Patent ID: 6462221
Filing Date: 2002-10-08
Classification: C07B,C07C,Y02P

Abstract:
A method of preparing a 1-nitro-3-substituted-3-amino-2-propanol diastereomer represented by the following structural formula: wherein:R is an amine protecting group; and R1 is an amino acid side-chain, a protected amino acid side-chain, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted aralkyl or a substituted or unsubstituted heteroaralkyl group, comprising the steps of: a) contacting a 3S or 3R 1-nitro-3-substituted-3-amino-2-propanone with a carbonyl reducing agent to form a mixture of two 1-nitro-3-substituted-3-amino-2-propanol diastereomers; b) separating the 1-nitro-3-substituted-3-amino-2-propanol diastereomers by simulated moving bed chromatography to obtain: i) a first 1-nitro-3-substituted-3-amino-2-propanol diastereomer in at least 95% diastereomeric excess, and ii) a second 1-nitro-3-substituted-3-amino-2-propanol diastereomer or a mixture of the first 1-nitro-3-substituted-3-amino-2-propanol diastereomer and the second 1-nitro-3-substituted-3-amino-2-propanol diastereomer; c) contacting the second 1-nitro-3-substituted-3-amino-2-propanol diastereomer or a mixture of the second 1-nitro-3-substituted-3-amino-2-propanol diastereomer and the first 1-nitro-3-substituted-3-amino-2-propanol diastereomer with an oxidizing agent to reform a 1-nitro-3-substituted-3-amino-2-propanone; d) contacting the reformed 1-nitro-3-substituted-3-amino-2-propanone with a carbonyl reducing agent to form a second mixture of 1-nitro-3-substituted-3-amino-2-propanol diastereomers having a higher diastereomeric excess of the first 1-nitro-3-substituted-3-amino-2-propanol diastereomer than before oxidation; and e) separating the second mixture of 1-nitro-3-substituted-3-amino-2-propanol diastereomers by simulated moving bed chromatography to afford the first 1-nitro-3- substituted-3-amino-2-propanol diastereomer in 95% diastereomeric excess, and the second 1-nitro-3-substituted-3-amino-2-propanol diastereomer or a mixture of the first 1-nitro-3-substituted-3-amino-2-propanol diastereomer and the second 1-nitro-3-substituted-3-amino-2-propanol diastereomer is recovered.