Chemistry of biomolecules

Lecturer 4
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2- Amino acids and
proteins

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 Introduction
-Proteins are made up of α-amino acids units, linked together by
peptide linkage.
-They give on hydrolysis a mixture of α-amino acids.
-The amino acid molecules containing both amino and carboxyl
groups attached to the same α-carbon
-Proteins are composed of 20 different amino acid
-Their chemical structure influences three dimensional structure
of proteins.
-They are important intermediates in metabolism
-They can have hormonal and catalytic function.
-Several genetic disorders are cause in amino acid metabolism
errors
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 Essential Amino Acids in Humans

 Required in diet
 Humans incapable of forming requisite
carbon skeleton

Arginine* Lysine
Histidine* Methionine
Isoleucine Threonine
Leucine Phenylalanine
Valine Tryptophan
* Essential in children, not in adults
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 Non-Essential Amino Acids in Humans

 Not required in diet

 Can be formed from α-keto acids by transamination and
subsequent reactions

Alanine Glycine
Asparagine Proline
Aspartate Serine
Glutamate Cysteine (from Methionine *)
Glutamine Tyrosine (from Phenylalanine *)
* Essential amino acids
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 Classification of amino acids
I- Monoamino monocarboxylic acids

H H3 C H
H2C COOH H3C C COOH CH C COOH
NH2 NH2 H3C NH2
glycine alanine valine

H3C H2 H H3C CH2 H2 H2 H2 H

CH C C COOH H H3C C C C C C COOH
CH C COOH H2
H3C NH2 NH2
H3C NH2
leucine norleucine
isoleucine
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 II- Diamino monocarboxylic acids
NH H2 H2
H2 H2 H
H H2N C N C C C C COOH
H2C C C C C COOH H H2
H2 NH2
NH2 NH2
lysine arginine

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III- Monoamino dicarboxylic acids

H2C COOH
CH2 COOH
H2 C
HC COOH
CH COOH
NH2
NH2
aspartic acid glutamic acid

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 IV- Hydroxy amino monocarboxylic acids

H H H
H2C C COOH H3C C C COOH
OH NH2
OH NH2

serine threonine

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V- Hydroxy amino dicarboxylic acids

H2 C COOH
HO CH

CH COOH
NH2
hydroxy glutamic acid
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 VI- Aromatic amino acids

H2 H
C C COOH
NH2
phenylalanine
I
H2 H
H2 H HO C C COOH
HO C C COOH NH2
NH2 I

tyrosine iodogorgic acid

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VII- Heterocyclic amino acids
H2 N
C HC COOH
H
C C COOH
N H2
N H
NH2 NH2
H
tryptophan histidine

N COOH
H

proline 12
 VIII- Sulfur-containing amino acids

H2 H H H2 H2 H
HS C C COOH HOOC C C S S C C COOH
NH2 NH2 NH2
cysteine cystine

H2 H2 H2 H2 H
H H H3C S C C C COOH
HOOC C C S C C COOH
NH2 NH2
NH2
lanthioene methionine

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 Synthesis of amino acids
1- By reaction of α-halo acids with excess conc.
aqueous ammonia
Cl COOH + NH3 H2C COOH
C
H2 NH2
-chloro acetic acid glycine

H
H + NH3 H3C C COOH
H3C C COOH
NH2
Cl
-chloro propanoic acid alanine
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 2- Gabriel’s synthesis

O O O
O
NH3 alk. KOH
OH - H2O NH NK
O
OH
O O
O O N-potassim phthalimide
phthalimide
phthalic acid
O O
H H
NK + Cl C COOH N C COOH
CH3 -KCl
CH3
O 2-chloropropanoic acid O

O hydrolysis
H
OH + H2N C COOH
OH CH3
O alanine

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Modified Gabriel’s synthesis
COOEt COOEt
Br2
H2C Br HC
COOEt COOEt
malonic ester bromo malonic ester
O O
COOEt COOEt
-KBr
NK + Br HC N HC
COOEt COOEt
O O
N-potassim phthalimide NaOEt

