Method for producing n-alkyl amino acid and peptide including n-alkyl amino acid

A method for producing an N-monoalkylamino acid or an ester thereof or a peptide containing the N-monoalkylamino acid or an ester thereof, the method comprising:

• an alkylation step of mixing a starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof, a C1-C6 primary alkylating agent or a substituted methyl halide, a hydride reducing agent, and a catalyst in a solvent,
• wherein the alkylation step produces an N-monoalkylamino acid or an ester thereof or a peptide containing the N-monoalkylamino acid or an ester thereof in which a primary alkyl group corresponding to the C1-C6 primary alkylating agent or the substituted methyl halide is attached to an amino group of the starting amino acid or an ester thereof.

A method of suppressing a production of a dialkylated compound in an N-monoalkylation reaction of a starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof, wherein the dialkylated compound is a compound in which an amino group of the starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof is dialkylated, the method comprising:

• an alkylation step of mixing a starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof, a C1-C6 primary alkylating agent or a substituted methyl halide, and a catalyst in a solvent in the presence of hydrogen,
• wherein the alkylation step is carried out at a pressure of 1 atm or more, and produces an N-monoalkylamino acid or an ester thereof or a peptide containing the N-monoalkylamino acid or an ester thereof in which a primary alkyl group corresponding to the C1-C6 primary alkylating agent or the substituted methyl halide is attached to an amino group of the starting amino acid or an ester thereof.

A method of suppressing a production of a dialkylated compound in an N-monoalkylation reaction of a starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof, wherein the dialkylated compound is a compound in which an amino group of the starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof is dialkylated, the method comprising:

• an alkylation step of mixing a starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof, a C1-C6 primary alkylating agent or a substituted methyl halide, a hydride reducing agent, and a catalyst in a solvent,
• wherein the alkylation step produces an N-monoalkylamino acid or an ester thereof or a peptide containing the N-monoalkylamino acid or an ester thereof in which a primary alkyl group corresponding to the C1-C6 primary alkylating agent or the substituted methyl halide is attached to an amino group of the starting amino acid or an ester thereof.