A series of compounds was investigated in order to determine the factors that govern the cycloaromatization reaction exhibited by dynemicin A and related molecules. It was determined that the stereochemistry at C10a dictated the thermal reactivity of compounds equipped with an exo-epoxide. Structures containing an alpha-substituent were unreactive while those possessing a beta-substituent underwent cyclization at 80 degrees C. Molecular mechanics and dynamics calculations indicate that this reactivity difference is due to a steric interaction that develops as the alpha-substituted compounds undergo a conformational change that appears to be necessary for aromatization to occur. Additionally, a C10a alpha-substituted endo-epoxide was synthesized and shown to undergo cycloaromatization under mild acidic conditions via an epoxide opening.