Asymmetric synthesis of 3-substituted cyclohexylamine derivatives from prochiral diketones via three biocatalytic steps

Siirola, E.; Mutti, F.G.; Grischek, B.; Hoefler, S.F.; Fabian, W.M.F.; Grogan, G.; Kroutil, W.;

Adv. Synth. Catal., 2013, 355, 1703-1708. DOI: 10.1002/adsc.201201057

2013_AdvSynCatal

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.

 
 
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