Total Synthesis of Nominal Diazonamides-Part 2: On the True Structure and Origin of Natural Isolates

In the preceding communication we described a fully synthetic pathway to the structure proposed for ( )-diazonamide A (1, Scheme 1).[1] This material is not identical to the natural product, which raises the obvious question: What is the true structure of diazonamide A? Herein we provide an answer. In addition, we report that defined synthetic entity 8 induces, with equal potency, a toxic phenotype in cell culture indistinguishable from that produced by natural ( )-diazonamide A. Spectroscopic data for the heterocyclic cores of diazonamides A and B are nearly identical.[2] So when the crystal structure of a p-bromobenzamide derivative of diazonamide B was reported as 3,[2a] the diazonamide A assignment Scheme 1. Initial diazonamide structure assignments.