Download Nucleic acids

Classification, structure and biological role
of heterocyclic compounds and
of nucleic acids
Lecturer: Bekus Iryna

Heterocyclic compounds are cyclic
compounds in which one or more ring atoms
are not carbon (that is hetero atoms).

As hetero atom can be N, О, S, В, Al, Si, P, Sn,
As, Cu. But common is N, О, or S.
Classification

Heterocycles are
conveniently
grouped into two
classes,
nonaromatic:
and
aromatic

By size of ring
Three-membered
Four-membered
Five-membered
Six-membered
Tetrapyrrole compounds
blood heme
Five - membered heterocyclic compounds with one
heteroatom.
The structures of these three heterocyclic would suggest that they
have highly reactive diene character.
These heterocyclic have characteristics associated with aromaticity.
From an orbital point of view, pyrrole has a planar pentagonal structure
in which the four carbons and the nitrogen have sp² hybridization. Each
ring atom forms two sp²—sp²  bonds to its neighboring ring atoms,
and each forms one sp² – s  bond to a hydrogen.
Methods of synthesis of five - membered heterocyclec
compounds with one heteroatom.
1. Cyclization of 1,4-dicarbones compounds
H 2C
R
H
C
CH2
C
C
R
R
H2SO 4 c.
O O
C
H
C
C
R
OH HO
P 2S 5
NH3
R
O
R
R
R
N
H
R
S
R
Formation of furan:
In laboratory conditions furan is produced by dry distillation
of mucic acid.
OH
OH
CH
CH
CH
CH
CO
OH OH
OH
t
COOH
t
- 3 H2O
O
COOH
O
furan
furoic acid
dehydromucic acid
mucic acid
- CO2
- CO2
COOH
COOH O
t
In the industry furan derived from aldopentozes
H
H
HO
nH2O
(C5H8O4)n
t0
polypentoze
H
nC5H10O5
pentoza
H
- CO2
O
furoic acid
COOH
C
O
furan
H
C
C
t
O
C
OH
OH HO
C
t0
C
O
H
O
furfural
O
H
+ 3H2O
Formation of thiophene
Thiophene is prepared industrially by passing а
mixture of butane, butene, or butadiene and
sulfur through a reactor heated at 600' for а
contact time of about 1 sec
n- C4H10 + S
=
+ H2 S
Physical properties of furan, pyrrole, thiophene
At room temperature, thiophene is a colorless liquid with
a mildly pleasant odor reminiscent of benzene, with which
thiophene shares some similarities. Like benzene,
thiophene forms an azeotrope with water.
Furan is typically derived by the thermal decomposition
of pentose-containing materials, cellulosic solids
especially pine-wood. Furan is a colorless, flammable,
highly volatile liquid with a boiling point close to room
temperature. It is toxic and may be carcinogenic.
Pyrrole is a heterocyclic aromatic organic compound.
Substituted derivatives are also called pyrroles.
Porphobilinogen is a trisubstituted pyrrole, which is the
biosynthetic precursor to many natural products
Chemical properties of furan, pyrrole, thiophene
The typical reaction of furan, pyrrole, and
thiophene is electrophilic substitution. All three
heterocycles are much more reactive than benzene.
The reactivity order being is:
To give some idea of the magnitude of this reactivity order, partial rate
factors (reactivities relative to benzene) for tritium exchange with
fluoroacetic acid.
Reciprocal transformation of furan, pyrrole, thiophene
(Yurie`s cycle reactions)
пірол
H2S
Furan
H2O
Thiophene
1. Interaction with dilute mineral acids
Pyrroles are polymerized by even dilute acids, probably by a mechanism
such as the following .
2. Reactions of electrophilic substitution:
This orientation is understandable in terms of the mechanism of
electrophilic aromatic substitution. The / ratio is determined
by the relative energies of the transition states leading to the
two isomers. As in the case of substituted benzenes, we may
estimate the relative energies of these two transition states by
considering the actual reaction intermediates produced by
attack at the -or -positions.
a)
Nitration
(CH3CO)2O + р.HNO3
N
N
H
H
NO2
2-nitropyrrole
Sulfonation
+
X
X=O, NH
+
N
SO3
pyridine
sulfotrioxide
X
SO3H
furan-2-sulfoacid
pyrrole-2-sulfoacid
N
pyridine
Acylation
(CH3CO)2O
N
H
SnCl4
N
H
C
CH3
O
2-acetylpyrrole
Because of this high reactivity, even mild electrophiles to
cause reaction. Substitution occurs predominantly at the αposition (С-2).
Of these structures, the most important are the two with the positive charge on
sulfur because, in these two sulfonium cation structures, all atoms have octets of
electrons. Nevertheless, as the sets of resonance structures show, the charge on the
cation resulting from attack at the -position is more extensively delocalized than
that for the cation resulting from attack at the -position. The following examples
further demonstrate the generality of -attack.
Halogenation
In the last example, note that 2-iodothiophene is the sole
product of iodination, eyeu though the reaction is carried out
in benzene as solvent; that is, thiophene is so much more
reactive than benzene that no significant amount of
iodobenzene is formed.
Reactions of reconstruction
Thiophen are more stable and do not undergo hydrolysis.
Reduction of pyrrole:
Ni
+
2 H2
O
O
tetrahydrofuran
furan
Pd
+
S
thiophene
2 H2
S
tetrahydrothiophene
Reactions of oxidation
O
O
V2O5
O
O
O
maleinic anhydride
furan
O
NH
pyrrole
H2Cr2O4 O
NH
O
maleinmide
For identification of pyrrole and furan used
the method coloring of a pine chip.
Couples of pyrrole painted a pine chip
soaked in hydrochloric acid in the red
colour and furan - in the green colour.
Qualitative reaction on thiophene is
indophenin`s reaction: a mixture of
izathine with concentrated sulfuric acid
painted in the blue colour.
The important derivatives of pyrrole, furan and
thiophene.
The important derivatives of pyrrole, furan and
thiophene.
thiophene
tetrahidrothiofene
biotin
Five-membered heterocyclec with
two heteroatoms
pyrazole
Imidazole
thiazole
Six-membered heterocyclic compounds
pyridine group
Pyridine
quinoline
nicotinic acid
nicotinamide
Six-membered heterocycles with two
heteroatoms
pyrazine
pyrimidine
pirydazine
Characteristic for pyridine reactions can be
divided into three groups:
1)
Reactions which followings with participation of
heteroatom.
2) Reactions of substituting for the hydrogen atoms of
pyridines ring.
3) Reactions of reduction and oxidization.
Reactions which followings with participation of heteroatom.
1. Cooperating with acids.
Due to the indivisible pair of electrons atom of nitrogen of
pyridine shows weak basic properties. At cooperating with strong
mineral and organic acids he forms soluble salt of pyridine.
pyridine bromide
2. Reaction with the oxide of sulphur (VI).
Reactions of reduction and oxidization.
1.
Reduction .
pyperedine
2. Oxidization .
nicotinic acid
Reactions of substituting for the hydrogen atoms of pyridines
ring.
1. Reactions of electrophilic substitution (SE).
The reactions of nitration, sulphonation and halogenation pass
slowly drastic and with low exits. Thus an electrophilic reagent is
direct in position 3.
3-nithropyridine
3-pyridinesulphure acid

