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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 , chemistry , lignan , hydroxylation , biotransformation , stereochemistry , dioxygenase , ring (chemistry) , enzyme , biocatalysis , organic chemistry , enantioselective synthesis , catalysis , reaction mechanism
Abstract 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.