Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones. Issue 24 (8th May 2019)

• Record Type: Journal Article
• Authors: Lazzarotto, Mattia; Hammerer, Lucas; Hetmann, Michael; Borg, Annika; Schmermund, Luca; Steiner, Lorenz; Hartmann, Peter; Belaj, Ferdinand; Kroutil, Wolfgang; Gruber, Karl; Fuchs, Michael
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 24(2019)
• Page Start: 8226
• Page End: 8230
• Publication Date: 2019-05-08
• Subjects: 2-oxoglutarate-dependent dioxygenases -- biocatalysis -- lignans -- podophyllotoxin -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201900926
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Taming iron : Podophyllotoxin and congeners were prepared by chemoenzymatic total synthesis employing the 2‐oxoglutarate‐dependent iron enzyme from Podophyllum hexandrum . The reaction outcome was changed from an enantiodivergent to a kinetic resolution process by substrate engineering. Modifications of the substrate allowed the kinetic resolution of dibenzylbutyrolactones.