(R)-selective amination
View Patent ↗The present invention relates to a method for the enzymatic synthesis of enantiomerically enriched (R)-amines of general formula [1][c] from the corresponding ketones of the general formula [1][a] by using novel transaminases. These novel transaminases are selected from two different groups: either from a group of some 20 proteins with sequences as specified herein, or from a group of proteins having transaminase activity and isolated from a microorganism selected from the group of organisms consisting of Rahnella aquatilis, Ochrobactrum anthropi, Ochrobactrum tritici, Sinorhizobium morelense, Curtobacterium pusiffium, Paecilomyces lilacinus, Microbacterium ginsengisoli, Microbacterium trichothecenolyticum, Pseudomonas citronellolis, Yersinia kristensenii, Achromobacter spanius, Achromobacter insolitus, Mycobacterium fortuitum, Mycobacterium frederiksbergense, Mycobacterium sacrum, Mycobacterium fluoranthenivorans, Burkhoideria sp., Burkhoideria tropica, Cosmospora episphaeria , and Fusarium oxysporum.
1. A process for the enzymatic synthesis of an enantiomerically enriched (R)-amine of general formula [1][c]
from the corresponding ketone of the general formula [1][a]
and a suitable amino donor, wherein R 1 and R 2 are different and are independently linear or branched aliphatic, aromatic, hetero-aromatic or form a cyclic structure, by using a transaminase selected from the group consisting of a protein having at least 90% identity to the amino acid sequence of SEQ ID No. 1, wherein the transaminase has a transaminase enantioselectivity value (TEV) of at least approximately 5.
2. A process according to claim 1 , wherein R 1 and R 2 are different and R 1 and R 2 independently contain 1 to 30 carbon atoms and R 1 and R 2 are independently substituted or unsubstituted aliphatic; substituted or unsubstituted branched aliphatic; substituted or unsubstituted cyclic aliphatic; substituted or unsubstituted heterocyclic aliphatic, containing at least one oxygen, sulfur or nitrogen atom; substituted or unsubstituted aromatic; substituted or unsubstituted hetero-aromatic containing at least one sulfur or nitrogen atom; or together form a substituted or unsubstituted cyclic structure or heterocyclic structure, containing at least one oxygen, sulfur or nitrogen atom; wherein the substituents are selected from but not limited to the group consisting of a halogen atom, an alkyl group having 1 to 6 carbon atoms, hydroxyl group, methoxy group, monofluoromethyl, difluoromethyl and trifluoromethyl group.
3. A process according to claim 1 , wherein the final concentration of the enantiomerically enriched (R)-amine product lies between 1 and 50 weight % of the reaction mixture.
4. A process according to claim 1 , wherein the amino donor is α-methylbenzylamine.
5. A process according to claim 1 , wherein the amino donor is sec-butylamine.
6. A process according to claim 1 , wherein the final concentration of the enantiomerically enriched (R)-amine product lies between 5 and 35 weight % of the reaction mixture.
7. A process according to claim 1 , wherein the reaction mixture comprises an aqueous phase and second organic phase.
8. A process according to claim 1 , wherein the reaction mixture comprises an aqueous phase and second organic phase and the volumetric ratio of water:organic phase is between 100 and 0.01.
9. A process according to claim 1 , wherein the reaction mixture comprises an aqueous phase and second organic phase and the volumetric ratio of water:organic phase is between 20 and 0.1.
10. A process according to claim 1 , wherein the reaction mixture comprises an aqueous phase and second organic phase and the volumetric ratio of water:organic phase is between 20 and 1.
11. A process according to claim 1 , wherein the TEV is at least approximately 10.
12. A process according to claim 1 , wherein the TEV is at least approximately 15.