In Pursuit of a Competitive Target: Total Synthesis of the Antibiotic Kendomycin

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

Angewandte Chemie, International Edition (2010), 49, (33), 5614-5626.

Kendomycin is a novel polyketide having a unique quinone methide ansa structure and an impressive biological profile. Herein we provide a chronological overview of the synthetic work towards the title compound. Thus far, over a period of about eight years, eight groups worldwide have published on their synthetic efforts resulting in five total syntheses, one formal synthesis, and a number of fragment syntheses. Most approaches roughly mimic the biogenetic pathway, starting with an aromatic polyphenol subunit to which a polyketide chain is attached. Subsequent key steps include macrocyclization and the formation of the densely substituted tetrahydropyran ring, and then a late-stage oxidation and lactol formation.