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Heterocyclic compounds
with biological meaning
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Heterocyclic compounds
Cyclic, organic compounds which despite carbon
atoms have one or more heteroatom of other
elements.
Heterocyclic atoms:
– Nitrogen, N
– Sulphur, S
– Oxygen, O
– Phosphor, P
– Barium, Ba
– Zinc, Zn
– Silica, Si
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Heterocyclic compounds
• Saturated heterocyclic compounds:
• Heterocyclic compounds with the following rings:
– 5- membered ring and 2 double bonds
– 6- membered ring with 3 double bonds
• Most of the heterocyclic compounds have common names
• Substituent’s position in ring is described by :
– numbers – position of heteroatom as a number 1
– Greek letters – describes carbon atom position which is
situated the closest to heteroatom as α, for further
respectively β and γ
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Heterocyclic compounds
Heterocyclic compounds are:
• Widely present in nature
• Biologically active
• Some are toxic (e.g. coniine, coumarin and derivatives)
Occurrence in:
• Natural dyes - hem, chlorophyl
• Alkaloids – atropine and nicotine
• Aminoacids such as tryptophan and histydyne
• Enzymes, nucleoproteins, antibiotics
• Vitamins
• Many synthetic pharmaceuticals
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Heterocyclic compounds
From medical stand point the highest importance have heterocyclic
compounds with:
• 5-membered ring
• 6-membered ring
• containing sulphur, nitrogen and oxygen
Aromatic character of heteroatom ring comes from aromatic
sextet which is consisting of:
• „not bounded” electron pairs of heteroatoms
• four electrons π from carbon atoms
Pyrol
Furane
Thiophen
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5- membered ring heterocyclic compounds with
one heteroatom
5-membered rings:
•are containing mostly oxygen, sulphur and nitrogen
•are flat
•are aromatic
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5- membered ring heterocyclic compounds with
two heteroatoms
oxazole
imidazole
thiazole
pyrazole
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5- membered ring heterocyclic compounds
With one heteroatom
With two heteroatoms
Condensation products with benzene
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Pyrrole and derivatives
• Pyrrole derivatives:
• Pyrroline
• Pyrrolidone
• Proline,
• Hydroksypyrroline,
• Condensation’s products of pyrrole with
benzene:
– Indole,
– Tryptophan,
– Serotonine
• Condensation’s products of pyrrole with
formaldehyde:
– Hem
– Hemoglobine
– Billirubin
– Porphyrins
– Biliverdina
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Pyrrole and derivatives. Porphyrins ring
Heme: cyclic tetrapyrrole containing iron
atom. Present as prostetic group of
hemoglobin, mioglobin, and citochromes
Terapyrols belong to dyes ”family”
Chlorophyles are cyclic tetrapyrrole containing
magnesium atom:
• photosynthesis center in plants
• dyes absorbing light
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Porphyrins ring: structure and metabolism
degradation
Bilirubin + albumin are transported to liver
where it combines with glucuronic acid and
therefore increases its solubility.
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5-membered ring with one heteroatom
5-hydroxytryptophane
serotonin
•Biologicaly activ amin
•Hormon which is also neuroconductor in central nerves system and in alimentary duct
•Necessary for sleep (animals with blocked serotonin production are sleepless)
coproduct transformed at night into melatonin (necessary for sleep)
Deficiency is causing apathy or agression, depression, increased
appatite for carbohydrates
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5-membered ring with two heteroatoms
decarboxylation
- CO2
histidine
histamine
Histidine
Structural element of electrolytic enzymes
Histamine (tissue hormone) :
present in plant and animal tissues
natural factor increasing permeability of veins leading to edema
(swelling)
is causing angiectasis (enlargement of a lymphatic or blood vessel.)
is causing decreasing of blood pressure
influences H2 receptors causing increased pulse and heart efficiency
acts as a stimuli of digestive secretion
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5-membered ring with two heteroatoms
Thiamine – Vitamin B1 - two rings system:
Pirimidyn and thiazo connected by methylene group
Thiamine pyrophosphate (cocarboxylases):
•coenzyme of pyruvate dehydrogenases (citiric acid cycle)
•Used in Beri-beri disease. Nerves infalmation caused by B1 deficiency.
