Chemistry and Biology of Diazonamide A: First Total Synthesis and Confirmation of the True Structure

With the addition of a tenth ring, the exchange of an oxygen atom for a nitrogen in the heart of the molecule, and a different terminal residue, the revised architecture for diazonamide A (1) provided an even more challenging molecular puzzle for chemical synthesis than its predecessor. In this article, we detail the first successful total synthesis of diazonamide A, an endeavor which not only verified its proper connectivities and established the stereochemistry of its previously unassignable C-37 chiral center, but which also was attended by the development of several new synthetic strategies and tactics.