8.

BIOLOGICAL MOLECULES
• The major classes of organic compounds common to living systems are
carbohydrates, amino acids, proteins, lipids, and nucleic acids.
• They are also known as primary metabolites
8.1 Introduction to carbohydrate chemistry
Carbohydrates or saccharides (Greek: sakcharon, Latin: saccharum, sugar)
• Early chemists noted that carbohydrates have molecular formulas
Cn(H2O)n, where n  3 & that make them appear to be hydrates of carbon
• Later structural studies revealed that they were not hydrates b/c they did
not contain intact water molecules, but the term “carbohydrate” persists).
• They are usually defined as polyhydroxy aldehydes and ketones or
substances that hydrolyze to yield polyhydroxy aldehydes and ketones
• The most abundant biomolecules on earth
• They provide energy through oxidation
• They supply carbon for the synthesis of cell components
• They serve as a form of stored chemical energy
• They form part of the structures of some cells and tissues
 Classification of Carbohydrates
• According to the number of sugar units and the size of the molecule,
there are two major classes of carbohydrates:
I. Simple carbohydrates are monosaccharides (single sugars)
Consist of a single polyhydroxy aldehyde or ketone unit
II. Complex carbohydrates - two or more sugar sub-units linked together.
A. Disaccharides - two monosaccharides covalently linked
B. Oligosaccharides - 3-10 monosaccharides covalently linked to each other
C. Polysaccharides - polymers consisting of more than 10 chains of
monosaccharide units per molecule or disaccharide units (>10)
I. Monosaccharides
• The simplest of the carbohydrates that be cannot be further hydrolyzed.
• They are polyhydroxy aldehydes are called aldoses whereas polyhydroxy
ketones are called ketoses.
• Freely soluble in water but insoluble in non-polar solvents
• Most have a sweet taste
• Most monosaccharides of >4 C’s tend to have Cyclic structures
2 • The most abundant monosaccharide in nature is D-glucose
 Three criteria guide the classification of monosaccharides:
I. Whether the sugar contains aldehyde or ketone functional group
 If the carbonyl group is an aldehyde, the monosaccharide is an aldose.
 If the carbonyl group is ketone (usually at C-2) the sugar a ketose.
 The – ose suffix designates a carbohydrate, the aldo- and keto- prefixes
identify the kind of carbonyl group in the molecule
II. The number of carbon atoms in the chain.
 Those with three carbon atoms are trioses, with four tetroses, five
pentoses, six hexoses and seven carbon atoms are heptose.
III. The stereo-chemical configuration of the asymmetric carbon atom
farthest from the carbonyl group (D-sugar or L-sugar)
• Naturally occurring sugars (D-form, metabolizable sugars) have the
hydroxyl group at the bottom chirality center pointing to the right
• L-sugars (not metabolizable) have an S-configuration at the lowest chirality
center, with the bottom -OH group pointing to the left)

D-(+)-glyceraldehyde L-(-)-glyceraldehyde

• A molecule with n = no. of chirality centers has a maximum of 2n stereoisomers

 A. Configurations and Open Chain Structures of Aldoses
• D-sugar has the -OH group on the stereogenic center farthest from the
carbonyl on the right in a Fischer projection
• Diastereomers that differ in configuration at only one asymmetric carbon are
called epimers. E.g D-ribose and D-arabinose are C-2 epimers

4
 B. Configurations and Open Chain Structures of ketoses

• Naturally occurring ketoses have

the ketone group in the C-2-
position

• A ketose has one fewer asymmetric carbon than does an aldose with the
same number of carbon atoms.
• All carbohydrates except dihydroxyacetone contain one or more
stereogenic centers; therefore, they are optically active
•5 They can exist in either of two conformations
 Structure of Monosaccharides
The aldehyde and ketone moieties of the carbohydrates with five (Pentose)
and six (hexoses) carbons will spontaneously react with alcohol groups to
produce intramolecular hemiacetals or hemiketals, respectively.

• This results in the formation of five or six-membered rings.

