Heterocyclic and Bioorganic Chemistry Unit IV Bioorganic ... · Bioorganic chemistry is the area that includes metabolism, biosynthesis, transformation, ... molecules and materials

Unit IV: Bioorganic Chemistry

Bioorganic chemistry studies the biological processes using

synthesis and kinetics in a biological systems and principles

combines organic chemistry and biochemistry

chemistry.

Bioorganic chemistry is the area that includes metabolism, biosynthesis, transformation, elimination reactions of

organic elements (Ex: oxygen, nitrogen, h

hydrolysis, phosphorylation, etc. It can also take inspiration f

molecules and materials for non-biological applications.

Alkaloids

Introduction:

Alkaloids are naturally occurring basic hete

active. Some synthetic compounds of similar structure are also termed

and nitrogen, alkaloids may also contain oxygen, sulphur and more rarely, other elements such

bromine and phosphorus. Although the name

properties. This group also includes some related compounds with neutral

can be found in one or more parts of the plant (leaves, fruits, seeds or whole plant). Generally, these are insolubl

in water but can be extracted by organic solvents in alkaline media. The most important

interest are: opium, atropine, cocaine, strychnine, nicotine, aconite, ergot, digitalis

Alkaloids are also produced by a large variety of organisms including

range of pharmacological activities including anti

(e.g., homoharringtonine), cholinomimetic

(e.g., quinidine), analgesic (e.g. morphine

(e.g. piperine). Many have found use in traditional

Other alkaloids possess psychotropic (e.g.

theobromine) and have been used in entheogenic

atropine, tubocurarine). Although alkaloids

they almost uniformly evoke a bitter taste

� True (Typical) alkaloids that are derived from amino acids and have nitrogen in the ring. e.g., Atropine.

� Proto Alkaloids that are derived from amino acids and do not have nitrogen in the ring. e.g., Ephedrine.

� Pseudo Alkaloids that are not derived from a

� False Alkaloids that are non-alkaloids give false positive reaction with alkaloidal reagents.

On the basis of source, alkaloids can be classified as:

Alkaloids can also be classified as:

(i) Pyrrolidine Alkaloids:

Pyrrolidine alkaloids contain pyrrolidine ring system. Examples:

Pyrrolidine Hygrine

Unit IV: Bioorganic Chemistry

biological processes using chemical methods. It broadly describ

systems and principles. It is a rapidly growing scientific discipline

biochemistry. Biochemistry aims at understanding biological

includes metabolism, biosynthesis, transformation, elimination reactions of

(Ex: oxygen, nitrogen, hydrogen, etc). The reactions include oxidation, reduction, hydroxylation,

It can also take inspiration from biology for the design and synthesis of novel

biological applications.

basic heterocyclic nitrogenous compounds of plant origin that are physiologically

active. Some synthetic compounds of similar structure are also termed alkaloids. In addition to

may also contain oxygen, sulphur and more rarely, other elements such

Although the name alkaloid means alkali-like, some alkaloids do not exhibit alkaline

This group also includes some related compounds with neutral and even weakly acidic properties. They

can be found in one or more parts of the plant (leaves, fruits, seeds or whole plant). Generally, these are insolubl

in water but can be extracted by organic solvents in alkaline media. The most important alkaloids

opium, atropine, cocaine, strychnine, nicotine, aconite, ergot, digitalis and cannabis.

are also produced by a large variety of organisms including bacteria, fungi and animals

activities including anti-malarial (e.g., quinine), antiasthma (e.g., ephedrine), anticancer

cholinomimetic (e.g., galantamine), vasodilatory (e.g., vincamine

morphine), anti-bacterial (e.g. chelerythrine) and anti-hyperglycemic activities

traditional or modern medicine or as starting points for

(e.g. psilocin) and stimulant activities (e.g., cocaine

entheogenic rituals or as recreational drugs. They can be

alkaloids act on a diversity of metabolic systems in humans and other animals,

bitter taste. Generally alkaloids are classified as:

that are derived from amino acids and have nitrogen in the ring. e.g., Atropine.

that are derived from amino acids and do not have nitrogen in the ring. e.g., Ephedrine.

that are not derived from amino acids but have nitrogen in the ring. e.g., Caffeine.

alkaloids give false positive reaction with alkaloidal reagents.

can be classified as: natural, semi-synthetic and synthetic alkaloids

contain pyrrolidine ring system. Examples: hygrine, cuscohygrine and stachydrine.

Cuscohygrine Stachydrine

The first individual alkaloid, morphine, was isolated in

1804 from the opium poppy (Papaver somniferum

describes the structures,

scientific discipline that

understanding biological processes using

includes metabolism, biosynthesis, transformation, elimination reactions of

ydrogen, etc). The reactions include oxidation, reduction, hydroxylation,

rom biology for the design and synthesis of novel

rocyclic nitrogenous compounds of plant origin that are physiologically

In addition to carbon, hydrogen

may also contain oxygen, sulphur and more rarely, other elements such as chlorine,

do not exhibit alkaline

and even weakly acidic properties. They

can be found in one or more parts of the plant (leaves, fruits, seeds or whole plant). Generally, these are insoluble

alkaloids of toxicological

cannabis.

animals. They have a wide

malarial (e.g., quinine), antiasthma (e.g., ephedrine), anticancer

vincamine), anti-arrhythmic

hyperglycemic activities

or as starting points for drug discovery.

cocaine, caffeine, nicotine,

. They can be toxic too (e.g.

sity of metabolic systems in humans and other animals,

that are derived from amino acids and have nitrogen in the ring. e.g., Atropine.

that are derived from amino acids and do not have nitrogen in the ring. e.g., Ephedrine.

mino acids but have nitrogen in the ring. e.g., Caffeine.

alkaloids give false positive reaction with alkaloidal reagents.

synthetic alkaloids.

stachydrine.

