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US 6,281,379 B1Granted
Process for producing norstatin derivatives
AssigneeKaneka Corporation
InventorsAkio Fujii, Masanobu Sugawara, Kenji Inoue
Life of this patent
Estimating the term…
Abstract
This invention to provide a process for producing an optically active threo-phenylnorstatin derivative which does not require a toxic cyanating agent or a costly reagent, or a complicated procedure, and can be practiced on a commercial scale. This invention is directed to a process for producing a β-amino-α-hydroxy acid derivative which comprises treating either a γ-amino-β-keto sulfoxide derivative with a halogenating agent to produce a γ-amino-α-halo-β-keto sulfoxide derivative, treating the same with an acid and an alcohol to produce a β-amino-α-keto ester derivative or β-amino-α-keto acid derivative, and followed by reducing.
Claims38
A process for producing a β-amino-α-hydroxy acid derivative
- which comprises treating a γ-amino-β-keto sulfoxide derivative of the formula (1);
- wherein R1 represents a substituted or unsubstituted alkyl group of 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 30 carbon atoms or a substituted or unsubstituted aryl group of 6 to 30 carbon atoms;
- R2 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms or a substituted or unsubstituted aryl group of 6 to 20 carbon atoms;
- P1 and P2 may be the same or different and each represents a substituted or unsubstituted benzyl group, with a halogenating agent to produce a γ-amino-α-halo-β-keto sulfoxide derivative of the formula (2);
- wherein R1, R2, P1 and P2 are respectively as defined above;
- X represents a halogen atom,
- treating the derivative (2) with an acid and an alcohol of the formula (3);
- R3OH (3)
- wherein R3 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms,
- to produce a β-amino-α-keto ester derivative or β-amino-α-keto acid derivative of the formula (4);
- wherein R1, P1 and P2 are respectively as defined above;
- R4 represents a hydrogen atom, or a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms which corresponds to R3 in the above formula (3),
- and reducing the same derivative (4), optionally followed by cleaving the ester and/or deprotecting the amino group to give a β-amino-α-hydroxy acid derivative of the formula (5);
- wherein R1 and R4 are respectively as defined above;
- Q1 represents a hydrogen atom, or a substituted or unsubstituted benzyl group corresponding to P1 in the above formula (1);
- Q2 represents a hydrogen atom, or a substituted or unsubstituted benzyl group corresponding to P2 in the above formula (1).
13 more elements
A process for producing a β-amino-α-hydroxy acid derivative
- which comprises treating a γ-amino-β-keto sulfoxide derivative metal salt of the formula (6);
- wherein R1 represents a substituted or unsubstituted alkyl group of 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 30 carbon atoms or a substituted or unsubstituted aryl group of 6 to 30 carbon atoms;
- R2 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms or a substituted or unsubstituted aryl group of 6 to 20 carbon atoms;
- P1 and P2 may be the same or different and each represents a substituted or unsubstituted benzyl group;
- M represents an alkali metal or an alkaline earth metal halide, with a halogenating agent to produce a γ-amino-α-halo-β-keto sulfoxide derivative of the formula (2);
- wherein R1, R2, P1 and P2 are respectively as defined above;
- X represents a halogen atom,
- treating the derivative (2) with an acid and an alcohol of the formula (3);
- R3OH (3)
- wherein R3 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms,
- to produce a β-amino-α-keto ester derivative or β-amino-α-keto acid derivative of the formula (4);
- wherein R1, P1 and P2 are respectively as defined above;
- R4 represents a hydrogen atom, or a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms which corresponds to R3 in the above formula (3),
- and reducing the same derivative (4), optionally followed by cleaving the ester and/or deprotecting the amino group to give a β-amino-α-hydroxy acid derivative of the formula (5);
- wherein R1 and R4are respectively as defined above;
- Q1 represents a hydrogen atom, or a substituted or unsubstituted benzyl group corresponding to P1 in the above formula (1);
- Q2 represents a hydrogen atom, or a substituted or unsubstituted benzyl group corresponding to P2 in the above formula (1).