These ring systems, particularly that of pyrimidine, occur
commonly in natural products.
The pyrimidines, cytosine, thymine, and uracil are especially
important because they are components of nucleic acids, as
are the purine derivatives adenine and guanine.
Nucleic acids
A Nucleic acids are polymers of nucleotides joined by 3',5' phosphodiester bonds; that is, a phosphate group links the 3' carbon
of a sugar to the 5' carbon of the next sugar in the chain. A
phosphate group is often found at the 5' end, and a hydroxyl group
is often found at the 3' end.
Types of nucleic acids.
Two types of nucleic acids are found within cells of
higher organisms: deoxyribonucleic acid (DNA)
and ribonucleic acid (RNA). Nearly all the DNA is
found within the cell nucleus. Its primary function
is the storage and transfer of genetic information.
This information is used (indirectly) to control
many functions of a living cell. In addition, DNA is
passed from existing cell to new cells during cell
division RNA occurs in all parts of a cell. It
functions primarily in synthesis of proteins, the
molecules that carry out essential cellular
functions.
The monomers for nucleic acid polymers,
nucleotides, have а more complex structure
than
polysaccharide
monomers
(monosacharides) or protein monomers (amino
acids). Within each nucleotide monomer are
three subunits. А nucleotide is, а molecule
composed of a pentose sugar bonded to both a
group and a nitrogen-containing hetero-cyclic
base.
• Pentose sugars.
• The sugar unit of а nucleotide is either the
pentose ribose or the 2-deoxyribose.
Nitrogen-containing bases.