Stachydrine

, was isolated in

Papaver somniferum)

(ii) Piperidine Alkaloids:

Piperidine alkaloids contain piperidine

which is the Latin word for pepper. Although,

representative structure element within many pharmaceuticals and

objectionable odour described. Examples:

Piperidine Piperine

(iii) Pyridine-Pyrrolidine Alkaloids:

These alkaloids contain both pyridine and

Pyridine-pyrrolidine Nicotine Mysomine

(iv) Pyridine-Piperidine Alkaloids:

These alkaloids contain both pyridine and piperidine ring system. Examples:

4-Piperidine-4-yl-pyridine

(v) Quinoline Alkaloids:

These alkaloids contain quinoline ring system. Examples:

Quinoline

(vi) Isoquinoline Alkaloids:

These alkaloids contain isoquinoline ring system. Examples:

Isoquinoline Morphine

ring system. The name piperidine comes from the genus name Piper,

pepper. Although, piperidine is a common organic compound, it is best known as a

representative structure element within many pharmaceuticals and alkaloids. These are colourless liquid with

Examples: piperine, coniine and solenopsin.

Piperine Coniine Solenopsin

These alkaloids contain both pyridine and pyrrolidine ring system. Examples: nicotine and mysomine.

pyrrolidine Nicotine Mysomine

These alkaloids contain both pyridine and piperidine ring system. Examples: anabasin and anatabine.

Anabasin Anatabine

These alkaloids contain quinoline ring system. Examples: quinine and primaquinine.

Quinoline Quinine Primaquinine

These alkaloids contain isoquinoline ring system. Examples: morphine and papaverine.

Isoquinoline Morphine Papaverine

comes from the genus name Piper,

is a common organic compound, it is best known as a

. These are colourless liquid with

pyrrolidine ring system. Examples: nicotine and mysomine.

anabasin and anatabine.

Anatabine

(vii) Indole Alkaloids:

These alkaloids contain indole ring system

canthinone.

Indole Serotonin

Generally, amino acids such as ornithine, lysine, phenylalanine, tyrosine, tryptophan and histidine

for most of the alkaloids.

Ornithine Lysine

Tyrosine Tryptophan

Some common features of alkaloids are:

These are found in plants although a few are of animal origin.

Most alkaloids contain oxygen in their molecular structure; those compounds are usually colorless crystals at

ambient conditions. Oxygen-free alkaloids, such as

liquids. Some alkaloids are coloured, like

Most alkaloids are weak bases, but some, such as

Many alkaloids dissolve poorly in water but readily in

dichloroethane. Caffeine, cocaine, codeine

whereas others, including morphine and

Alkaloids and acids form salts of various strengths. These

and ethanol and poorly soluble in most organic solvents. Exceptions include

is soluble in organic solvents and the water

Most alkaloids have a bitter taste or are poisonous when ingested.

Synthesis of Alkaloids:

Most alkaloids are synthesized from a few common amino acids (such as ornithine, lysine, phenylalanine,

tyrosine, tryptophan, histidine, aspartic acid

synthesis of various classes of alkaloids, including synthesis of

Synthesis of Schiff’s Bases:

Schiff’s bases can be obtained by

reacting amines with ketones or

aldehydes producing C=N bonds.

Such reactions may take place within

a molecule, such as in the synthesis

of piperidine:

Mannich Reaction:

contain indole ring system derived from L-tryptophan. Examples: Serotonin

Harmine Canthinone

Generally, amino acids such as ornithine, lysine, phenylalanine, tyrosine, tryptophan and histidine

Ornithine Lysine Phenylalanine

Tyrosine Tryptophan Histidine

plants although a few are of animal origin.


free alkaloids, such as nicotine or coniine, are typically volatile, colorless, oily

Some alkaloids are coloured, like berberine (yellow) and sanguinarine (orange).

Most alkaloids are weak bases, but some, such as theobromine and theophylline, are amphoteric

Many alkaloids dissolve poorly in water but readily in organic solvents, such as diethyl ether

codeine and nicotine are slightly soluble in water (with a solubility of

and yohimbine are very slightly water-soluble (0.1–1 g/L).

Alkaloids and acids form salts of various strengths. These salts are usually freely soluble in water

and poorly soluble in most organic solvents. Exceptions include scopolamine

is soluble in organic solvents and the water-soluble quinine sulfate.

Most alkaloids have a bitter taste or are poisonous when ingested.

are synthesized from a few common amino acids (such as ornithine, lysine, phenylalanine,

aspartic acid and anthranilic acid). There are a few typical reactions involved in the

synthesis of various classes of alkaloids, including synthesis of Schiff bases and Mannich reaction

Serotonin, harmine and

Canthinone

Generally, amino acids such as ornithine, lysine, phenylalanine, tyrosine, tryptophan and histidine are precursor

Phenylalanine

Histidine


, are typically volatile, colorless, oily

amphoteric.

diethyl ether, chloroform or 1,2-

are slightly soluble in water (with a solubility of ≥1g/L),

1 g/L).

salts are usually freely soluble in water

scopolamine hydrobromide, which

are synthesized from a few common amino acids (such as ornithine, lysine, phenylalanine,

anthranilic acid). There are a few typical reactions involved in the

Mannich reaction.

An integral component of the Mannich reaction

which plays the role of the nucleophile in the

and the carbonyl.

The Mannich reaction can proceed both inter

Dimer alkaloids

In addition to the described above monomeric alkaloids, there are also

alkaloids formed upon condensation of two, three and four monomeric alkaloids. Dimeric alkaloids are usually

formed from monomers of the same type through the following mechanisms:

• Mannich reaction ( voacamine)

• Michael reaction (villalstonine)

• Condensation of aldehydes with amines (toxiferine)

• Oxidative addition of phenols (dauricine, tubocurarine)

• Lactonization (carpaine).

