Organic Chemistry

(Dana P.) #1
972 CHAPTER 23 Amino Acids, Peptides, and Proteins

23.6 Resolution of Racemic Mixtures of Amino Acids


Chemists do not have to rely on nature to produce amino acids; they can synthesize
them in the laboratory, using a variety of methods. One of the oldest methods replaces
an of a carboxylic acid with a bromine in a Hell–Volhard–Zelinski reac-
tion (Section 19.5). The resulting acid then undergoes an re-
action with ammonia to form the amino acid (Section 10.4).

PROBLEM 16

Why is excess ammonia used in the preceding reaction?

When amino acids are synthesized in nature, only the L-enantiomer is formed
(Section 5.20). However, when amino acids are synthesized in the laboratory, the
product is usually a racemic mixture of Dand Lenantiomers. If only one isomer is de-
sired, the enantiomers must be separated. They can be separated by means of an en-
zyme-catalyzed reaction. Because an enzyme is chiral, it will react at a different rate
with each of the enantiomers (Section 5.20). For example, pig kidney aminoacylase is
an enzyme that catalyzes the hydrolysis of N-acetyl-L-amino acids, but not N-acetyl-
D-amino acids. Therefore, if the racemic amino acid is converted into a pair of
N-acetylamino acids and the N-acetylated mixture is hydrolyzed with pig kidney
aminoacylase, the products will be the L-amino acid and N-acetyl-D-amino acid, which
are easily separated. Because the resolution (separation) of the enantiomers depends
on the difference in the rates of reaction of the enzyme with the two N-acetylated com-
pounds, this technique is known as a kinetic resolution.

PROBLEM 17

Pig liver esterase is an enzyme that catalyzes the hydrolysis of esters. It hydrolyzes esters
of L-amino acids more rapidly than esters of D-amino acids. How can this enzyme be used
to separate a racemic mixture of amino acids?

PROBLEM 18

Amino acids can be synthesized by reductive amination of acids (Section 21.8).

+NH
3

O

O

excess ammonia
RC C OH H 2 /Raney Ni

O

RCH C O−

a-keto

O

Br

a carboxylic
acid


  1. Br 2 , PBr 3
    RCH 2 COH 2. H 3 O+


O

RCHCOH

O

RCHCO− + NH 4 Br−

+

excess
NH 3

an amino acid

+NH
3

a-bromocarboxylic SN 2

a-hydrogen

O

D-amino acid
+
L-amino acid

CH 3 COCCH 3
H 2 NCHCO−

R

O O

N-acetyl-D-amino acid
+
N-acetyl-L-amino acid

CH 3 C NHCHCO−

O

CH 3 CO−

R

pig kidney
aminoacylase
H 2 O

OO

+ CH 3 C NHCHCO−

R

R

CO−
H 2 N H +

O
OO

L-amino acid

N-acetyl-D-amino acid

BRUI23-959-998r2 29-03-2003 1:36 PM Page 972

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