• The five-membered ring structure resembles the organic molecule furan, derivatives
with this structure are termed furanoses.
• Those with six-membered rings resemble the organic molecule pyran and are
termed pyranoses.
 Haworth perspective formulas
• Representation of cyclic sugar structures are more accurately than in the
Fischer projections (commonly used for linear sugar structures).
• The six-membered ring is tilted to make its plane almost perpendicular to
that of the paper, with the bonds closest to the reader.
• If a –OH group is to the right in the Fischer projection, it is placed pointing
down (i.e., below the plane of the ring) in the Haworth perspective;
• If it is to the left in the Fischer projection, it is placed pointing up (i.e.,
above the plane) in the Haworth perspective.
• The terminal —CH2OH group projects upward for the D-enantiomer,
downward for the L-enantiomer
• Haworth projections represent the cyclic sugars as having essentially planar
rings, with the OH at the anomeric C1:
•  (OH below the ring)
• β (OH above the ring).
• Cyclization of glucose produces a new asymmetric center at C1.
• The two stereoisomers are called anomers,  & β.
 A. Cyclic Structure of Glucose
• Glucose forms an intra-molecular hemiacetal, as the C1 aldehyde & C5-
OH react, to form a 6-member pyranose ring, named after pyran.
• Cyclization of glucose produces a new asymmetric center at the former
carbonyl carbon (C1).

Haworth’s Pyranose Cyclic Form

Open chain Hemiacetal forming (Glucopyranose)
• A new chirality center is generated at the former carbonyl carbon and two
diastereomers, called anomers, are produced.
• Isomeric forms of monosaccharides that differ only in their configuration
about the hemiacetal or hemiketal carbon atom are called anomers.
• The two stereoisomers are called anomers, -Glucose & β-Glucose.
• The hemiacetal carbon atom is referred to as the anomeric center (carbon).
• The α and β anomers of D-glucose interconvert in aqueous solution by a
process called mutarotation, in which one ring form (α anomer) opens
briefly into the linear form, then closes again to produce the β-anomer.
• The specific rotation of the α-anomer solution decreases from +112.2
to +52.7, and that of the β anomer solution increases from +18.7 to +52.7
• When a sample of either pure anomer is dissolved in water, its optical
rotation slowly changes until it reaches a constant value of +52.7.
• Solution of β-D-glucose and a solution of α -D-glucose eventually form
identical equilibrium mixtures having identical optical properties (+52.7). .
• Two conformations, configurations (α and β) molecule are interconvertible
without the breakage of covalent bonds.
• Mutarotation occurs by a reversible ring-opening of each anomer to the
open-chain aldehyde, followed by re-closure

α-D-glucose β-Dglucose
Mpt =146oC and [α]D= +112.2 Mpt 148-155 oC & [α]D = +18.7.
 B. Cycli Structure of Fructose
• Ketohexoses (such as fructose) also occur as cyclic compounds with α and
β anomeric forms.
• 5-member ring furanose, by reaction of C2 keto group with the OH on C5.
• The hydroxyl group at C-5 reacts with the keto group at C-2, forming a
furanose ring containing a hemiketal linkage.
• D-fructose, exists in water solution as 70% b-pyranose, 2% a-pyranose,
0.7% open-chain, 23% b-furanose, and 5% a-furanose.
• In fructose the anomeric carbon is C-2, not
C-1 as in aldoses.

α –D-Fructofuranose or α –D-Fructose

10 β –D-Fructofuranose or β –D-Fructose
 Oxidation Reactions of Monosaccharides
• Carbohydrate that exists as a hemiacetal is in equilibrium with a small
amount of acyclic aldehyde, so it is oxidized to an aldonic acid.
• Three reagents (Tollens, Benedict’s, or Fehling’s) produce a characteristic
color change because the oxidizing agent is reduced to a colored product
• Carbohydrates that can be oxidized with these three reagent are called
reducing sugars.
• Carbohydrates that contain only acetal groups do not give positive tests
with Benedict’s or Tollens’ solutions, and called nonreducing sugars.
 Tollens reagent oxidizes aldehydes to carboxylic acids using Ag2O in
NH4OH, and forms a mirror of Ag as a by-product.
• Sugars that give a silver mirror with Tollens are called reducing sugars.
• The aldehyde group is oxidized, and the Ag+ is reduced to metallic silver.