Synthesis of Indole Alkaloids:

Biogenetic precursor of all indole alkaloids is the

is de-carboxylation of tryptophan to form

by methylation with the participation of coenzyme

(i) Synthesis of Serotonin:

In the synthesis of serotonin, the intermediate product is 5

to form 5-hydroxytryptamine (serotonin).

Mannich reaction, in addition to an amine and a carbonyl compound, is a

which plays the role of the nucleophile in the nucleophilic addition to the ion formed by the reaction of the amine

can proceed both inter-molecularly and intra-molecularly:

Dimer alkaloids

In addition to the described above monomeric alkaloids, there are also dimeric and even trimeric and


the same type through the following mechanisms:

Condensation of aldehydes with amines (toxiferine)

Oxidative addition of phenols (dauricine, tubocurarine)

ogenetic precursor of all indole alkaloids is the tryptophan amino acid. For most of them, the first synthesis step

of tryptophan to form tryptamine. Dimethyltryptamine (DMT) is form

coenzyme of S-adenosyl methionine (SAM).

, the intermediate product is 5-hydroxytryptophan, which is in turn de

hydroxytryptamine (serotonin).

compound, is a carbanion,

to the ion formed by the reaction of the amine

even trimeric and tetrameric


amino acid. For most of them, the first synthesis step

(DMT) is formed from tryptamine

hydroxytryptophan, which is in turn de-carboxylated

Synthesis of Morphine:

Gates Synthesis:

Gates' total synthesis is the first morphine total synthesis

steps and proceeded in 0.06% over all yield.

Gates' total synthesis is the first morphine total synthesis (Marshall D. Gates, Jr. in 1952) which took a total of 31

steps and proceeded in 0.06% over all yield.

which took a total of 31

Rice Synthesis:

Dihydrocodeinone synthesis of K. C. Rice is one of the most efficient and proceeds in 30% overall yield in 14 steps.

Terpenoids

Introduction:

Terpenoids, sometimes called isoprenoids, are a large and diverse class of naturally occurring organic compounds.

These are similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of

ways. Most are multicyclic structures that differ from one another not only in functional groups but also in their

basic carbon skeletons. These lipids can be found in all classes of living things and are the largest group of natural

products. About 60% of known natural products are terpenoids.

Plant terpenoids are used extensively for their aromatic qualities and play a role in traditional herbal remedies.

Terpenoids contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, the yellow color

in sunflowers, and the red colour in tomatoes. Well-known terpenoids include citral, menthol, camphor, salvinorin

A in the plant Salvia divinorum, the cannabinoids found in cannabis, ginkgolide and bilobalide found in Ginkgo

biloba, and the curcuminoids found in turmeric and mustard seed.

Terpenoids are volatile substances which give plants and flowers their fragrance. They occur widely in the leaves

and fruits of higher plants, conifers, citrus and eucalyptus. By the modern definition, terpenoids are the

hydrocarbons of plant origin of the general formula (C5H8)n as well as their oxygenated, hydrogenated and

dehydrogenated derivatives.

According to isoprene rule thermal decomposition of terpenoids give isoprene as one of the product. The

isoprene rule stats that the terpenoid molecules are constructed from two or more isoprene unit

[CH2=C(CH3)CH=CH2]. Terpenoids can be classified according to the number of isoprene units used as:

• Hemiterpenoids, 1 isoprene unit (5 carbons)

• Monoterpenoids, 2 isoprene units (10C)

• Sesquiterpenoids, 3 isoprene units (15C)

• Diterpenoids, 4 isoprene units (20C) (e.g. ginkgolides)

• Sesterterpenoids, 5 isoprene units (25C)

• Triterpenoids, 6 isoprene units (30C) (e.g. sterols)

• Tetraterpenoids, 8 isoprene units (40C) (e.g. carotenoids)

• Polyterpenoid with a larger number of isoprene units

Each class can be further subdivided into subclasses according to the number of rings present in structure.

(i) Acyclic Terpenoids: They contain open structure.

(ii) Monocyclic Terpenoids: They contain one ring in the structure.

(iii) Bicyclic Terpenoids: They contain two rings in the structure.

(iv) Tricyclic Terpenoids: They contain three rings in the structure.

(v) Tetracyclic Terpenoids: They contain four rings in the structure.

Synthesis of Terpenoids:

Menthol:

Introduction:

Menthol is the major constituent of Mentha Piperita. It is used as an antiseptic and anesthetic. Menthol (also

called peppermint camphor or mint camphor) is the major constituent of peppermint oil and is responsible for its

odour and taste and the cooling sensation when applied to the skin. It is ingredient in cold balms. Menthol is

optically active compound with mol. formula C10H20O.

Synthesis of Menthol:

By Takasago Process:

Menthol is manufactured by Takasago International Corporation. The process involves an asymmetric

synthesis developed by a team led by Ryoji Noyori, who won 2001 Nobel Prize for Chemistry. In this process a (S)-

DINAP ruthenium complex catalysed isomerization is the key step. Addition of lithium amide to myrcene gave an

addition compound that was isomerised using a chiral ruthenium catalyst. Hydrolysis of the resulting enamine

gave an aldehyde citronellal in high enantiomeric purity. This was cyclized by Lewis catalyst. Catalytic reduction of

the olefin gave (-)-Menthol.

