One‐pot Synthesis of 4‐Aminocyclohexanol Isomers by Combining a Keto Reductase and an Amine Transaminase. Issue 23 (21st August 2019)

• Record Type: Journal Article
• Authors: Sviatenko, Olha; Ríos‐Lombardía, Nicolás; Morís, Francisco; González‐Sabín, Javier; Venkata Manideep, Kollipara; Merdivan, Simon; Günther, Sebastian; Süss, Philipp; Höhne, Matthias
• Is Part Of: ChemCatChem. Volume 11:Issue 23(2019)
• Page Start: 5794
• Page End: 5799
• Publication Date: 2019-08-21
• Subjects: amino alcohols -- asymmetric catalysis -- enzyme catalysis -- amine transaminase -- ketoreductase; Catalysis -- Periodicals; 541.39505
• DOI: 10.1002/cctc.201900733
• Languages: English
• ISSNs: 1867-3880

Abstract

Abstract: The efficient multifunctionalization by one‐pot or cascade catalytic systems has developed as an important research field, but is often challenging due to incompatibilities or cross‐reactivities of the catalysts leading to side product formation. Herein we report the stereoselective preparation of cis ‐ and trans ‐4‐aminocyclohexanol from the potentially bio‐based precursor 1, 4‐cyclohexanedione. We identified regio‐ and stereoselective enzymes catalyzing reduction and transamination of the diketone, which can be performed in a one‐pot sequential or cascade mode. For this, we identified regioselective keto reductases for the selective mono reduction of the diketone to give 4‐hydroxycyclohexanone. The system is modular and by choosing stereocomplementary amine transaminases, both cis ‐ and trans ‐4‐aminocyclohexanol were synthesized with good to excellent diastereomeric ratios. Furthermore, we identified an amine transaminase that produces cis ‐1, 4‐cyclohexanediamine with diastereomeric ratios >98 : 2. These examples highlight that the high selectivity of enzymes enable short and stereoselective cascade multifunctionalizations to generate high‐value building blocks from renewable starting materials. Introduction Abstract : Avoiding cross‐reactivity : Identifying selective keto reductases and amine transaminases facilitated the synthesis of 4‐aminocyclohexanol isomers. The starting diketone can be prepared from renewable resources, and its enzymatic functionalization is possible in a one‐pot or concurrent cascade approach. The 4‐aminocyclohexanol isomers are valuable motifs for the synthesis of pharmaceuticals for the treatment of cardiovascular, respiratory, viral diseases, diabetes and obesity.