D-glucose D-gluconic acid

 Benedict’s (copper (II) citrate) and Fehling’s solution (cupric (II) tartrate
complex ion) give brick red precipitates of Cu2O when they oxidize aldoses
• In alkaline solution ketoses are converted to aldoses which are then oxidized
by the cupric complexes.
• When the carbohydrate is oxidized, the blue Cu2+ ion is reduced to Cu+
(Cu2O), which forms a brick-red precipitate.
• Benedict’s reagent used in a self-test kit for sugar in the urine caused by
diabetes.
• Fructose, a ketohexose, is also a reducing sugar.
• In a basic solution such as Benedict's, the carbonyl group moves from
carbon 2 to carbon 1, so it can be oxidized as glucose.
• All aldoses are reducing sugars because they contain an aldehyde group, but
some ketoses are reducing sugars as well.

All carbohydrates that contain a hemiacetal group give positive tests.

• Both aldehyde and 1o alcohol of an aldose are oxidized to carboxy groups
treatment with warm HNO3 (strong oxidizing agent), forming an aldaric acid.
• Under these conditions, D-glucose is converted to D-glucaric acid.

D-glucose D-glucaric acid (an aldaric acid)

• Both aldoses and ketoses are oxidized to aldonic acids by Tollens reagent
• However, Tollens reagent oxidizes aldehydes but not ketones.
• Ketoses are oxidized b/c the reaction is carried out under basic conditions,
and in a basic solution, ketoses are converted into aldoses by enolization.

D-fructose enol of D-fructose, enol of D- D-glucose D-mannose

ketose glucose and enol of D-mannose an aldose an aldose
 8.2 Disaccharides
• Consist of two monosaccharides joined covalently by an O-glycosidic bond,
• Covalent bonds between the anomeric hydroxyl of a cyclic sugar and the
hydroxyl of a second sugar (or another alcohol) are termed glycosidic bonds.
• The reaction represents the formation of an acetal from a hemiacetal or ketal
from hemiketal and an alcohol (a -OH group of the 2nd sugar) and the resulting
compound is called a glycoside.
A. Maltose (malt sugar)
 Maltose contains two D-glucose residues joined by a glycosidic linkage
between C-1 (the anomeric carbon) of one glucose residue and C-4 of the
other glucose.
 A cleavage product of starch (amylose), is a disaccharide with an (1 4)
glycosidic link between C1 - C4 OH of two glucoses.
 Because it has a hemiacetal group (C-1 of the glucose residue on the right), it
is a reducing sugar.
 The glucose residue with the free –OH on anomeric carbon is capable of
existing in α- and β-pyranose forms.
 Also known as malt sugar.
 It is found in germinating grain (such as barley), and is formed during the
hydrolysis of starch to glucose during digestion.
  The configuration of the
+ H2O anomeric carbon atom in the
glycosidic linkage is α.

• The maltose molecule shown here retains a reducing hemiacetal at the C-1 not
involved in the glycosidic bond.
• Because mutarotation interconverts the α and β-forms of the hemiacetal, the bonds
at this position are sometimes depicted with wavy lines, as shown here, to indicate
that the structure may be either α or β.
B. Cellobiose,
• Obtained by partial hydrolysis of cellulose, consists of two β-D Glucose
units joined by a (β1→4) glycoside bond.
• Cellobiose differs from maltose in that the two glucose subunits are hooked
together by a (β1→4) glycosidic linkage.
• Reducing sugars because the right-hand subunit is a hemiacetal and
therefore is in equilibrium with their open-chain aldehyde that is easily
oxidized. β (1 → 4) glycosidic linkage

