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Chemoenzymatic Total Synthesis of Deoxy‐, epi ‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones
Author(s) -
Lazzarotto Mattia,
Hammerer Lucas,
Hetmann Michael,
Borg Annika,
Schmermund Luca,
Steiner Lorenz,
Hartmann Peter,
Belaj Ferdinand,
Kroutil Wolfgang,
Gruber Karl,
Fuchs Michael
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201900926
Subject(s) - podophyllotoxin , kinetic resolution , lignan , chemistry , hydroxylation , biotransformation , stereochemistry , enzyme , ring (chemistry) , biocatalysis , dioxygenase , resolution (logic) , organic chemistry , catalysis , reaction mechanism , enantioselective synthesis , artificial intelligence , computer science
Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy‐, epi ‐, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation and a biocatalytic kinetic resolution of the corresponding dibenzylbutyrolactones with the same 2‐oxoglutarate‐dependent dioxygenase. The reaction can be conducted on 2 g scale, and the enzyme allows tailoring of the initial, “natural” structure and thus transforms various non‐natural derivatives. Depending on the substitution pattern, the enzyme performs an oxidative C−C bond formation by C−H activation or hydroxylation at the benzylic position prone to ring closure.