Total Synthesis of Aetheramide A.

The first total synthesis of the highly potent anti-HIV natural product aetheramide A was accomplished in 18 steps from four equally complex building blocks. The synthesis established the unknown configuration at C26 and used a configurationally labile β-ketoester moiety for the self-adjustment of the configuration at a methyl branch. The pivotal macrolactamization was achieved by trapping a thermally generated acylketene which was derived from its corresponding dioxinone.