Bernhard Laura M, Zelenska Kateryna, Takashima Mirei, Arisawa Mitsuhiro, Murai Kenichi, Gröger Harald
Chair of Industrial Organic Chemistry and Biotechnology, Faculty of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany.
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
J Org Chem. 2024 Jun 21;89(12):8513-8520. doi: 10.1021/acs.joc.4c00459. Epub 2024 Jun 5.
This contribution describes the development of chemoenzymatic one-pot processes, which combine an oxidative rearrangement and a biotransformation catalyzed by an imine reductase (IRED), for the synthesis of highly enantiomerically enriched secondary amines, such as an aryl-substituted pyrrolidine and a benzazepine. The benefits of this chemoenzymatic one-pot approach include high overall conversions (up to >99%), high enantiomeric excesses (up to >99% ), and a straightforward synthetic approach toward secondary amines without the need to isolate the formed intermediate. For the initial chemical reaction, namely, the oxidative rearrangement, PhI(OAc) in methanol is used as a non-natural reagent, whereas the enzymatic step requires only stoichiometric amounts of d-glucose along with catalytic amounts of IRED, glucose dehydrogenase (GDH), and the cofactor NADPH. This methodology, demonstrating the compatibility of a "classic" organic synthesis using a non-natural, highly reactive reagent and a subsequent biocatalytic step, can be applied for different amines as substrates, thus making this concept a versatile tool in synthetic organic chemistry in general and for enantioselective synthesis of heterocyclic secondary amines in particular.
本论文描述了化学酶一锅法的发展，该方法结合了氧化重排反应和由亚胺还原酶（IRED）催化的生物转化反应，用于合成对映体高度富集的仲胺，如芳基取代的吡咯烷和苯并氮杂卓。这种化学酶一锅法的优点包括高总转化率（高达>99%）、高对映体过量值（高达>99%），以及一种直接合成仲胺的方法，无需分离生成的中间体。对于初始化学反应，即氧化重排反应，甲醇中的PhI(OAc)被用作非天然试剂，而酶促步骤仅需要化学计量的d-葡萄糖以及催化量的IRED、葡萄糖脱氢酶（GDH）和辅因子NADPH。该方法证明了使用非天然的高反应性试剂进行“经典”有机合成与后续生物催化步骤的兼容性，可将不同的胺用作底物，因此，这一概念总体上是合成有机化学中的一种通用工具，尤其适用于对映选择性合成杂环仲胺。
