Method for producing lysine derivative
AssigneeAjinomoto Co., Inc.
InventorsMasakazu Nakazawa, Daisuke Takahashi, Norimasa Onishi, Masaki Naito, Kunisuke Izawa, Kenzo Yokozeki
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Abstract
The present invention provides a method for industrially producing an optically active lysine derivative useful as a pharmaceutical intermediate. More particularly, the present invention provides a production method including protecting an amino group or an amino group and carboxyl group of optically active 2-amino-6-methyl-6-nitroheptanoic acid with a protecting group, reducing a nitro group to synthesize a 6,6-dimethyl lysine derivative and reacting the 6,6-dimethyl lysine derivative with an acetic acid derivative.
Claims20
A method for producing an optically active lysine derivative of the formula (5)
- wherein
- * means an asymmetric carbon atom,
- P1 and P2 are each independently an amino-protecting group or hydrogen atom where P1 and P2 are not hydrogen atoms at the same time, or P1 and P2 in combination show an amino-protecting group,
- R1 is alkyl group having 1 to 6 carbon atoms or aralkyl group having 7 to 12 carbon atoms, and
- P5 is a hydrogen atom or carboxyl-protecting group
- or a salt thereof, which method comprises the steps of
- (1) protecting an amino group or an amino group and a carboxyl group of optically active 2-amino-6-methyl-6-nitroheptanoic acid of the formula (1)
- wherein * is as defined above, or a salt thereof, with a protecting group to give an optically active amino acid derivative of the formula (2)
- wherein *, P1 and P2 are as defined above and P3 is a hydrogen atom or carboxyl-protecting group,
- (2) reducing a nitro group of the derivative of the formula (2) to give an optically active 6,6-dimethyl lysine derivative of the formula (3)
- wherein *, P1 and P2 are as defined above and P4 is a hydrogen atom or carboxyl-protecting group, or a salt thereof, and
- (3) reacting the derivative of the formula (3) or a salt thereof with an acetate derivative of the formula (4)
- wherein Y1 is a leaving group and R1 is as defined above.
A method for producing an optically active 6,6-dimethyl lysine derivative of the formula (3)
- wherein
- * means an asymmetric carbon atom,
- P1 and P2 are each independently an amino-protecting group or hydrogen atom where P1 and P2 are not hydrogen atoms at the same time, or P1 and P2 in combination show an amino-protecting group, and
- P4 is a hydrogen atom or carboxyl-protecting group,
- or a salt thereof, which method comprises protecting an amino group or an amino group and a carboxyl group of optically active 2-amino-6-methyl-6-nitroheptanoic acid of the formula (1)
- wherein * is as defined above, or a salt thereof, with a protecting group to give an optically active amino acid derivative of the formula (2)
- wherein *, P1 and P2 are as defined above and P3 is a hydrogen atom or carboxyl-protecting group, and reducing a nitro group of the derivative of the formula (2).
A method for producing an optically active 6,6-dimethyl lysine derivative of the formula (3)
- wherein
- * means an asymmetric carbon atom,
- P1 and P2 are each independently an amino-protecting group or hydrogen atom where P1 and P2 are not hydrogen atoms at the same time, or P1 and P2 in combination show an amino-protecting group, and
- P4 is a hydrogen atom or carboxyl-protecting group,
- or a salt thereof, which method comprises reducing an amino acid derivative of the formula (2)
- wherein *, P1 and P2 are as defined above and P3 is a hydrogen atom or carboxyl-protecting group.
A method for producing an optically active lysine derivative of the formula (5)
- wherein
- * means an asymmetric carbon atom,
- P1 and P2 are each independently an amino-protecting group or hydrogen atom where P1 and P2 are not hydrogen atoms at the same time, or P1 and P2 in combination show an amino-protecting group,
- R1 is alkyl group having 1 to 6 carbon atoms or aralkyl group having 7 to 12 carbon atoms, and
- P5 is a hydrogen atom or carboxyl-protecting group,
- or a salt thereof, which method comprises reacting an optically active 6,6-dimethyl lysine derivative of the formula (3)
- wherein *, P1 and P2 are as defined above and P4 is a hydrogen atom or carboxyl-protecting group, or a salt thereof, with an acetate derivative of the formula (4)
- wherein Y1 is a leaving group and R1 is as defined above.
Dependencies are inferred from the claim text.