O COOEt H2 O
COOEt
H2 Cl C COOEt
N C C COOEt N C
COOEt
O COOEt O

hydrolysis

O COOH COOH
OH H2 H2
+ H2N C C COOH H 2N C C COOH
OH -CO2 H
O COOH 16
aspartic acid
By the same method, synthesis of
methionine
COOEt COOEt
Br2
H 2C Br HC
COOEt COOEt
malonic ester bromo malonic ester
O O
COOEt COOEt
-KBr
NK + Br HC N HC
COOEt COOEt
O O
N-potassim phthalimide NaOEt

O COOEt O
COOEt
CH3SCH2CH2Cl
N C CH2CH2SCH3 N C
2-methylthio COOEt
O COOEt ethyl chloride O

hydrolysis

O COOH COOH
OH + heat
OH H2N C CH2CH2SCH3 -CO H 2N C CH2CH2SCH3
2 H
O COOH 17
methionine
Methionine Other name(s):a-amino-g-methylthiol-n-butyric acid
The Structure of Methionine. The chemical formula of methionine is
C5H11NO2S. In general, all amino acids have the same structure: an amino
group attached to a hydrogen, a carboxyl group and a side chain group,
denoted by 'R' via a central carbon. ... It is the side chain that is specific to
each different amino acid.
Overview Methionine is an essential amino acid. You need to get it through
your diet. It's needed to make protein and other compounds in your body.
Methionine is an antioxidant. It may help protect the body from damage
caused by ionizing radiation.

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 3- Using malonic ester

COOEt COOEt reduction COOEt

HNO2
H2C HON C H2N HC
COOEt COOEt COOEt
malonic ester
PhCOCl

COOEt
COOEt NaOEt
ClCH2CH2COOEt
PhCOHN HC
PhCOHN C
ethyl 3-chloropropanoate COOEt
COOEt

hydrolysis heat
COOEt COOH COOH
H2N C CH2CH2COOH -CO2
PhCOHN C CH2CH2COOEt H2N C CH2CH2COOH
H
COOEt COOH
glutamic acid

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 4- Strecker amino acid synthesis

 The Strecker amino acid synthesis, also known simply

as the Strecker synthesis, is a method for
the synthesis of amino acids by the reaction of an
aldehyde with ammonia in the presence of potassium
cyanide.

aminonitrile
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4- Strecker amino acid synthesis

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 5- Erlenmyer synthesis
 Hippuric acid, the benzamide derivative of glycine, cyclizes in the
presence of acetic anhydride, condensing to give 2-phenyl-oxazolone
. This intermediate also has two acidic protons and reacts with
benzaldehyde, acetic anhydride and sodium acetate to a so-called
azlactone. This compound on reduction gives access to phenylalanine.

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 5- Erlenmyer synthesis

Ph
NHCOPh NHCOPh
Ac2O N=C
C OH
HO CHO + H2C - H 2O HO C
HO C C
H COOH - H2O
COOH H COOH
hippuric acid

Ph
N=C NHCOPh NHCOPh
NaOH reduction H2
HO C C HO C C HO C HC
H O H
C COONa COONa

O
hydrolysis
azalactone

NH2
H2
HO C HC
COOH

tyrosine

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 Using 1H-indole-3-carbaldehyde instead of 4-hydroxy-
benzaldehyde gives tryptophan

CHO NHCOPh
H2 NH2
+ H2C C HC
COOH COOH
N N
H
H
1H-indole-3-carbaldehyde tryptophan

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CHO . NHCOPh NHCOPh
Ph
Ac2O H N=C
+ H2C C C H OH
- H 2O C C
N COOH COOH - H2O
N COOH
H hippuric acid N
H
H
Ph NHCOPh
H2
N=C NHCOPh C HC
NaOH H reduction
C C C C COONa
O N
H COONa
C
N N H
H O H
hydrolysis
azalactone
H2 NH2
C HC
COOH
N
H
tryptophan
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Chemistry of biomolecules

Lecturer 5
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