Chemical Properties of Menthol:

Menthol chemically trigger the cold-sensitive TRPM8 receptors in the skin is responsible for the well-known

cooling sensation it provokes when inhaled, eaten, or applied to the skin.[1]

In this sense, it is similar to capsaicin,

the chemical responsible for the spiciness of hot chilis (which stimulates heat sensors, also without causing an

actual change in temperature). Analgesic properties of Menthol are mediated through a selective activation of κ-

opioid receptors. Menthol also blocks voltage-sensitive sodium channels, reducing neural activity that may

stimulate muscles. A study showed that topical absorption of ibuprofen is not increased by menthol, but does

DINAP Ruthenium Complex

note the complementary effect of the menthol as a pain reliever i

as GABAA receptor positive allosteric modulator

also shares anaesthetic properties similar to

widely used in dental care as a topical antibac

of streptococci and lactobacilli.

Menthol reacts in many ways like a normal secondary alcohol. It is oxidised to

as chromic acid or dichromate, though under some conditions the oxidation can go further and break open the

ring. Menthol is easily dehydrated to give mainly 3

pentachloride (PCl5) gives menthyl chloride.

Proteins:

Introduction:

Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells

and are required for the structure, function

constructed from one set of twenty amino acids and a particular protein's design helps with its specific function in

the cell. Antibodies, contractile proteins, and enzymes are three important types of specialized proteins found in

living organisms. Occurring in the cytoplasm, translation is the process through which proteins are synthesized.

Each protein within the body has a specific function,

In total, there are seven types of proteins

insulin. While proteins have many diverse functions, all are typically constructed from one set of 20

The structure of a protein may be globular or fibrous, and the design helps each protein with their

particular function.

Structure of Protein:

Amino acids are the building blocks of

polypeptide. Amino acids consist of a carboxylic acid (COOH), an amine group (NH

group.

Primary structure is the simplest type of protein

up a protein.

Secondary structure is a bit more complex and refers to the arrangement or conformation of the amino acids.

There are two main types of secondary structures

spiral staircases and they are stabilized by hydrogen

in α-helices than others. Alanine is a small amino acid and is more often found in α

found, but is less common. In this case, R groups are

Bulkier amino acids, such as proline, are never fo

forms: parallel and anti-parallel. Parallel sheets occur when neighboring chains run in the same direction, and they

run in the opposite direction in anti-parallel β

sheets. Small amino acids are common, while large amino acids destabilize β

stable because they hydrogen bonds are distorted instead of

note the complementary effect of the menthol as a pain reliever itself. Some studies show that menthol acts

receptor positive allosteric modulator and increases GABAergic transmission in PAG neurons.

properties similar to propofol, by modulating same sites of GABAA

widely used in dental care as a topical antibacterial agent, effective against several types

s like a normal secondary alcohol. It is oxidised to menthone by oxidising agents such

though under some conditions the oxidation can go further and break open the

ring. Menthol is easily dehydrated to give mainly 3-menthene, by the action of 2% sulfuric acid

) gives menthyl chloride.

are large, complex molecules that play many critical roles in the body. They do most of the work in cells

red for the structure, function and regulation of tissues and organs of the body


Antibodies, contractile proteins, and enzymes are three important types of specialized proteins found in

ing in the cytoplasm, translation is the process through which proteins are synthesized.

Each protein within the body has a specific function, from cellular support to cell signaling and cellular locomotion.

In total, there are seven types of proteins, including antibodies, enzymes and some types of

While proteins have many diverse functions, all are typically constructed from one set of 20


Amino acids are the building blocks of proteins and they are linked by peptide bonds to form a

Amino acids consist of a carboxylic acid (COOH), an amine group (NH2), a carbon and a variable R

protein structure. This is simply the linear chain of amino acids that make

is a bit more complex and refers to the arrangement or conformation of the amino acids.

secondary structures: α-helix and β-sheet. The α-helices are right handed, resemble

spiral staircases and they are stabilized by hydrogen bonds. Certain types of amino acids are much more common

Alanine is a small amino acid and is more often found in α-helices.

In this case, R groups are external while the hydrogen bonds are

Bulkier amino acids, such as proline, are never found and would destabilize the α-helix.

Parallel sheets occur when neighboring chains run in the same direction, and they

parallel β-sheets. Instead of the R groups being external

Small amino acids are common, while large amino acids destabilize β-sheets. Parallel β

ause they hydrogen bonds are distorted instead of linear, like in antiparallel β-sheets.

Some studies show that menthol acts

transmission in PAG neurons. Menthol

A receptor. Menthol is

terial agent, effective against several types

by oxidising agents such

though under some conditions the oxidation can go further and break open the

sulfuric acid. Phosphorus

are large, complex molecules that play many critical roles in the body. They do most of the work in cells

of the body. The typical protein is


Antibodies, contractile proteins, and enzymes are three important types of specialized proteins found in

ing in the cytoplasm, translation is the process through which proteins are synthesized.

from cellular support to cell signaling and cellular locomotion.

and some types of hormones, such as

While proteins have many diverse functions, all are typically constructed from one set of 20 amino acids.


s and they are linked by peptide bonds to form a protein or

), a carbon and a variable R

r chain of amino acids that make

is a bit more complex and refers to the arrangement or conformation of the amino acids.

helices are right handed, resemble

Certain types of amino acids are much more common

helices. Glycine can also be

internal.

β-sheets come in two

Parallel sheets occur when neighboring chains run in the same direction, and they

external, they alternate in β-

Parallel β-sheets are less

sheets.

Tertiary structure is the folding of secondary structures and is the 3D structure of the protein that we see in

pictures. The stabilization of this structure is more complex than the previous types. Hydrogen bonds,

hydrophobic interactions, ionic bonds, and disulfide bonds are involved in the stability of tertiary structures.

