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27.4
Synthesis of Amino Acids
From a-Halo Carboxylic Acids
O
CH3CHCOH + 2NH3
Br
H2O
O
–
CH3CHCO + NH4Br
+NH3
(65-70%)
Strecker Synthesis
O
CH3CH
NH4Cl
NaCN
CH3CHC
N
NH2
1. H2O, HCl, heat
2. HO–
O
–
CH3CHCO
+NH3
(52-60%)
Using Diethyl Acetamidomalonate
O
O
C
C
C
CH3CH2O
CH3CNH
H
OCH2CH3
O
Can be used in the same manner as diethyl
malonate (Section 21.7).
Example
O O
CH3CH2OCCCOCH2CH3
H
CH3CNH
O
1. NaOCH2CH3
2. C6H5CH2Cl
O O
CH3CH2OCCCOCH2CH3
CH3CNH
O
CH2C6H5
(90%)
O O
Example
HOCCCOH
CH2C6H5
H3 N
+
HBr, H2O, heat
O O
CH3CH2OCCCOCH2CH3
CH3CNH
O
CH2C6H5
O
Example
HCCOH
(65%)
CH2C6H5
H3 N
+
HBr, H2O, heat
O O
CH3CH2OCCCOCH2CH3
CH3CNH
O
CH2C6H5
27.5
Reactions of Amino Acids
Acylation of Amino Group
The amino nitrogen of an amino acid can be
converted to an amide with the customary
acylating agents.
O
O O
+
– +
H3NCH2CO
CH3COCCH3
O
O
CH3CNHCH2COH
(89-92%)
Esterification of Carboxyl Group
The carboxyl group of an amino acid can be
converted to an ester. The following illustrates
Fischer esterification of alanine.
O
+
– +
H3NCHCO
CH3CH2OH
CH3
HCl
O
Cl
–
+
H3NCHCOCH2CH3
CH3
(90-95%)
Ninhydrin Test
Amino acids are detected by the formation of a purple
color on treatment with ninhydrin.
O
O
OH
+
+ H3NCHCO–
OH
R
O
O
O–
O
RCH + CO2 + H2O +
N
O
O
27.6
Some Biochemical Reactions
of Amino Acids
Biosynthesis of L-Glutamic Acid
O
HO2CCH2CH2CCO2H + NH3
enzymes and
reducing coenzymes
–
HO2CCH2CH2CHCO2
+ NH3
This reaction is the biochemical analog of reductive
amination (Section 22.11).
Transamination via L-Glutamic Acid
O
–
HO2CCH2CH2CHCO2
+
CH3CCO2H
+ NH3
L-Glutamic acid acts as a source of the amine
group in the biochemical conversion of a-keto
acids to other amino acids. In the example
shown, pyruvic acid is converted to L-alanine.
Transamination via L-Glutamic Acid
O
–
HO2CCH2CH2CHCO2
+
CH3CCO2H
+ NH3
enzymes
O
HO2CCH2CH2CCO2H
–
+ CH3CHCO2
+ NH3
Mechanism
O
–
HO2CCH2CH2CHCO2
+
CH3CCO2H
+ NH3
The first step is imine formation between the
amino group of L-glutamic acid and pyruvic
acid.
Mechanism
O
–
HO2CCH2CH2CHCO2
+
CH3CCO2H
+ NH3
–
HO2CCH2CH2CHCO2
N
CH3CCO2–
Formation of the imine is followed by proton
removal at one carbon and protonation of
another carbon.
H
–
HO2CCH2CH2CCO2
N
CH3CCO2–
HO2CCH2CH2CCO2
N
–
CH3CCO2
H
H
–
HO2CCH2CH2CCO2
N
CH3CCO2–
–
HO2CCH2CH2CCO2
N
–
CH3CCO2
H
Hydrolysis of the imine function gives
a-keto glutarate and L-alanine.
–
HO2CCH2CH2CCO2
N
–
CH3CCO2
H
H2O
+NH3
–
HO2CCH2CH2CCO2
O
+
CH3CCO2–
H
Biosynthesis of L-Tyrosine
L-Tyrosine is biosynthesized from L-phenylalanine.
A key step is epoxidation of the aromatic ring to
give an arene oxide intermediate.
–
CH2CHCO2
+ NH3
Biosynthesis of L-Tyrosine
–
CH2CHCO2
O
+ NH3
O2, enzyme
–
CH2CHCO2
+ NH3
Biosynthesis of L-Tyrosine
–
CH2CHCO2
O
+ NH3
enzyme
HO
–
CH2CHCO2
+ NH3
Biosynthesis of L-Tyrosine
Conversion to L-tyrosine is one of the major
metabolic pathways of L-phenylalanine.
Individuals who lack the enzymes necessary to
convert L-phenylalanine to L-tyrosine can suffer
from PKU disease. In PKU disease, Lphenylalanine is diverted to a pathway leading
to phenylpyruvic acid, which is toxic.
Newborns are routinely tested for PKU disease.
Treatment consists of reducing their dietary
intake of phenylalanine-rich proteins.
Decarboxylation
Decarboxylation is a common reaction of aamino acids. An example is the conversion of
L-histidine to histamine. Antihistamines act by
blocking the action of histamine.
N
–
CH2CHCO2
N
H
+ NH3
Decarboxylation
N
CH2CH2 NH2
N
H
–CO2, enzymes
N
–
CH2CHCO2
N
H
+ NH3
Neurotransmitters
–
The chemistry of the
brain and central
nervous system is
affected by
neurotransmitters.
Several important
neurotransmitters
are biosynthesized
from L-tyrosine.
+
H3N
H
CO2
H
H
OH
L-Tyrosine
Neurotransmitters
–
The common name
of this compound is
L-DOPA. It occurs
naturally in the
brain. It is widely
prescribed to reduce
the symptoms of
Parkinsonism.
+
H3N
H
CO2
H
H
HO
OH
L-3,4-Dihydroxyphenylalanine
Neurotransmitters
Dopamine is formed
by decarboxylation
of L-DOPA.
H
H2N
H
H
H
HO
OH
Dopamine
Neurotransmitters
H
H2N
H
H
OH
HO
OH
Norepinephrine
Neurotransmitters
H
CH3NH
H
H
OH
HO
OH
Epinephrine