Premium
Asymmetric Synthesis of 3‐Substituted Cyclohexylamine Derivatives from Prochiral Diketones via Three Biocatalytic Steps
Author(s) -
Siirola Elina,
Mutti Francesco G.,
Grischek Barbara,
Hoefler Sebastian F.,
Fabian Walter M. F.,
Grogan Gideon,
Kroutil Wolfgang
Publication year - 2013
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201201057
Subject(s) - cyclohexylamine , chemistry , diastereomer , substrate (aquarium) , organic chemistry , amination , hydrolysis , biocatalysis , enantioselective synthesis , lipase , solvent , solvolysis , stereochemistry , catalysis , reaction mechanism , enzyme , oceanography , geology
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 CC 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 CC 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.