Institute of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28/II, 8010, Graz, Austria.
Austrian Centre of Industrial Biotechnology, c/o University of Graz, Graz, Austria.
Angew Chem Int Ed Engl. 2019 Jun 11;58(24):8226-8230. doi: 10.1002/anie.201900926. Epub 2019 May 8.
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.
鬼臼毒素可能是木脂素天然产物中最突出的代表。脱氧鬼臼毒素、表鬼臼毒素和鬼臼毒素都是常用化疗药物的前体，它们是通过相应的二苄基丁内酯的立体发散生物转化和生物催化动力学拆分，用相同的 2-氧戊二酸依赖性双加氧酶制备的。该反应可以在 2 g 规模下进行，并且该酶允许对初始“天然”结构进行定制，从而转化各种非天然衍生物。根据取代模式，该酶通过 C-H 活化或苄位易于环合的位置的羟化作用进行氧化 C-C 键形成。
