In Pursuit of an Elusive Target: Our Kendomycin Story

Martin, Harry J.; Magauer, Thomas; Mulzer, Johann

Strategies and Tactics in Organic Synthesis 2012, 8, 261-289.

Kendomycin is a novel polyketide having a unique quinone methide ansa-structure and an impressive biological profile. In this article, we provide a chronological overview of our synthetic work towards the title compound. The most challenging problem was the ring closure of the strained ansa-macrocycle, which was eventually achieved by ring-closing metathesis or a highly efficient combination of macrolactonization and photo-Fries reaction. Further key steps of the synthesis involved the formation of the densely substituted tetrahydropyran ring by S_N1 type cyclization and the construction of the C13/C14 olefin either by an Ireland–Claisen rearrangement or by a Negishi cross-coupling. The formation of the quinone methide was achieved by oxidation of the corresponding benzofuran in the final step.