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.