There are four types of tertiary structures. The most common is the β-α-β motif in which the α-helix connects two

β-sheets. Next is the β-hairpin, which is also common and consists of antiparallel β-sheets that are connected by

tight turns. The α-α motif is the most favourable and is formed by tightly packed α-helices. The final type is the

Greek key motif, which is created by the folding of β-hairpins to form four anti-parallel sheets.

Quaternary structures exist in proteins with multiple subunits and describe the folding and arrangement of these

subunits. An example of a protein that exhibits quaternary structure is haemoglobin. The structure of proteins is

vital, and can be maintained in a few different ways.

Function of Protein:

Proteins has a wide array of crucial functions in our bodies. They store amino acids, function as antibodies, act

as hormones, have structural functions, transport important molecules and last but certainly not least, proteins

can act as enzymes. There are many examples of each type, but everyone is familiar with at least a few of them.

Some of the most common include transport proteins, enzymes, hormones and structural proteins.

Haemoglobin and myoglobin are examples of transport proteins and are responsible for oxygen transport, while

pepsin is an enzyme that is essential for the digestion of food.

Hormones, such as insulin, are proteins that maintain essential bodily functions. Structural proteins help hold us

together. These include connective tissues such as keratin and collagen.

Examples of protein functions:

Function Description Example

Antibody Antibodies bind to specific foreign particles, such as viruses and

bacteria, to help protect the body.

Immunoglobulin G

(IgG)

Enzyme Enzymes carry out almost all of the thousands of chemical reactions

that take place in cells. They also assist with the formation of new

molecules by reading the genetic information stored in DNA.

Phenylalaninehydr-

oxylase

Messenger Messenger proteins, such as some types of hormones, transmit

signals to coordinate biological processes between different cells,

tissues, and organs.

Growthhormone

Structural

component

These proteins provide structure and support for cells. On a larger

scale, they also allow the body to move.

Actin

Transport/

storage

These proteins bind and carry atoms and small molecules within cells

and throughout the body.

Ferritin

What are proteins and what do they do?

Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells

and are required for the structure, function and regulation of tissues and organs of the body.

Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one

another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The

sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function.

Proteins can be described according to their large range of functions in the body, listed in alphabetical order:

Examples of protein functions

Function Description Example

Antibody Antibodies bind to specific foreign particles, such as viruses and bacteria,

to help protect the body.

Immunoglobulin G (IgG)

Enzyme Enzymes carry out almost all of the thousands of chemical reactions that

take place in cells. They also assist with the formation of new molecules

by reading the genetic information stored in DNA.

Phenylalaninehydroxylase

Messenger Messenger proteins, such as some types of hormones, transmit signals

to coordinate biological processes between different cells, tissues, and

organs.

Growthhormone

Structural

component

These proteins provide structure and support for cells. On a larger scale,

they also allow the body to move.

Actin

Transport/st

orage

These proteins bind and carry atoms and small molecules within cells

and throughout the body.

Ferritin

Nucleic Acids

Nucleic acids are the polynucleotides with high molecular weight.

that are linked in a chain through phosphodiester bonds.

are two types of nucleic acids: ribonucleic acid (RNA)

(i) Ribonucleic Acid (RNA):

RNA may be found in nucleus but mainly occurs in cytoplasm carry out protein synthesis work.

of RNA: transfer RNA (t-RNA), messenger RNA (m

(ii) Deoxyribonucleic acid (DNA)

DNA occurs in nucleus as well as cell organells like chloroplast and mitochondria.

Structure of Nucleic Acids:

Both DNA and RNA are long, un-branched polymers of

composed of three components covalently bound together. These components are:

base, sugar and phosphate group. The combination of a base and sugar is called as

nucleoside). These are bound through glycoside bond.

as nucleotide (Nucleoside + phosphoric acid = nucleotide)

(i) Nitrogenous Bases of DA and RNA:

Nitrogenous bases in nucleic acids are:

contain four different bases. Purines (6-

membered (imidazole ring) nitrogen-containing rings, fused together.

Pyridmidines (2-amino-6-oxy purine) have only a six

nitrogen atoms. Purines include: adenine (A)

and uracil (U). Adenine, guanine and cytosine are present in both

replaced by uracil in RNA.

These bases can interact through hydrogen bonds.

pyrimidine. The standard Watson-Crick base

stabilizes the native three-dimensional structures of DNA and RNA.

Adenine Guanine Cytosine

Purines Pyrimidines

are the polynucleotides with high molecular weight. Building blocks of all nucleic acids

phosphodiester bonds. Mainly they serve as information

ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).

eus but mainly occurs in cytoplasm carry out protein synthesis work.

essenger RNA (m-RNA) and ribosomal RNA (r-RNA).

(ii) Deoxyribonucleic acid (DNA):

occurs in nucleus as well as cell organells like chloroplast and mitochondria.

branched polymers of nucleotides. Each nucleotide units have a distinctive stru

composed of three components covalently bound together. These components are: nitrogen containing heterocyclic

The combination of a base and sugar is called as nucleoside

glycoside bond. The combination of a nucleoside and

(Nucleoside + phosphoric acid = nucleotide). These are bound through ester bond

Nitrogenous Bases of DA and RNA:

are: purines (two rings) and pyrimidines (one ring). Both

-amino purine) consist of a six-membered (pyrimidine ring

containing rings, fused together. They contain four nitrogen atoms.

oxy purine) have only a six-membered nitrogen-containing ring.

adenine (A) and guanine (G) and pyrimidines include: cytosine (C), thymine (T)

. Adenine, guanine and cytosine are present in both DNA and RNA. Thymine present in DNA is

These bases can interact through hydrogen bonds. Hydrogen-bonded pairs composed of one purine and one

base pairs are G-C and A-T in DNA and G-C and A

dimensional structures of DNA and RNA.