14 more elements
A process for producing a β-amino-α-keto ester derivative or β-amino-α-keto acid derivative
- which comprises treating a γ-amino-β-keto sulfoxide derivative of the formula (1);
- wherein R1 represents a substituted or unsubstituted alkyl group of 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 30 carbon atoms or a substituted or unsubstituted aryl group of 6 to 30 carbon atoms;
- R2 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms or a substituted or unsubstituted aryl group of 6 to 20 carbon atoms;
- P1 and P2 may be the same or different and each represents a substituted or unsubstituted benzyl group, with a halogenating agent to produce a γ-amino-α-halo-β-keto sulfoxide derivative of the formula (2);
- wherein R1, R2, P1 and P2 are respectively as defined above;
- X represents a halogen atom,
- treating the derivative (2) with an acid and an alcohol of the formula (3);
- R3OH (3)
- wherein R3 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms,
- to produce a β-amino-α-keto ester derivative or β-amino-α-keto acid derivative of the formula (4);
- wherein R1, P1 and P2 are respectively as defined above;
- R4 represents a hydrogen atom, or a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms which corresponds to R3 in the above formula (3).
9 more elements
A process for producing a β-amino-α-keto ester derivative or β-amino-α-keto acid derivative
- which comprises treating a γ-amino-β-keto sulfoxide derivative metal salt of the formula (6);
- wherein R1 represents a substituted or unsubstituted alkyl group of 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 30 carbon atoms or a substituted or unsubstituted aryl group of 6 to 30 carbon atoms;
- R2 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms or a substituted or unsubstituted aryl group of 6 to 20 carbon atoms;
- P1 and P2 may be the same or different and each represents a substituted or unsubstituted benzyl group;
- M represents an alkali metal or an alkaline earth metal halide, with a halogenating agent to produce a γ-amino-α-halo-β-keto sulfoxide derivative of the formula (2);
- wherein R1, R2, P1 and P2 are respectively as defined above;
- X represents a halogen atom,
- and treating the derivative (2) with an acid and an alcohol of the formula (3);
- R3OH (3)
- wherein R3 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms,
- to produce a β-amino-α-keto ester derivative or β-amino-α-keto acid derivative of the formula (4);
- wherein R1, P1 and P2 are respectively as defined above;
- R4 represents a hydrogen atom, or a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms or substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms which corresponds to R3 in the above formula (3).
10 more elements
A process for producing a γ-amino-α-halo-β-keto sulfoxide derivative
- which comprises treating a γ-amino-β-keto sulfoxide derivative of the formula (1);
- wherein R1 represents a substituted or unsubstituted alkyl group of 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 30 carbon atoms or a substituted or unsubstituted aryl group of 6 to 30 carbon atoms;
- R2 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms or a substituted or unsubstituted aryl group of 6 to 20 carbon atoms;
- P1 and P2 may be the same or different and each represents a substituted or unsubstituted benzyl group, with a halogenating agent to give a γ-amino-α-halo-β-keto sulfoxide derivative of the formula (2);
- wherein R1, R2, P1 and P2 are respectively as defined above;
- X represents a halogen atom.
3 more elements
A process for producing a γ-amino-α-halo-β-keto sulfoxide derivative
- which comprises treating a γ-amino-β-keto sulfoxide derivative metal salt of the formula (6);
- wherein R1 represents a substituted or unsubstituted alkyl group of 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 30 carbon atoms or a substituted or unsubstituted aryl group of 6 to 30 carbon atoms;
- R2 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms or a substituted or unsubstituted aryl group of 6 to 20 carbon atoms;
- P1 and P2 may be the same or different and each represents a substituted or unsubstituted benzyl group;
- M represents an alkali metal or an alkaline earth metal halide, with a halogenating agent to produce a γ-amino-α-halo-β-keto sulfoxide derivative of the formula (2);
- wherein R1, R2, P1 and P2 are respectively as defined above;
- X represents a halogen atom.
4 more elements
A compound of the formula (2);
- wherein R1 represents a substituted or unsubstituted alkyl group of 1 to 20 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 30 carbon atoms or a substituted or unsubstituted aryl group of 6 to 30 carbon atoms;
- R2 represents a substituted or unsubstituted alkyl group of 1 to 10 carbon atoms, a substituted or unsubstituted aralkyl group of 7 to 20 carbon atoms or a substituted or unsubstituted aryl group of 6 to 20 carbon atoms;
- P1 and P2 may be the same or different and each represents a substituted or unsubstituted benzyl group;
- X represents a halogen atom.
1 more element
Dependencies are inferred from the claim text.