Synthesis of the C1-C15 Fragment of Incednine

We report on our progress towards the synthesis of the exotic, delicate and tense polyketidic macrolactam of incednine. This work constitutes a significant advancement towards the total synthesis of a family of molecules of biological and medicinal interest. Some of the key features of this synthesis required evolutions from the initially designed strategy, leading to the use of a HWE to build the C2-C9 tetraene. For this purpose, a polyfunctionalized phosphonate was used and obtained through an unprecedented Pd-catalyzed cross-coupling involving the zinc anion of diethyl methylphosphonate. The resulting desired C1-C15 fragment displays a carboxylic acid ester at C1 and a vinyl iodide at C15, both functions being ready for subsequent amide coupling with the C16-C23 fragment and final Suzuki cyclization respectively.