In this article, we describe further studies toward the originally proposed structure of diazonamide A (1). After confronting a number of failures in synthesizing the heterocyclic core of that structure, success was finally realized through the development of a novel hetero-pinacol-based macrocyclization cascade sequence. Subsequent elaboration led to an advanced compound bearing both of the 12-membered rings of the target molecule. In addition, preliminary biological studies with intermediates and simplified analogues obtained via the developed sequences are also described.