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6-membered ring - heterocyclic
compounds
pyran
pyridine
pyrazine
pyrimydine
The most important derivatives of pyrane are monosaccharides:
•glucopyranose
•galactopyranose
•mannopyranose
Pyridine derivatives –biological active compounds:
• vitamin B6
• nicotine
• vitamin PP
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Vitamin PP –
nicotinic acid derivative
Nicotinic acid
nicotine
vitamin PP
Is part of:
• Redox processes in human body as a part of coenzymes
• Regulation process of sugar level in blood
• Regulation process of cholesterol level
• Regulation process of blood flow in veins
• Maintaining appropriate skin condition ( deficiency of vit. PP –
pellagra, from latin: pella agra – rough skin))
• Hormones synthesis (estrogen, progesterone)
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Vitamin B6 –
pyridoxine, pyridoxal phosphate
Pyridoxine
piridoxal
Pyridoxal phosphate
• Vitamin B6
– Water soluble
– Part of three natural pyridine compounds
– Is coenzyme for 50 different enzymes
• Is taking part of :
– protein transformation as a decarboxylases and transaminases
coenzyme in aminoacids transaminases
– transformation of tryptophane to serotonin
– protein and nucleic acid synthesis
Its necessary for hemoglobin synthesis
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Pyrimidine bases and their derivatives
Pyrimidyne:
1,3- diazyne – aromatic heterocyclic compound
containing two atoms of nitrates at position 1 and 3
Derivatives:
cytosine
uracyl
thymine
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Pyrimidine bases and derivatives
Keto-enol tautomrism:
Result of hydrogen transport,
Is causing that pirimidine bases are
present in the following forms:
• Lactam, keto structure (=O)
• Lactim, enol structure (-OH)
cytozine
uracyl
thymine
In physiological conditions dominant quantitatively tautomeric form:
• in thymine and uracyl - lactam
• in citozyne - lactim
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Condensed rings with heteroatoms
Riboflavin - vitamin B2
rybitol
• mononucleotide consisting of :
– Nitrate base called isoalloksazin
(polycyclic heterocyclic compound )
– ribitol, esterified by ortophosphorane
B2 participate in:
oxy/reduction proceses, normal functioning
isoalloksazin
in nerve system, eyes, mucous membranes,
respiratory system, aminoacids and lipids
transformation
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Purine base and their derivatives
Purine have pyrimidine ring
combined with imidazol ring.
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Purine bases and derivatives
Purines contain pyrimidine ring
combined with imidazol ring
In nature purine does not exist in free
form but as amino and keto derivatives
Amino groups attached to aromatic ring of purine
act similar to amine group from aminoacids, i.e. can
transform into cationic form after H+ addition.
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Purine bases and derivatives
Teophilin
(1,3-dimethyloxanthine)
Caffeine
Theobromine
(1,3,7-trimethylxanthine) (3,7-dimethylxanthine)
• Methylated purines are present in plants as plant’s bases
(alcaloids)
• Caffeine is present in coffee beans
• Teophilin is present in tea leaves
• Theobromine is present in cocoa fruits
• All have pharmacological application
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Purine bases and derivatives
Adenine
Guanine
Hipoxanthine
In physiological conditions main tautomeric forms are:
•for guanine and hipoxanthine - lactam
•for adenine - lactim
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Urea acid
xanthin
urea acid
Easily undergos keto-enol transformations
Mammals have urea acid in small quantities in blood, liver, spleen
and urea
In humans urea acid is a final product of purine bases metabolism
About 75% is removed with urea and 25% goes to digestion tract
and is decomposed by testiness bacteria
Not well soluble in water and therefore has a tendency to
accumulate in kidney (uric stones) and in joints
In base environment creates easily soluble urates
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Rings condensed with heteroatoms
Vitamin H
• Participate in:
– proteins and fats metabolism
– fatty acids synthesis
– vitamin C absorption
– aminoacids and sugars metabolism
– with vit. K in protein protrombin synthesis
is responsible for blood coagulation
• Resistant to heating, acids and bases
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Structure of nucleosides
Nucleosides are glycosides, riboside or deoxyribosides of purin
or pyrimidin bases.
Names depends on the type of purine or pyrimidyne bases.
Remove the phosphate group, and you have a nucleoside.
H
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Structure of nucleotides
Nucleotides have three characteristic components:
A nitrogenous base
A phosphate group
(pyrimidines or purine)
A, G,T,C,U
A pentose sugar
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Nucleotides and nucleic acids
Nucleotides are the building blocks of nucleic acids
Nucleotide
RNA
DNA
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Roles of nucleotides
• Building blocks of nucleic acids (RNA, DNA)
•Analogous to amino acid role in proteins
• Energy unit in cellular metabolism (ATP:
adenosine triphosphate)
• Allosteric effectors
• Structural components of many enzyme cofactors
(NAD: nicotinamide adenine dinucleotide)
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Nucleic acids are biopolymers with molecular weight about 106
daltons
RNA - contains ribonucleic acids (D-ribose)
DNA – contains deoxyribonucleic acid ( D-2-deoxyribose)
DNA contains adenine, guanine, cytosine , thymine
RNA contains adenine, guanine, cytosine, and uracil
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Nucleotide nomenclature
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DNA structure
• DNA consists of two helical
chains wound around the
same axis in a right-handed
fashion aligned in an
antiparallel fashion.
• There are 10.5 base pairs, or
36 Å, per turn of the helix.
• Alternating deoxyribose and
phosphate groups on the
backbone form the outside of
the helix.
• The planar purine and
pyrimidine bases of both
strands are stacked inside the
helix.
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DNA structure
• The furanose ring usually is
puckered in a C-2' endo
conformation in DNA.
• The offset of the relationship of
the base pairs to the strands
gives a major and a minor
groove.
• In B-form DNA (most common)
the depths of the major and
minor grooves are similar to
each other.
Pucker - To gather into small wrinkles or folds
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DNA strands
• The antiparallel strands of DNA are
not identical, but are complementary.
• They are positioned to align
complementary base pairs: C with G,
and A with T.
• The sequence of one strand given the
sequence of its complement can be
predicted.
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THE END
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