Meroterpenoids are a highly diverse class of natural products that arise in nature from hybrid terpenoid/non-terpenoid biosynthetic pathways. One highly prevalent motif in many meroterpenoids is the C3-oxidized drimane substructure, which forms the central core of many families including the 3,5-dimethylorsellinic acid-derived fungal meroterpenoids and the sesquiterpenyl indoles. Biosynthetically, this motif is produced through the cyclization of a linear polyisoprene-derived epoxide precursor by various terpene cyclases. Compelling literature evidence has suggested that these enzymes are capable of pre-organizing their respective substrates in specific conformations to generate products with unique ring topologies and stereoconfigurations, which ultimately contribute to the immense structural diversity of the meroterpenoids. Among the possible polycyclization product topologies, the alltrans configuration is the most favored thermodynamically as it allows the fused cyclohexane rings to adopt an all-chair conformation. However, there exists a subset of drimane-containing meroterpenoids that possess alternative ring fusions (Figure ), such as the trans-syn-cis-fusion found in polysin (1) and N-acetyl-polyveoline (2) and the trans-syn-trans-fusion found in the chrodrimanins (e.g., 3 and 4). Access to thermodynamically disfavored ring fusions in these meroterpenoids is made possible by the ability of the respective cyclases to generate the less stable, boat-like transition state during their reactions (Figure ). Such conformational requirements have proven to be prohibitive for synthetic recapitulation as attempts to effect biomimetic cyclizations to prepare trans-synfused drimanes have been met with limited to no success. A synthetic approach towards polyveoline featuring an indoleterminated polyene cyclization failed to overcome the innate thermodynamic preference of the substrate and resulted in exclusive formation of the undesired all-trans product. Though the use of substrates with alternative olefin placement or geometry has garnered some success, these approaches have resulted in either sub-optimal diastereoselectivity or low yields for the desired products.