Guanine Cytosine Thymine

Purines Pyrimidines

nucleic acids are nucleotides

Mainly they serve as information-carrying molecules. There

eus but mainly occurs in cytoplasm carry out protein synthesis work. There are three types

units have a distinctive structure

nitrogen containing heterocyclic

nucleoside (base + sugar =

and phosphoric acid is called

ester bond.

(one ring). Both DNA and RNA

pyrimidine ring) and a five-

They contain four nitrogen atoms.

containing ring. They contain only two

cytosine (C), thymine (T)

Thymine present in DNA is

pairs composed of one purine and one

C and A-U in RNA. Base pairing

Uracil

Structure of Purine

Structure of Pyrimidine

(ii) Sugar:

Nucleic acids have five-carbon ribose or deoxyribose sugar. If the

sugar in a nucleotide is deoxyribose, the nucleotide is called a

deoxynucleotide whereas if the sugar is ribose (an extra hydroxyl

group on the 2' carbon), the term ribonucleotide is used.

(iii) Phosphate Group:

Nucleotides contain two or three

phosphates, called nucleotide

diphosphates or triphosphates.

All nucleic acids have two

distinctive ends: the 5' and 3'

carbons on the sugar (5-prime

and 3-prime ends). For both DNA

and RNA, the 5' end bears a

phosphate and the 3' end a

hydroxyl group. Nucleic acids

involve phosphodiester bonds

between the 3' carbon of one

nucleotide and the 5' carbon of

another nucleotide. This leads to

formation of sugar-phosphate

backbone, from which the bases

project. Another important

concept in nucleic acid structure

is that DNA and RNA polymerases

add nucleotides to the 3' end of

the previously incorporated base.

Most DNA exists in the form of a double helix, in which two linear strands of DNA are wound around one another.

The two strands of DNA are arranged anti-parallel to one another. Viewed from left to right the top strand is

aligned 5' to 3', while the bottom strand is aligned 3' to 5'.

This is always the case for duplex nucleic acids. G-C base pairs have 3 hydrogen bonds, whereas A-T base pairs

have 2 hydrogen bonds. One consequence of this disparity is that it takes more energy (e.g. a higher temperature)

to disrupt GC-rich DNA than AT-rich DNA. The structure is divided into four different levels, primary, secondary,

tertiary and quaternary.

Base Pairing and Double Stranded Nucleic Acids

Structure of DNA

Primary Structure:

Primary structure of nucleic acids is a linear

sequence of nucleotides, which are linked to each

other by phosphodiester linkages.

Secondary Structure:

Secondary structure is the interaction between

the bases. This structure shows parts of which

strands are bound to each other. The two

strands of DNA in the double helix of the DNA

are bound to each other by hydrogen bounds.

The nucleotides on one strand base pairs with

the nucleotides of the other strand. The

secondary structure of the DNA is

predominantly the base pairing of the two poly

nucleotide strands forming a double helix.

Tertiary Structure:

Tertiary structure is the three dimensional

shape into which the entire chain is folded.

Tertiary structure arrangement differs in four

structural forms:

Left or right handedness.

Length of the turn of the helix.

Number of base pairs per turn.

The difference in size between major and

the minor groove.

Quaternary Structure:

Quaternary structure is the higher-level

organization of the nucleic acids. This

structure refers to the interactions of the

nucleic acids with the other molecules. The

most commonly seen organization is the

form of chromatin which shows interaction

with small proteins histones.

is a linear

are linked to each

is the interaction between

re shows parts of which

strands are bound to each other. The two

strands of DNA in the double helix of the DNA

are bound to each other by hydrogen bounds.

The nucleotides on one strand base pairs with

the nucleotides of the other strand. The

cture of the DNA is

predominantly the base pairing of the two poly-

nucleotide strands forming a double helix.

Tertiary structure is the three dimensional

shape into which the entire chain is folded.

differs in four

The difference in size between major and

level of

organization of the nucleic acids. This

structure refers to the interactions of the

nucleic acids with the other molecules. The

most commonly seen organization is the

form of chromatin which shows interaction

Functions of Nucleic Acids:

Main functions of nucleic acids are:

To store and transfer genetic information.

To use the genetic information to direct the synthesis of new protein.

The deoxyribonucleic acid is the storage for place for genetic information in the cell.

DNA controls the synthesis of RNA in the cell.

The genetic information is transmitted from DNA to the protein synthesizers in the cell.

RNA also directs the production of new protein by transmitting genetic information to the protein building

structures.

The function of the nitrogenous base sequences in the DNA backbone determines the proteins being

synthesized.

The function of the double helix of the DNA is that no disorders occur in the genetic information if it is lost or

damaged.

RNA directs synthesis of proteins.

m-RNA takes genetic message from RNA.

t-RNA transfers activated amino acid, to the site of protein synthesis.

r-RNA are mostly present in the ribosomes, and responsible for stability of m-RNA.

Fatty Acids:

Fatty acids are the primary constituents of our cells inside and outside. We get fatty acids from foods and the

nutritional supplements. These are long-chain hydrocarbons containing a carboxylic acid moiety at one end. At

physiological pH, the carboxylic group is readily ionized, rendering a negative charge onto fatty acids in bodily

fluids. Two essential fatty acids, linoleic and alpha-linolenic acids cannot be synthesized in the body and must be

obtained from food. These basic fats, found in plant foods, are used to build specialized fats called omega-3 and

omega-6 fatty acids.

Fatty acids that contain no carbon-carbon double bonds are termed saturated fatty acids and those that contain

double bonds are unsaturated fatty acids. Fatty acids with multiple sites of unsaturation are termed

polyunsaturated fatty acids (PUFAs). The numeric designations used for fatty acids come from the number of

carbon atoms, followed by the number of sites of unsaturation (e.g., palmitic acid is a 16-carbon fatty acid with no

unsaturation and is designated by 16:0).

