A Diels–Alder Reaction for the Total Synthesis of the Novel Antibiotic Antitumor Agent Mensacarcin

The antibiotic mensacarcin (1), which contains nine stereogenic centers and two epoxy functionalities, is a novel antitumor agent that was first isolated from the culture broth of Streptomyces sp. Gö C4/4 found in a soil sample next to the northern cafeteria of the University of Göttingen. For the synthesis of 1 and related structurally simplified analogs, aDiels–Alder reaction of O‐methyljuglone (11) and the tetrasubstituted 1,3‐butadiene 22 was performed to give the cycloadduct rac‐28, which was transformed into the epoxides rac‐31 and rac‐33. The cytotoxicity of rac‐33 is only 53 times lower than the much more complex 1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)