Asymmetric Chemoenzymatic Synthesis of (−)‐Podophyllotoxin and Related Aryltetralin Lignans

(?)‐Podophyllotoxin is one of the most potent microtubule depolymerizing agents and has served as an important lead compound in antineoplastic drug discovery. Reported here is a short chemoenzymatic total synthesis of (?)‐podophyllotoxin and related aryltetralin lignans. Vital to this approach is the use of an enzymatic oxidative C?C coupling reaction to construct the tetracyclic core of the natural product in a diastereoselective fashion. This strategy allows gram‐scale access to (?)‐deoxypodophyllotoxin and is readily adaptable to the preparation of related aryltetralin lignans.