Hydantoin → L-Isoleucine
Reaction equation
[NH:1]1[CH2:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].N[C@@H:9]([C:14](O)=O)[C@@H:10](CC)[CH3:11].N1CC(=O)NC1=[O:19].N[C@H](C(O)=[O:31])[C@@H](CC)C.N1CC(=O)NC1=[O:35].N[C@@H](C(O)=O)[C@@H](CC)C.C(N[C@@H](C(O)=O)[C@@H](CC)C)(=O)N.C(N[C@@H](C(O)=O)[C@H](CC)C)(=O)N.N[C@H](C(O)=O)[C@@H](CC)C>>[NH:1]1[CH2:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].[NH2:1][C@@H:7]([C:5]([OH:19])=[O:6])[C@@H:9]([CH2:10][CH3:11])[CH3:14].[NH:1]1[CH2:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].[NH2:1][C@H:7]([C:5]([OH:31])=[O:6])[C@@H:9]([CH2:10][CH3:11])[CH3:14].[NH2:1][C@H:7]([C:5]([OH:35])=[O:6])[C@H:9]([CH2:10][CH3:11])[CH3:14]Participants
Reactant 7
Product 3
Procedure
When this racemization occurs in the presence of a D-hydantoinase, an equilibrium is established between hydantoins possessing the R and S absolute configurations at C-5 of the hydantoin. For example, an equilibrium would be established between L-isoleucine hydantoin and D-allo-isoleucine hydantoin; similarly an equilibrium would be established between L-allo-isoleucine hydantoin and D-isoleucine hydantoin. When a mixture of L-isoleucine hydantoin and D-allo-isoleucine hydantoin is contacted with a D-hydantoinase, the D-allo-isoleucine hydantoin is selectively hydrolyzed by the D-hydantoinase to form the N-carbamoyl-D-allo-isoleucine. As the D-allo-isoleucine hydantoin is depleted from the mixture by D-hydantoinase-catalyzed hydrolysis, the equilibrium between the L-isoleucine hydantoin and the D-allo-isoleucine hydantoin is re-established under the epimerizing conditions, continuously generating additional D-allo-isoleucine hydantoin for stereoselective hydrolysis by the D-hydantoinase enzyme. This continual supply of the hydantoin of D-allo-isoleucine occurs during the course of the reaction until substantially all of the hydantoin has been converted to N-carbamoyl-D-allo-isoleucine. In this way, the reaction can be carried out to substantial completion. By the term “substantial completion” is meant that at least about 75%, preferably at least about 85%, and more preferably at least about 95%, of the mixture of L-isoleucine hydantoin and D-allo-isoleucine hydantoin is converted to N-carbamoyl-D-allo-isoleucine. The yield of N-carbamoyl-D-allo-isoleucine produced by the method of the present invention can approach 100% of theoretical, given sufficient reaction time and/or sufficient hydantoinase enzyme. Similarly, when a mixture of D-isoleucine hydantoin and L-allo-isoleucine hydantoin is contacted with a D-hydantoinase, the D-isoleucine hydantoin is selectively hydrolyzed by the D-hydantoinase to form the N-carbamoyl-D-isoleucine. As the D-isoleucine hydantoin is depleted from the mixture by D-hydantoinase-catalyzed hydrolysis, the equilibrium between the L-allo-isoleucine hydantoin and the D-isoleucine hydantoin is re-established under the epimerizing conditions, continuously generating additional D-isoleucine hydantoin for stereoselective hydrolysis by the D-hydantoinase enzyme. This continual supply of the hydantoin of D-isoleucine occurs during the course of the reaction until substantially all of the mixture of D-isoleucine hydantoin and L-allo-isoleucine hydantoin has been converted to N-carbamoyl-D-isoleucine. In this way, the reaction can be carried out to substantial completion so that the mixture of D-isoleucine hydantoin and L-allo-isoleucine hydantoin is converted almost completely to N-carbamoyl-D-allo-isoleucine. In similar fashion using an L-hydantoinase, L-allo-isoleucine can be produced from a mixture of D-isoleucine hydantoin and L-allo-isoleucine hydantoin, and L-isoleucine can be produced form a mixture of D-allo-isoleucine hydantoin and L-isoleucine hydantoin.
Workup
- customfor stereoselective hydrolysis by the D-hydantoinase enzyme
- customIn this way, the reaction
Sources & evidence
- ORD record
- ord-51fd6807d5ea40d48defb46740d5cf41
- Source dataset
- uspto-grants-2004_12
- Patent number
- US06830904B2
Reaction notes
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