- H2O
+

β-form of Cellobiose
• Thus, the only difference in the structures of maltose and cellobiose is the
configuration of the glycosidic linkage.
• Like maltose, cellobiose exists in both α and β forms because the OH group
bonded to the anomeric carbon not involved in acetal formation
• Cellobiose is a reducing sugar because the subunit on the right is a
hemiacetal.
 C. Lactose (milk sugar) :
• Lactose is a disaccharide that occurs naturally in human (6.5%) and cow’s
milk (4.5%)
• Yields D-galactose and D-glucose on hydrolysis, occurs naturally in milk
• Joined by (β1→4) glycosidic linkage from the -OH group on C1 of galactose
and C4 of glucose.
• Reducing b/c it has free -OH(C1 is hemiacetal) bond at C1 of the β-D-glucose
• Lactose contains a hemiacetal, so it exists as a mixture of α and β anomers,
undergoes mutarotation.
β-OH

4 1 + 4 -H2O
1

β-OH

• The D-galactose subunit is an acetal, and that of D-glucose hemiaceta

• Lactose gives milk its sweetness
• It is digested by the enzyme lactase.
D. Sucrose, (table sugar) - obtained from sugar beets and sugarcane.
• Formed from D-glucose and D- fructose linked by a glycosidic bond
between C1 of the α-D-Glucose and C2 of β-D-Fructose (Glc
(α1→2β)Fru or Fru(β2→1α))
• Non reducing sugar because it does not have free –OH group at C1 of the
α-D-Glucose and C2 of β-D-Fructose.
• The –OH on the anomeric carbons of the glucose and fructose rings are
both used to form the glycosidic linkage.
• Sucrose does not exhibit mutarotation b/c the glycosidic bond is between
the anomeric carbon of glucose and the anomeric carbon of fructose.
• Sucrose contains two ketals but no hemiketal, so not in equilibrium with
the readily oxidized open-chain aldehyde or ketone in aqueous solution.
• Known as invert sugar b/c sign change from
+ 66.5o to -22o when hyrolized to 1:1 sugars
 8.3 Polysaccharides
• Polysaccharides, also called glycans, differ from each other in the identity
of their recurring monosaccharide units, in the length of their chains, in the
types of bonds linking the units, and in the degree of branching.
I. Homopolysaccharides contain only a single monomeric species;
• Starch and glycogen- serve as storage forms of monosaccharides that used
as fuels e.g., cellulose and chitin
II. Heteropolysaccharides contain two or more different kinds .
A) Starch
• Major storage form of D-glucose in plants cells as amylose (unbranched
starch) or amylopectin (branched starch ).
• Main carbohydrate found in the seeds and roots of plants such as corn,
rice, wheat, and potatoes
• Polymer composed of repeating glucose units joined in α-glycosidic
linkages.
• They are usually insoluble in water because of the high molecular weight,
but they can form thick colloidal suspensions with water.
• Glucose storage in polymeric form minimizes osmotic effects.
• Contains two types of glucose polymer, amylose and amylopectin
 I. Amylose -Comprises about 20% of starch molecules.
• Consists of long, unbranched chains of D-glucose (from 1000 to 2000
molecules) residues connected by (α1→4) linkages (as in maltose).
• The end of the polysaccharide with an anomeric C1 not involved in a
glycosidic bond is called the reducing end

II. Amylopectin -80%-90% of the starch in plants is in this form.

• Has a high molecular weight (up to 200 million) but unlike amylose is
highly branched.
• The glycosidic linkages joining
successive glucose residues by
α(1→4) and the branch points
occurring every 24 to 30 residues
with α (1→6) linkages.
B. Glycogen - the main storage polysaccharide of animal cells.
• Like amylopectin, glycogen is a polymer of (α1→4)-linked subunits of glucose,
with (α1→6) linked branches,
• But glycogen is more extensively branched (on average, every 8 to 12 residues)
and more compact than starch.
• Abundant in the liver, where it may constitute as much as 7% of the wet
weight; it is also present in skeletal muscle.
C. Cellulose
• Polymer consisting of linear, unbranched chains of D-glucose connected by
(β1→4) glycosidic linkages.
• Fibrous, tough, water-insoluble substance, is found in the cell walls of plants.
• Homopolysaccharide, consisting of 10,000 to 15,000 D-glucose units.
• Because of the β-linkages, cellulose form extended straight chains which H-
bond to each other, resulting in a very rigid structure

