Asymmetric Synthesis of 3-Substituted Cyclohexylamine Derivatives from Prochiral Diketones via Three Biocatalytic Steps

• Published in: Advanced synthesis & catalysis Vol. 355; no. 9; pp. 1703 - 1708
• Main Authors: Siirola, Elina, Mutti, Francesco G., Grischek, Barbara, Hoefler, Sebastian F., Fabian, Walter M. F., Grogan, Gideon, Kroutil, Wolfgang
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 17.06.2013; WILEY‐VCH Verlag; Wiley
• Subjects: asymmetric catalysis; Asymmetry; biosynthesis; biotransformations; Carbon-carbon composites; Cascades; Chemistry; Chemistry, Applied; Chemistry, Organic; CC hydrolase; Derivatives; Diketones; Esterification; Physical Sciences; Science & Technology; Solvents; Synthesis; ω-transaminases; BICYCLIC BETA-DIKETONES; biotransformations; CASCADE; asymmetric catalysis; omega-transaminases; CHIRAL AMINES; KETONES; AMINATION; ENZYME; PYRUVATE TRANSAMINASE; KINETIC RESOLUTION; biosynthesis; RETRO-CLAISEN REACTION; CC hydrolase
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201201057

Prochiral bicyclic diketones were transformed to a single diastereomer of 3‐substituted cyclohexylamine derivatives via three consecutive biocatalytic steps. The two chiral centres were set up by a CC hydrolase (6‐oxocamphor hydrolase) in the first step and by an ω‐transaminase in the last step. The esterification of the intermediate keto acid was catalysed by a lipase in the second step if possible. For two substrates the CC hydrolytic step as well as the esterification could be run simultaneously in a one‐pot cascade in an organic solvent. In one example, the reaction mixture of the first two steps could be directly subjected to bio‐amination in an organic solvent without the need to change the reaction medium. Depending on the choice of the ω‐transaminase employed and the substrate the cis‐ as well as the trans‐diastereomers could be obtained in optically pure forms.