Chemoenzymatic Total Synthesis of Deoxy-, epi-, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones
Chemoenzymatic Total Synthesis of Deoxy-, epi-, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones
复制标题
DOI：
10.1002/anie.201900926
复制
发表时间：
2019-06-11
影响因子：
16.6
通讯作者：
Fuchs, Michael
中科院分区：
文献类型：
--
作者：
Lazzarotto, Mattia;Hammerer, Lucas;Fuchs, Michael
鬼臼毒素可能是木脂素类天然产物中最突出的代表。脱氧、表观和鬼臼毒素都是常用化疗药物的前体，它们都是通过立体发散生物转化和生物催化动力学拆分相应的二苄基丁内酮和相同的依赖2-氧戊二酸的双加氧酶而制备的。该反应可以在2克的范围内进行，这种酶可以对初始的“天然”结构进行剪裁，从而转化为各种非天然的衍生物。根据取代模式的不同，酶通过C-H活化或在易于闭环的苄基位置进行羟化来执行氧化C-C键的形成。
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.