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 8.2 Amino-acids, peptides, and proteins
The Structure, Configuration and Properties of α-Amino Acids
The Structure Alpha-amino acids (α-Amino Acids)
Amino Acids are the building blocks for proteins and polypeptides.
Proteins and polypeptides are polymers of amino acids linked together by
what is called “ Peptide bond”.
There are about 300 amino acids occur in nature.
 Only 20 of them occur in proteins.
Nearly all proteins studied are made from the twenty standard amino acids.
They are difunctional (contain basic amino and acidic carboxyl group)
Have an amino group (NH2) bonded to the α-carbon of a carboxy group
(COOH), and so they are called α-amino acids.
H O They have a carboxyl group and an amino group bonded
R C C O- to the same carbon atom (α-carbon)
-Carbon All amino acids have a stereogenic center on the carbon
NH3
except glycine (R = H)
22 They have S- configuration (L-amino acids).
 Classification of amino acids
• According to the properties of their side chains (R-Groups)
• They differ from each other in their side chains (R groups) vary in structure,
size, and electric charge, and which influence the solubility aas in water
• The side chains of amino acids give them their different chemical properties
and allow proteins to have so many different structures
• Acidic Amino acids; - amino acids with an additional -COOH group in
the side. E.g. aspartic acid glutamic
• Basic amino acids; - amino acids with an additional basic N atom in the
side chain. E.g. lysine, arginine, and histidine
• Hydroxyl groups containing amino acids side chain -they are called
hydroxy amino acids e.g. serine and threonine
• Sulfur containing amino acids side chain e.g cysteine and methionine
• Aliphatic side chain amino acids with -e.g. glycine, alanine, valine,
leucine and isoleucine
• Aromatic rings containing e.g. phenylalanine, tyrosine and tryptophan
• Imino acids e.g. proline
• Amide containing amino acids e.g. asparagine and glutamine
• All-amino acids are α-amino acids except proline (a cyclic an imino acid
23 not amino acid, proline has a secondary amino group).
Nonpolar,
pKa pKa
aliphatic R groups Symbol Structure*
(COOH) (NH2)
Amino Acids

Methionine* Met-M 2.28 9.21

Glycine Gly- G 2.34 9.60

Alanine Ala- A 2.34 9.69

Neutral Sulfur containing amino
acids:
Proline
(Imino Acids)
Pro – P 1.99 10.60  Methionine -has a nonpolar
thioether group in its side chain
 C & S have nearly equal EN
Valine* Val- V 2.32 9.62 and S is about the size of a
methylene group).
R is isobutyl in leucine and
Leucine* Leu- L 2.36 9.60 sec-butyl in isoleucine but
branching is different:
leucine →branching occurs
on γ carbon
Isoleucine* Ile – I 2.36 9.60
isoleucine→ branching
24 occurs on β- carbon
Aromatic amino acids:
 Their aromatic side chains, are relatively nonpolar (hydrophobic).
 All can participate in hydrophobic interactions except tyrosine.
Aromatic R groups pKa pKa pK R a)Phenyl alanine:
Symbol Structure*
Amino Acids (COOH) (NH2) Group
 It is alanine in which one H
of CH3 is substituted with
phenyl group.
Phe – F
 So it’s called phenyl alanine
Phenylalanine* 1.83 9.13

b)Tyrosine: - some polar

 Para-hydroxylphenyl alanine
 Classified as phenolic amino
Tyrosine Tyr- Y 2.20 9.11 10.07
acid
 The -OH group can form H-
bonds, and important in some
enzymes.
c)Tryptophan:
 It contains indole ring
Tryptophan* Trp-W 2.83 9.39
 it is classified as heterocyclic
amino acid
25
Polar, Uncharged R Groups
 The R groups of these amino acids are more soluble in water, or more hydrophilic,
 They contain functional groups that form hydrogen bonds with water.
Polar,
Uncharged R pKa pKa pK R
Groups Amino
Acids
Symbol Structure*
(COOH) (NH2) Group  The polarity of serine and
threonine is contributed by their
Serine Ser – S 2.21 9.15 ~13 hydroxyl groups.
 The polarity of of asparagine
and glutamine by their amide
Threonine* Thr – T 2.09 9.10 ~13 groups
 The polarity cysteine is
contributed by its sulfhydryl
Cysteine Cys- C 1.96 10.28 8.18 group
• It is a weak acid
• Can make weak hydrogen
Asparagine Asn- N 2.02 8.80 bonds with oxygen or nitrogen.
 Asparagine and glutamine are
the amides of two amino acids
also found in proteins
Glutamine Gln- Q 2.17 9.13

