SYNTHESIS OF

AMINO ACIDS
and PEPTIDE
BONDS
Done by:
Amaris Benjamin
Antonia Peters
Daniella Dhanesar
Darendra Guinness
Michaela Thomas
 21.6 Synthesis of Amino Acids.
HVZ Reaction Followed by Reaction with Ammonia
Hvz reaction replaces the C-H bond on the alpha-carbon of a carboxylic acid with a C-
Br bond.
The four stages are:
1. Conversion of the carboxylic acid to the acyl bromide
2. Tautomerization of the acyl bromide to its enol form (breaking C-H)
3. Bromination of the alpha-carbon of the enol (forming C-Br)
4. Hydrolysis of the acid bromide to the carboxylic acid.
Reducti ve Aminati on
 N-Phthalimidomalonic Ester Synthesis

These processes are built out of five reactions in total:

1. deprotonation of the ester to form an enolate
2. S N 2 of the enolate upon an alkyl halide, forming a new C-C bond
3. acidic hydrolysis of the ester to give a carboxylic acid
4. decarboxylation of the carboxylic acid to give an enol
5. tautomerization of the resulting enol to a carboxylic acid
4. Strecker Synthesis
a. The addition of cyanide ion to an imine, forming an alpha-amino nitrile. 
b. Hydrolyzed (e.g. with strong acid) to give an alpha-amino acid
STEPS IN THE N-PHTHALIMIDOMALONIC
ESTER SYNTHESIS
 A variation of the N-phthalimidomalonic ester
synthesis uses acetamidomalonic ester in place of N-
phthalimidomalonic ester.

Strecker Synthesis
 21.7 Resolution of Racemic Mixtures of
Amino Acids
Only the L-enantiomer is formed when amino
acids are synthesized in nature.
However, when amino acids are synthesized in
the laboratory, the product is a racemic
mixture of D and L amino acids. If only one
isomer is desired, the enantiomers must be
separated, which can be accomplished by
means of an enzyme-catalysed reaction.
Because an enzyme is chiral, it will react at a different
rate with each of the Enantiomers.
If the racemic mixture of amino acids is converted to a
pair of N –acetylamino acids and the
N -acetylated mixture is hydrolysed with pig kidney
aminoacylase, then the products will be
the l -amino acid and N -acetyl- d -amino acid, which
are easily separated.
The resolution of the enantiomers depends on the
difference in the rates of reaction of the
enzyme with the two N -acetylated compounds. This
technique is known as a kinetic
resolution.
Kinetic resolution is a means of differentiating two
enantiomers in a racemic mixture. In
kinetic resolution, two enantiomers react with different
reaction rates in a chemical reaction
with a chiral catalyst or reagent, resulting in an enantio
enriched sample of the less reactive
enantiomer. As opposed to chiral resolution, kinetic
resolution does not rely on different
physical properties of diastereomeric products, but rather on
the different chemical properties
of the racemic starting materials. This enantiomeric excess of
the unreacted starting material
continually rises as more product is formed, reaching 100%
just before full completion of the
reaction.
 21.8 PEPTIDE BONDS AND DISULFIDE
BONDS
A) What is a peptide bond?
A peptide bond is the amide bonds that links amino
acids. By convention, peptides and proteins are
written with the free amino group on the left and
the free carboxyl group on the right
How do you name a peptides?
When naming a peptide, adjective names (ending in
“yl”) are used for all the amino acids except the C-
terminal amino acid. Thus, the preceding
pentapeptide is
valylcysteinylalanylglutamylhistidine. Each amino
acid has the l configuration unless otherwise
specified
Characteristics of peptide bonds
A peptide bond has about 40% double-bond character because
of electron delocalization. Steric strain causes the
configuration that has the a-carbons of adjacent amino acids
on opposite side of the double bond to be more stable

The partial double-bond character prevents free rotation about the peptide
bond, so the carbon and nitrogen atoms of the peptide bond and the two
atoms to which each is attached are held rigidly in a plane .
B) Disulfide Bonds
Disulfide-
• A compound made up of two sulfur atoms (divalent
group SS) and an element or radical. (S-S bond)

• Under mild conditions, can be created from oxidized

thiols
Mechanism of Oxidization of Thiols to Disulfide
• A redox reaction.

• B2 or I2 is usually used as the oxidizing agent.

Mechanism of Oxidization of Thiols to Disulfide
Amino Acid Cysteine
• Cysteine is a distinct amino acid due to its side chain
comprising of two free thiol group that can generate
a cystine with a disulfide bridge bond.
Disulfide Bridge
• Between two cysteines, a disulfide bridge forms
from a tight covalent bond. The strength of disulfide
bridges aids protein stability and structure. Disulfide
bridges are particularly prevalent in proteins
secreted by cells.
Insulin
• It has one intrachain disulfide bridge and two
interchain disulfide bridges.

• The A-chain has 21 amino acids while the B-chain

has 30 amino acids.
Structure of Insulin
 SOME INTERESTING PEPTIDES
Several peptide hormones are synthesized by the body to control pain. B-
Endorphin has a chain of 31 amino acids, whereas leucine enkephalin and
methionine enkephalin are pentapeptides. The five amino acids at the N-
terminal end of b-endorphin are the same as those in methionine
enkephalin
These peptides control the body’s sensitivity to pain by binding to
receptors in certain brain cells. Part of their three-dimensional structures
must be similar to that of morphine because they bind to the same
receptors. The phenomenon known as “runner’s high” that kicks in after
vigorous exercise and the relief of pain through acupuncture are thought
to be due to the release of thesepeptides.
 The nonapeptides bradykinin, vasopressin, and oxytocin are also
peptide hormones. Bradykinin inhibits the inflammation of tissues.
Vasopressin controls blood pressure by regulating the contraction of
Smooth muscle; it is also an antidiuretic. Oxytocin induces labor in
pregnant women by stimulating the uterine muscle to contract; it
also stimulates milk production in nursing mothers. Vasopressin and
oxytocin, like b-endorphin and the enkephalins, also act on the
brain. Vasopressin is a “fight-or-flight” hormone, whereas
oxytocin has the opposite effect: it calms the body and promotes
social bonding. In spite of their very different physiological effects,
vasopressin and oxytocin differ only by two amino acids.
Vasopressin and oxytocin both have an intrachain disulfide bridge,
and their C-terminal amino acids contain amide rather than carboxyl
groups. Notice that the C-terminal amide group is indicated by
writing “NH2” after the name of the C-terminal amino acid.
The synthetic sweetener aspartame is about 200 times sweeter than
sucrose. Aspartame is the methyl ester of a dipeptide of l-aspartate
and
l-phenylalanine. The ethyl ester of the same dipeptide is not sweet.
If a d-amino acid is substituted for either of the l-amino acids of
aspartame, the resulting dipeptide is bitter rather than sweet.
Because aspartame contains phenylalanine, it cannot be used by
people with the genetic disease known as PKU
Conclusion
Amaris Benjamin- 21.8(B)
Antonia Peters-21.7
Daniella Dhanesar-21.8(A), Powerpoint
Darendra Guinness-21.7
Michaela Thomas-21.6,Conclusion
Monique Mcleish-21.9
 Reference
• Bruice, P. Y. Organic Chemistry, 8th ed.;
Pearson: Upper Saddle River, NJ, 2016.