Hydantoin → D-Isoleucine
Reaction equation
N1CC(=O)NC1=O.[NH2:8][C@@H:9]([C:14]([OH:16])=[O:15])[C@@H:10]([CH2:12][CH3:13])[CH3:11].N1CC(=O)NC1=O.N[C@H](C(O)=O)[C@@H](CC)C.N1CC(=O)NC1=O.C(N[C@@H](C(O)=O)[C@@H](CC)C)(=O)N>C[C@H](CC)C=O>[NH2:8][C@@H:9]([C:14]([OH:16])=[O:15])[C@@H:10]([CH2:12][CH3:13])[CH3:11]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
The invention is directed to methods for the preparation of any of the four diastereomers of the isoleucine carbon skeleton in high stereochemical purity. In one embodiment as shown in Scheme 1, the invention is directed to a method for producing D-isoleucine comprising converting (R)-2-methylbutyraldehyde to a diastereomeric mixture of D-isoleucine hydantoin (5R-[(R)-1-methylpropyl]hydantoin) and L-allo-isoleucine hydantoin (5S-[(R)-1-methylpropyl]hydantoin) under conditions whereby no significant racemization of the chiral center in (R)-2-methylbutyraldehyde occurs, followed by contacting said diastereomeric hydantoin mixture with a D-hydantoinase to stereoselectively hydrolyze any D-isoleucine hydantoin in the mixture to the corresponding N-carbamoyl-D-isoleucine. Preferably in the claimed method the contacting of the diastereomeric hydantoin mixture with a D-hydantoinase is carried out under conditions permitting the simultaneous epimerization of the chiral center at C-5 of the hydantoin. As discussed further below, the simultaneous epimerization permits the reaction to be carried out to substantial completion so that the diastereomeric hydantoin mixture is converted to N-carbamoyl-D-isoleucine in high yield. The N-carbamoyl-D-isoleucine is then decarbamoylated to produce D-isoleucine.
Workup
- customthe reaction
Sources & evidence
- ORD record
- ord-5b150737d7fb4b298725bedaf5ed4575
- Source dataset
- uspto-grants-2004_12
- Patent number
- US06830904B2
Reaction notes
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