26
Polar Positively Charged (Basic) R Groups (Basic amino acids)
Basic Amino pKa pKa pK R
Symbol Structure*
Acids (COOH) (NH2) Group
 They are basic amino acids:
 Contain two or more NH2 groups or
nitrogen atoms that act as base
Arginine* Arg- R 2.17 9.04 12.48  At physiological pH, basic amino
acids will be positively charged.
 Arginine has a positively charged
guanidinium (guanidino) group
 Lysine has a second primary
amino group at the ε-position on
Lysine* Lys- K 2.18 8.95 10.53 its aliphatic chain;
 Histidine
 has an aromatic imidazole group.
 basic heterocyclic amino acids
 The only common amino acid
Histidine* His- H 1.82 9.17 6.0 having an ionizable side chain
with a pKa near neutrality
27
Negatively Charged (Acidic) R Groups
 The two amino acids having R groups with a net negative charge at pH 7.0 are
aspartate and glutamate, each of which has a second carboxyl group.
Acidic amino pKa pKa pK R
Symbol Structure*
acids (COOH) (NH2) Group
 They are acidic
Amino acids:
Aspartic Acid Asp- D 1.88 9.60 3.65  at physiological pH
will carry negative
charge.

Glutamic
Glu- E 2.19 9.67 4.25
Acid

• The amino acids are almost always called by their common names. For example,
 Glycine got its name because of its sweet taste (glykos is Greek for “sweet”)
 Valine, like valeric acid, has five carbon atoms.
 Asparagine was first found in asparagus
28
28
 Tyrosine was isolated from cheese (tyros is Greek for “cheese”)
 Properties of α-amino acids
A) Configuration and Optical Properties of α-Amino Acids
 All amino acids except glycine (R = H) have at least one stereogenic center
 The amino acids that occur naturally in proteins differ in the identity of the R
group bonded to the α-carbon
 Naturally occurring α-amino acids have S-configuration (L-amino
 All AAs (except glycine) are optically active i.e they can rotate plane
polarized light.
 Serine is used as a reference for configuration of AAs as one of the
enantiomers;
L-form with –NH2 on the left side of -carbon,
• The predominant form the only form of AAs that occurs in proteins and
• It is metabolizable
D-form, with –NH2 on the right side of -carbon
• Unmetabolizable amino and found in the peptides of bacterial cell walls and
antibiotics.

29
 B) Acid–Base Properties of α-Amino acid
Carboxylic as well as the amino groups of AAs are ionizable.
 They undergo an intramolecular acid-base reaction to form a dipolar ion,
also known as a zwitterion:
 The dipolar ion has both an acidic group, the ammonium cation, and a
basic group, the carboxylate anion, so it can act as either an acid or a
base. Such compounds are termed amphoteric.
 In alkaline pH, the carboxylic ‘–CO2H’ group of an AA gets dissociated
to release a proton and acquires a negative charge (CO2−)
 In acidic pH, the –NH2 group ionizes into charged amino groups (NH3+).

30
30
 Isoelectric Point (pI) / Isoelectric pH:
 The specific pH at which an amino acid (or a protein) would carry equal
negatively charged –COO- and positively charged –NH3+ groups.
 Is the pH at which an amino acid exists primarily in its neutral form.
pI (isoelectric point) = pH at which there is no net charge
 In this state the molecule carries no net charge or is ‘isoionic’ and is called
Zwitterion (meaning ‘equal charge ion’).
Since at pI, the AAs are electrically neutral, they will not migrate in electric
field and are readily precipitated.
The pI is a specific characteristic for each AA or protein.
pI for Mono amine and dicarboxylic group is : pI: ½ (pKacid1 + pKacid2)
pI for di amine and monocarboxylic group is : pI: ½ (pKamino1 + pKamino2)

