activity, physiochemical properties, and pharmacokinetic properties. In doing so, we look to not only answer important biological questions but ultimately provide new treatment options for several disease areas related to chronic pain, addiction, and other CNS disorders.