Palmitic acid

Fatty acids are released from triacylglycerols during fasting to provide a source of energy and to form the

structural components for cells. Dietary fatty acids of short and medium chain size are not esterified but are

oxidized rapidly in tissues as a source of fuel. Longer chain fatty acids are esterified first to triacylglycerols or

structural lipids. The majority of fatty acids found in the body are acquired in the diet. However, the lipid

biosynthetic capacity of the body (fatty acid synthase and other fatty acid modifying enzymes) can supply the body

with all the various fatty acid structures needed.

Biological Importance of Fatty Acids:

Fatty acids (FA) play multiple roles in humans and other organisms. First and most important, FA are a substantial

part of lipids, one of the three major components of biological matter (along with proteins and carbohydrates). FA

containing lipids form the back bone of all cell membranes. These are also important energy sources.

They can be stored practically in unlimited quantities as shown in obese humans. Unsaturated FA with 18-20

carbon atoms are precursors of prostaglandins, leucotrienes and thromboxanes, which have a broad scale of

regulatory properties and have autocrine as well as paracrine effects.

Fatty acids are ligands of several nuclear receptors, which take part in the sub-cellular control of a number of

metabolic pathways. Covalent modification of proteins by FA acylation enables FA incorporation into membranes.

Fatty acids with 20 and 22 carbon atoms are precursors of further autacoids—resolvins (resolution phase

interaction products), lipoxins and neuroprotectins. Hydroxy FA are activators of some nuclear factors (e.g. NFκB,

AP-1 and TNF-α) and are responsible for the expression of proinflammatory cytokines (e.g. IL-1, IL-6, IL-8 and TNF-

α) and adhesion molecules (e.g. ICAM-1, VCAM-1 and ELAM-

1). Fatty acids are either saturated or unsaturated carboxylic acids with carbon chain varying between 2 and 36

carbon atoms. In higher animals and plants FA with 16 and 18 carbon atoms, i.e. palmitic, stearic, oleic and linoleic

dominate. Fatty acids with chain length shorter than 14 and longer than 22 carbon atoms are present only in

minor concentrations. Most FA have an even number of carbon atoms, as they are synthesized from two-carbon

units. Approximately one half of FA in plants and animals are unsaturated and contain 1-6 double bonds.

Polyunsaturated FA (PUFA) are characterized by pentadiene configuration of double bonds. Fatty acids are often

expressed by the schematic formula CN:p n-x, where CN (carbon number) represents total number of carbon

atoms, p - number of double bonds, and x – position of the first double bond from the methyl group (n).

Essential fatty acids (linoleic acid and alpha-linolenic acid) are critical for human survival. These are readily

available in the diet, but to derive their full benefit, they need to be metabolized to their respective long-chain

metabolites. They serve as the cell's gatekeeper. Operating the sodium-potassium, pump that regulates the

opening and closing of the metabolic pathways. Through a chemical transformation, they become prostaglandins

that protect the body against unhealthy outside agents. Layers of subcutaneous fat under the skin also help in

insulation and protection from cold. Maintenance of body temperature is mainly done by brown fat as opposed to

white fat. Babies have a higher concentration of brown fat. FA have four important functions in the body:

(i) As Building Blocks:

Fatty acids are the building blocks of phospholipids, glycolipids, and lipoproteins that are found in the biological

membranes. They play the leading role in the construction and maintenance of all healthy cells, more importantly

the cell membrane. Essential fatty acids form arachidonic, eicosapentaenoic and docosahexaenoic acids. These

form membrane lipids that are made of polyunsaturated FA. Polyunsaturated fatty acids are important as

constituents of the phospholipids, where they appear to confer several important properties to the membranes.

One of the most important properties is fluidity and flexibility of the membrane.

(ii) As Targeting Molecules:

Fatty acids are attached to many proteins. In this way proteins are directed to their appropriate place in

membranes.

(iii) As Fuel Molecules:

Fatty acids are fuel molecules, stored as triglycerides (or neutral fats or triacylglycerols that are esters of glycerol

and fatty acids) in the fat-cells (adipose cells). Under the influence of hormone adrenaline adipose cells hydrolyze

the triglycerides into free fatty acids that are released into the blood. The complete oxidations of 3 fatty acids of a

triglyceride release 9 Kcal/g, in contrast to carbohydrate and protein that release 4 Kcal/g.

(iv) AS Messenger Molecules (Messengers):

Fatty acid derivatives act as hormones and intracellular messenger molecules (messengers). E.g. IP3 (inositol 1, 4,

5-triphosphate) and DAG (diacylglycerol).

(v) As Hormones:

Eicosanoids (prostaglandins, thromboxane’s and leukotriene’s) are the polyunsaturated fatty acids, which serve as

hormones.

(vi) Deficiency of EFA (essential fatty acids) in human diet causes sterility, kidney failure, skin lesions like

phrenoderma (hard skin), eczema etc.

(vii) Provide the insight to many diseases like obesity atherosclerosis etc.

(viii) Physicians recommend taking PUFA to those having high blood cholesterol or cardiovascular disease.

