de Souza Rodrigo O M A, Miranda Leandro S M, Bornscheuer Uwe T
Biocatalysis and Organic Synthesis Group, Federal University of Rio de Janeiro, Chemistry Institute, 21941909, Rio de Janeiro, Brazil.
Dept. of Biotechnology & Enzyme Catalysis, Institute of Biochemistry, Greifswald University, Felix-Hausdorff-Str. 4, 17487, Greifswald, Germany.
Chemistry. 2017 Sep 7;23(50):12040-12063. doi: 10.1002/chem.201702235. Epub 2017 Jun 22.
For the planning of an organic synthesis route, the disconnection approach guided by retrosynthetic analysis of possible intermediates and the chemical reactions involved, back to ready available starting materials, is well established. In contrast, such concepts just get developed for biocatalytic routes. In this Review we highlight functional group interconversions catalyzed by enzymes. The article is organized rather by chemical bonds formed-exemplified for C-N, C-O- and C-C-bonds-and not by enzyme classes, covering a broad range of reactions to incorporate the desired functionality in the target molecule. Furthermore, the successful use of biocatalysts, also in combination with chemical steps, is exemplified for the synthesis of various drugs and advanced pharmaceutical intermediates such as Crispine A, Sitagliptin and Atorvastatin. This Review also provides some basic guidelines to choose the most appropriate enzyme for a targeted reaction keeping in mind aspects like commercial availability, cofactor-requirement, solvent tolerance, use of isolated enzymes or whole cell recombinant microorganisms aiming to assist organic chemists in the use of enzymes for synthetic applications.
对于有机合成路线的规划，通过对可能的中间体和所涉及的化学反应进行逆合成分析来指导切断方法，追溯到容易获得的起始原料，这一方法已得到广泛确立。相比之下，此类概念才刚刚开始应用于生物催化路线。在本综述中，我们重点介绍了酶催化的官能团相互转化。本文的组织方式是按照形成的化学键——以C-N、C-O和C-C键为例——而不是按照酶的类别，涵盖了广泛的反应，以便在目标分子中引入所需的官能团。此外，还举例说明了生物催化剂在合成各种药物和高级药物中间体（如Crispine A、西他列汀和阿托伐他汀）中的成功应用，包括与化学步骤相结合的情况。本综述还提供了一些基本指导方针，以便在考虑商业可得性、辅因子需求、溶剂耐受性、使用分离的酶或全细胞重组微生物等方面的情况下，为特定反应选择最合适的酶，旨在帮助有机化学家将酶用于合成应用。