31
 Synthesis of α-amino acids
Amidomalonate Synthesis
• A more general method for preparation of α-amino acids, using key reagent diethyl
acetamidomalonate, a derivative of malonic ester
• Formation of enolate ion by treatment with base, followed by SN2 alkylation
• Hydrolysis esters occurs when the alkylated product is warmed with aqueous acid,
and decarboxylation then takes place to yield an α-amino acid

Reductive Amination of α-Keto Acids

• Reductive amination of an α -keto acid with ammonia and a reducing agent.
• The reaction proceeds through formation of an intermediate imine
H2
Pd
32
• The imine is reduced to an amine by hydrogen and a palladium catalyst.
• Under these conditions, the carboxylic acid is not reduced
• The product is a racemic acid

The Hell–Volhard–Zelinsky reaction

• Effective method for introducing bromine at α carbon of a carboxylic acid.
• The racemic α-bromo of acid is converted to a racemic α-amino acid by
direct amination, using a large excess of ammonia
 The Strecker Synthesis
• Treating an aldehyde with ammonia and hydrogen cyanide produces an α-
aminonitrile an an intermediate.
• Hydrolysis of the nitrile group of the α-aminonitrile convert into carboxylic
acid function completes the synthesis an α-amino acid.

Example

2-(p-hydroxyphenyl)acetaldehyde
•34 Outline the steps in the preparation of valine by the Strecker synthesis
 Peptides and Proteins
 20 amino acids are commonly found in protein.
 These 20 amino acids are linked together through “peptide bond forming
peptides and proteins (what’s the difference?).
 The chains containing less than 50 amino acids are called “peptides”,
while those containing greater than 50 amino acids are called “proteins”.
 Proteins are linear polymer of L-amino acids.
Peptide bond formation:
 α-carboxyl group of one amino acid (with side chain R1) forms a covalent
peptide bond with α-amino group of another amino acid ( with the side
chain R2) by removal of a molecule of water.
 Dipeptide - two amino acids linked by one peptide bond).
 Tripeptide- Dipeptide can then forms a second peptide bond with a third
amino acid (with side chain R3) or three amino acids linked by two peptide
bonds
 Repetition of this process generates a polypeptide or protein of specific
amino acid sequence
35Each polypeptide chain starts on the left side by free amino group of the
first amino acid enter in chain formation, termed as (N- terminus)
 Each polypeptide chain ends on the right side by free COOH group of the
last amino acid and termed (C-terminus).
• Octapeptides  Links of eight amino acids
Examples: Two hormones; oxytocine and vasopressin (ADH).
• Polypeptides  Link of 10- 50 amino acids: e.g. Insulin hormone
36
36
 Disulfide Bonds
• When thiols are oxidized under mild conditions, they form disulfides.
• A disulfide is a compound with an bond

• An oxidizing agent commonly used for this reaction is (or ) in a basic

solution.

• Cysteine is an amino acid that contains a thiol group.

• Two cysteine molecules therefore can be oxidized to a disulfide.
• This disulfide is called cystine

37
 Natural product
• A compound synthesized by a plant, microorganism or an animal.
• Natural products are the source of the most complex and fascinating
chemical structures.
• A natural product is a chemical compound or substance produced by a
living organism - that is found in nature
• In a narrow sense, natural products often means secondary metabolites that
have intriguing bioactivities.
• They are organic compounds generated in organisms (metabolites) that are
not essential in the reproduction, development, or normal growth.
• Natural products often means secondary metabolites that have intriguing
bioactivities
• Humans use secondary metabolites discovered from nature as medicines,
agents, and favorings
• Secondary metabolites are chemicals synthesised by plants but are not
directly used by them, but are used indirectly by man as a source of
pharmaceutical preparations
• Metabolites are naturally-occurring organic compounds synthesised by
38 plants, through metabolic activities in plants, aided by enzymes
 Terpenes
• Terpenes are hydrocarbons of plant origin of the general formula (C5H8)n as
well as their oxygenated, hydrogenated and dehydrogenated derivatives.
• They can be hydrocarbons, or they can contain oxygen and be alcohols,
ketones, or aldehydes, acids and esters
• Terpenes are lipids composed of repeating 5-carbon units called isoprene
units.
• Isoprene unit has 5 carbons: 4 in a row, with a 1-carbon branch on a middle
• Oxygen-containing terpenes are sometimes called terpenoids.
• Certain terpenes and terpenoids have been used as spices, perfumes, and
medicines for many thousands of years
• Terpenoids are abundantly available in volatile oils.
• Many essential oils, a group of compounds isolated from plant sources by
distillation, are terpenes