Metabolism of Fatty Acids:

Fatty acids are substantial components of lipids, which represent one of the three major components of biological

matter (along with proteins and carbohydrates). Chemically lipids are esters of fatty acids and organic alcohols—

cholesterol, glycerol and sphingosine. Pathophysiological roles of fatty acids are derived from those of individual

lipids. Fatty acids are synthesized adhoc in cytoplasm from two-carbon precursors, with the aid of acyl carrier

protein, NADPH and acetyl-CoA-carboxylase. Their degradation by β-oxidation in mitochondria is accompanied by

energy-release. Fatty acids in the mammalian organism reach chain

bonds. Their composition is species- as well as tissue

position, desaturation to another position is possible only from exogenous (essential) acids [linoleic (n

and α-linolenic (n-3 series)]. Circulating lipids (in form of lipoproteins) consist of cholesteryl esters and

triglycerides in nonpolar core and phosphatidylcholine and sphin

Non-esterified fatty acids (product of lipolysis and source for lipid synthesis) are bound to plasma albumin.

Membrane lipids, which ensure its fluidity and other functions, consist of phosphatidylcholine,

phosphatidylethanolamine, sphingomyeline and some other (minor) phospholipids. Unsaturated fatty acids with

18-20 carbon atoms are precursors of prostaglandins, leucotrienes and thromboxanes, which have a broad scale of

autocrine as well as paracrine effects. Fatty acids are ligands of several nuclear receptors, which take part in a

number of metabolic pathways. Covalent modification of proteins by acylation enables their incorporation into

membranes. A number of pathological conditions is accompanied with c

expressed as decreased content of unsaturated and increased content of saturated fatty acids (e.g. dyslipidemia,

malnutrition, inflammation and inherited diseases).

Lipids:

Lipids are bioorganic compounds found in plant and animal tissues. They contain carbon, hydrogen and oxygen

elements. All lipids are insoluble in water but soluble in non

Although humans and other mammals use various

lipids, some essential lipids cannot be made this way and must be obtained

these are poor in oxygen and therefore require more oxygen for oxidation to release energy.

Lipids comprise a group of naturally occurring

(such as vitamins A, D, E, and K), monoglycerides, diglycerides, triglycerides,

a much more diverse and widespread biological role in the body in terms of intracellular signalling or local

hormonal regulation etc.

release. Fatty acids in the mammalian organism reach chain-length 12-24 carbon atoms, with 0

as well as tissue-specific. Endogenous acids can be desaturated up to Δ9

position is possible only from exogenous (essential) acids [linoleic (n

3 series)]. Circulating lipids (in form of lipoproteins) consist of cholesteryl esters and

triglycerides in nonpolar core and phosphatidylcholine and sphingomyeline in the polar envelope of lipoproteins.

esterified fatty acids (product of lipolysis and source for lipid synthesis) are bound to plasma albumin.


hosphatidylethanolamine, sphingomyeline and some other (minor) phospholipids. Unsaturated fatty acids with

20 carbon atoms are precursors of prostaglandins, leucotrienes and thromboxanes, which have a broad scale of

s. Fatty acids are ligands of several nuclear receptors, which take part in a


membranes. A number of pathological conditions is accompanied with changes in fatty acid composition, often


malnutrition, inflammation and inherited diseases).


elements. All lipids are insoluble in water but soluble in non-polar solvents like ether, chloroform, benzene,

Although humans and other mammals use various biosynthetic pathways both to break down and to synthesize

lipids, some essential lipids cannot be made this way and must be obtained from the diet. Like carbohydrates


comprise a group of naturally occurring molecules that include fats, waxes, sterols

monoglycerides, diglycerides, triglycerides, phospholipids


Structures of some common lipids

24 carbon atoms, with 0- 6 double

specific. Endogenous acids can be desaturated up to Δ9

position is possible only from exogenous (essential) acids [linoleic (n-6 series)

3 series)]. Circulating lipids (in form of lipoproteins) consist of cholesteryl esters and

gomyeline in the polar envelope of lipoproteins.

esterified fatty acids (product of lipolysis and source for lipid synthesis) are bound to plasma albumin.


hosphatidylethanolamine, sphingomyeline and some other (minor) phospholipids. Unsaturated fatty acids with

20 carbon atoms are precursors of prostaglandins, leucotrienes and thromboxanes, which have a broad scale of

s. Fatty acids are ligands of several nuclear receptors, which take part in a


hanges in fatty acid composition, often



polar solvents like ether, chloroform, benzene, etc.

both to break down and to synthesize

from the diet. Like carbohydrates


sterols, fat-soluble vitamins

and others. They have


Lipids are synthesized in the body using complex biosynthetic pathways. However, there are some lipids that are

considered essential and need to be supplemented in diet. The lipids of physiological importance for humans exert

the following major functions:

� They serve as structural components of biological membranes.

� They provide energy reserves, predominantly in the form of triglycerides (TGs; also called triacyglycerols,

TAGs).

� Lipids and lipid derivatives serve as biologically active molecules exerting a wide range of functions.

� Lipophilic bile acids aid in emulsification, digestion and absorption of dietary lipids as well as being a form of

bioactive lipids.

Biological Importance of Lipids:

The biological importance of lipids is summarized as:

1. Storage: Lipids are non-polar and so are insoluble in water.

2. High-energy store: They have a high proportion of H atoms relative to O atoms and so yield more energy than

the same mass of carbohydrate.

3. Production of metabolic water: Some water is produced as a final result of respiration.

4. Thermal insulation: Fat conducts heat very slowly so having a layer under the skin keeps metabolic heat in.

5. Electrical insulation: The myelin sheath around axons prevents ion leakage.

6. Waterproofing: Waxy cuticles are useful, for example, to prevent excess evaporation from the surface of a leaf.

7. Hormone production: Steroid hormones. Oestrogen requires lipids for its formation, as do other substances

such as plant growth hormones.

8. Buoyancy: As lipids float on water, they can have a role in maintaining buoyancy in organisms.

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Heterocyclic and Bioorganic Chemistry Unit IV Bioorganic ... · Bioorganic chemistry is the area that includes metabolism, biosynthesis, transformation, ... molecules and materials