Presented in this talk will be recent progresses in our synthetic studies on a group of natural products possessing complex molecular architectures and potentially useful biological activities. Garsubellin A is a plant-derived meroterpene capable of enhancing the enzyme choline acetyltransferase (ChAT) whose decreased level plays a key role in the symptoms of Alzheimer’s disease. Despite a number of synthetic studies, the absolute stereostructure of garsubellin A had long remained unestablished. We have accomplished the first enantioselective total synthesis of garsubellin A,1 enabling determination of the absolute configuration as well as sustainable preparation of both the natural (–)-garsubellin A and its unnatural (+)-antipode.2 Also performed in our laboratory are synthetic investigations on the marine natural products. The exiguamines are hexacyclic marine alkaloids possessing nanomolar inhibitory activities against indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan metabolism and immune tolerance. Using an approach based on the quinone redox-aromatization process, our synthetic campaign not only achieved efficient total syntheses of the racemic natural products but also allowed access to their enantiomers and diastereomers for biological evaluations.3 Madeirolide A is a marine macrolide isolated from a deep-sea sponge and has been shown to potently inhibit fungal pathogens. In order to address the uncertainty associated with the stereo-structure of madeirolide A, we have undertaken synthetic studies using a modular strategy that provides flexible access to a series of madeirolides with varying stereoisomeric domains.4-6 Discussed will be the results of our studies, how the challenging synthesis problems are addressed by novel approaches, and how the complex synthesis program provides opportunities for explorations of new chemistry and biology.