39
• They contained carbon atoms in multiples of 5.
• These naturally occurring compounds contain 10, 15, 20, 25, 30, and 40
carbon atoms, which suggests that there is a compound with five carbon
atoms that serves as their building block
• Their structures are consistent with the assumption that they were made by
joining together isoprene units, usually in a head-to-tail fashion.
• (The branched end of isoprene is called the head, and the unbranched end is
called the tail.)
• Isoprene is the common name for 2-methyl-1,3-butadiene, a compound
containing five carbon atoms.
• That isoprene units are linked in a head-to-tail fashion to form terpenes is
known as the isoprene rule

α-farnesene a sesquiterpene found in the

40
waxy coating on apple skins
 Terpenes are classified according to the number of carbons they contain
Carbon Classification No. of Carbon Classification No. of isoprene
atoms isoprene units atoms units
10 Monoterpenes 2 25 Sesterterpenes 5
15 Sesquiterpenes 3 30 Triterpenes 6
20 Diterpenes 4 40 Tetraterpenes 8

Carvone Squalene
spearmint oil a monoterpene triterpene, precursor of steroid molecules

β-carotene (Tetraterpenes Carotenoids)

• β-carotene compound that causes carrots and apricots to be orange, are
41 examples of carotenoids, carotenoids are tetraterpenes.
 Steroids
• The steroids are a group of tetracyclic lipids, which contain Sterane ring
three cyclohexane (three six-membered rings) and one cyclopentane rings
• All steroids contain a tetracyclic ring system and the four fused rings are
designated A, B, C, and D beginning at the lower left.
• Many of which are biologically active, many hormones are steroids.
• Because steroids are nonpolar compounds, they are lipids.
• Their nonpolar character allows them to cross cell membranes, so they can
leave the cells in which they are synthesized and enter their target cells.
• The most abundant steroids are sterols which are steroid alcohols

42 Cholesterol
 • Rings can be trans fused or cis fused, but trans fused rings are more stable
• Most naturally occurring steroids, the A , B, C and D rings are trans fused.
• The substituents at the ring fusion can be arranged cis or trans.

A and B rings are trans fused A and B rings are cis fused
• Many steroids have methyl groups at the C-10 and C-13 positions.
• These are called angular methyl groups.
• When steroids are drawn, both angular methyl groups are shown to be
above the plane of the steroid ring system.
• Substituents on the same side of the steroid ring system as the angular
methyl groups are indicated by a solid wedge and those on the opposite
side of the plane of the ring system are (indicated by a hatched wedge).
• The most abundant member of the steroid family in animals is cholesterol,
the precursor of all other steroids.
•
43 The most abundant steroids are sterols which are steroid alcohols
 • In humans, most steroids function as hormones, chemical messengers
• There are two types of female sex hormones, estrogens and progestins.
• The male sex hormones are called androgens
 Male Sex Hormones- Androstanedione is a precursor

 Female Sex Hormones

• Estradiol and estrone are estrogens synthesized in the ovaries.
• Progesterone is often called the “pregnancy hormone

44
Eestradiol Estrone Progesterone
44
 Adrenocortical steroids
• At least 28 different hormones have been isolated from the adrenal cortex,
part of the adrenal glands that sit on top of the kidneys.

Cortisone Cortisol Aldosterone

• All these compounds are synthesized in the outer layer of the adrenal gland.
• Cortisone and cortisol serve as anti-inflammatory agents and they also
regulate carbohydrate metabolism.
• Aldosterone regulates blood pressure and volume by controlling the
concentration of Na+ and K+ in body fluids

45