The synthetic challenge of diazonamide A, a macrocyclic indole bis-oxazole marine natural product

The complex structure of the marine metabolite diazonamide A comprises a dichlorinated indole bis- oxazole heteroaromatic fragment, and a [b]-fused dihydrobenzofuran - dihydroindole unit containing an aminal carbon, all incorporated within a strained double macrocyclic array. This review details the synthetic studies on this fascinating natural product starting from early studies on the original structure ( 1991 - 2001), through the synthesis of the originally proposed structure and the subsequent structural revision, to the eventual successful syntheses of the natural product itself. Throughout we focus on the innovative ways in which synthetic chemists have approached the challenges posed by this natural product.