Five nitrogen-containing bases are nucleotide
components. Three of them are derivatives of
pyrimidine, а monocyclic base with а six-membered
ring, and two are derivatives of purine, а bicyclic base
with fused five- and six-membered rings.
Nucleosides
are compounds formed when a base is
linked to a sugar via a glycosidic bond.
Cytidine
Uridine
Thymidine
Nucleotide

A nucleotide results when phosphoric acid
is esterified to a sugar OOH group of a
nucleoside. The nucleoside ribose ring has
three OOH groups available for
esterification, at C-2, C-3, and C-5
(although 2-deoxyribose has only two). The
vast majority of monomeric nucleotides in
the cell are ribonucleotides having 5phosphate groups.
Nucleotide formation.

The formation of а nucleotide from sugar,
base, and phosphate can be visualized as
occurring in the following manner:
Nucleotide nomenclature.
There are two major classes of nucleic acids –
DNA and RNA.
DNA has only one biological role, but it is the more central one.
The information to make all the functional macromolecules of
the cell (even DNA itself) is preserved in DNA and accessed
through transcription of the information into RNA copies.
Coincident with its singular purpose, there is only a single DNA
molecule (or “chromosome”) in simple life forms such as
viruses or bacteria. Such DNA molecules must be quite large in
order to embrace enough information for making the
macromolecules necessary to maintain a living cell RNA has a
number of important biological functions, and on this basis,
RNA molecules are categorized into several major types:
messenger RNA, ribosomal RNA, and transfer RNA.
Eukaryotic cells contain an additional type, small nuclear RNA
(snRNA).
DNA
The DNA isolated from different
cells and viruses characteristically
consists of two polynucleotide
strands wound together to form a
long, slender, helical molecule, the
DNA double helix. The strands
run in opposite directions; that is,
they are antiparallel and are held
together in the double helical
structure through interchain
hydrogen bonds


DNA molecules are the carriers of the genetic information
within а cell; that is, they the molecules of heredity. Each
time а cell divides, an exact copy of the DNA of the present
cell is needed for the new daughter cell. The process by
which new DNA molecule generated is DNA replication
DNA replication is the process by which DNA molecules
produce exact duplicates of themselves. The key concept
in understanding DNA replication is the base pairing
associated with the DNA double helix.
We can divide the overall process of protein synthesis into
two steps. The first step is called transcription and the
second translation. Transcription is the process by which
DNA directs the synthesis of RNA molecules that carry the
coded information needed for protein synthesis.
Translation is the process by which the codes within RNA
molecules are deciphered and а particular protein molecule
is formed. The following diagram summarizes the
relationship between transcription and translation.
DNA to RNA Transcription
The DNA contains the master plan for the creation of
the proteins and other molecules and systems of the
cell, but the carrying out of the plan involves transfer
of the relevant information to RNA in a process
called transcription. The RNA to which the
information is transcribed is messenger RNA
(mRNA).
Ribonucleic acids (RNA).
Four major differences exist between RNA molecules and
DNA molecules.
1. The sugar unit in the backbone of RNA is ribose; it is
deoxyribose in DNA.
2. The base thymine found in DNA is replaced by uracil in
RNA. Uracil, instead of thymine, pairs with (forms
hydrogen bonds with) adenine in RNA.
3. RNA is а single-stranded molecule; DNA is doublestranded (double helix). Thus RNA, unlike DNA, does
not contain equal amounts of specific bases.
4. RNA molecules are much smaller than DNA molecules,
ranging from as few as 75 nucleotides to а few
thousand nucleotides.
Differences exist between RNA molecules
and DNA molecules.
Types of RNA
Thank you for attention