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Asymmetric Chemoenzymatic Synthesis of (−)‐Podophyllotoxin and Related Aryltetralin Lignans
Author(s) -
Li Jian,
Zhang Xiao,
Renata Hans
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201904102
Subject(s) - podophyllotoxin , chemistry , natural product , lignan , combinatorial chemistry , stereochemistry , anticancer drug , drug , pharmacology , medicine
(−)‐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.