The good understanding of the cyclohexane ring conformation and its easy amenability to Structure Activity Relationship has made this ring system an attractive scaffold for medicinal chemists for various applications. The 1-substituted-4-aminocyclohexanol framework especially has in the last few years been extensively used by research chemists.1 Unfortunately, to date there is no general synthesis affording this building block in high diastereomeric excess. Indeed, a cis/trans mixture is usually obtained, and the products have to be separed by chromatography or crystallyzation of the corresponding salts. In this work we employ a number of amino-transaminases (ATA) for carrying out a diastereoselective synthesis of such amines starting from the corresponding ketones, in alternative to the chemical reductive amination. The starting material was converted in good yields, d.e. are in general higher compared with the chemical synthesis, and in some cases are excellent. In some cases, varying the enzymes, the opposite diastereomers were obtained. Figure 1. Reaction scheme. [1] Gallou, F., Han, B., Lu, J., Seeger-Weibel, M., Stoessel, A. F., & Allmendinger, S. (2010). A rapid and practical entry into cis-1, 4-aminocyclohexanols.Tetrahedron Letters, 51(10), 1419-1422.

BIOCATALYTIC SYNTHESIS OF 4-SUBSTITUTED CYCLOHEXYLAMINES

D. Tessaro;P. D’Arrigo;L. Cerioli;A. Fiorati
2017

Abstract

The good understanding of the cyclohexane ring conformation and its easy amenability to Structure Activity Relationship has made this ring system an attractive scaffold for medicinal chemists for various applications. The 1-substituted-4-aminocyclohexanol framework especially has in the last few years been extensively used by research chemists.1 Unfortunately, to date there is no general synthesis affording this building block in high diastereomeric excess. Indeed, a cis/trans mixture is usually obtained, and the products have to be separed by chromatography or crystallyzation of the corresponding salts. In this work we employ a number of amino-transaminases (ATA) for carrying out a diastereoselective synthesis of such amines starting from the corresponding ketones, in alternative to the chemical reductive amination. The starting material was converted in good yields, d.e. are in general higher compared with the chemical synthesis, and in some cases are excellent. In some cases, varying the enzymes, the opposite diastereomers were obtained. Figure 1. Reaction scheme. [1] Gallou, F., Han, B., Lu, J., Seeger-Weibel, M., Stoessel, A. F., & Allmendinger, S. (2010). A rapid and practical entry into cis-1, 4-aminocyclohexanols.Tetrahedron Letters, 51(10), 1419-1422.
978-963-9970-76-2
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11311/1047110
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