Pharmaceutical Chemistry last part according to UG CBPBU Syllabus

1. Pharmaceutical Chemistry
Dr. Santanu Chakravorty
Assistant Professor
Mathabhanga College
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2. Syllabus of CBPBU for 4th SEM
Drugs & Pharmaceuticals
Drug discovery, design and development; Basic Retrosynthetic approach.
Synthesis of the representative drugs of the following classes: analgesics
agents, antipyretic agents, anti-inflammatory agents (Aspirin,
paracetamol, lbuprofen); antibiotics (Chloramphenicol); antibacterial and
antifungal agents (Sulphonamides; Sulphanethoxazol, Sulphacetamide,
Trimethoprim); antiviral agents (Acyclovir), Central Nervous System agents
(Phenobarbital, Diazepam),Cardiovascular (Glyceryl trinitrate), antilaprosy
(Dapsone), HIV-AIDS related drugs (AZT- Zidovudine).
Fermentation
Aerobic and anaerobic fermentation. Production of (i) Ethyl alcohol and citric acid,
(ii) Antibiotics; Penicillin, Cephalosporin, Chloromycetin and Streptomycin, (iii)
Lysine, Glutamic acid, Vitamin B2, Vitamin B12 and Vitamin C.
I will discuss Fermentation portions only in this slide show
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3. Fermentation
Fermentation is a metabolic process that produces chemical changes in
organic substrates through the action of enzymes. In biochemistry, it is narrowly
defined as the extraction of energy from carbohydrates in the absence
of oxygen. In food production, it may more broadly refer to any process in which
the activity of microorganism brings about a desirable change to a foodstuff or
beverage. The science of fermentation is known as zymology.
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4. Aerobic and anaerobic fermentation
Aerobic and anaerobic fermentation are two types of cellular respiration involved
in the production of energy from glucose. Aerobic fermentation requires oxygen
while anaerobic fermentation does not require oxygen.
Aerobic fermentation or aerobic glycolysis is a metabolic process by which cells
metabolize sugars via fermentation in the presence of oxygen and occurs through
the repression of normal respiratory metabolism. It is referred to as the Crabtree
effect in yeast
Fermentation is an anaerobic pathway- a common pathway in the majority of
prokaryotes and unicellular eukaryotes. In this process, glucose is partially
oxidised to form acids and alcohol. In organisms like yeast, the pyruvic acid formed
by partial oxidation of glucose is converted to ethanol and carbon dioxide (CO2).
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5. Production of ethanol through fermentation
Ethanol fermentation, also called alcoholic fermentation, is a biological
process which converts sugars such as glucose, fructose, and sucrose into cellular
energy, producing ethanol and carbon dioxide as by-products.
Because yeasts perform this conversion in the absence of oxygen,
alcoholic fermentation is considered an anarobic process. It also takes place in
some species of fish (including goldfish and carp) where (along with lactic acid
fermentation) it provides energy when oxygen is scarce
(1) A glucose molecule is broken down via
glycolysis, yielding two pyruvate molecules.
The energy released by these exothermic
reactions is used to phosphorylate two ADP
molecules, yielding two ATP molecules, and
to reduce two molecules of NAD+ to NADH.
(2) The two pyruvate molecules are broken
down, yielding two acetaldehyde molecules
and giving off two molecules of carbon
dioxide. (3) The two molecules of NADH
reduce the two acetaldehyde molecules to
two molecules of ethanol; this converts
NADH back into NAD+
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6. Production of lactic acid through
fermentation
Lactic acid fermentation is a metabolic process by which glucose or other six
carbon sugars (also, disaccharide of six-carbon sugars, e.g. sucrose or lactose) are
converted into cellular energy and the metabolite lactate, which is lactic acid in
solution. It is an anaerobic fermentation reaction that occurs in some bacteria
and animal cells, such as muscle cells
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7. Vitamins
Vitamins are the constituents of the diet other than carbohydrates, fats, proteins,
and inorganic salts and are necessary for the normal metabolic functioning of the
body.
Vitamins are arbitrarily grouped according to the solubility in fats and water. The
water soluble vitamins are stored in the body only to a limited extent, whereas the
fat soluble vitamins are stored in significant quantity and body is able to conserve
these factors. The fat soluble vitamins are A and D and water soluble vitamins are
B, C and K
Vitamin-C founds in fruits and vegetable and is used for preventing scurvy. It has
a five-membered ring containing two carbonyl groups but normally exists as a
very conjugated ene-diol
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8. Vitamin-C synthesis
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9. Vitamin B12
Vitamin B12, also called cobalamin, is a water soluble vitamin that has key role in the normal
functioning of the brain and nervous system via the synthesis of myelin, and the formation of
red blood cells. It is involved in the metabolism of every cell of the human body, especially
affecting DNA synthesis, fatty acid and amino acid metabolism
Sources: No fungi, plants or animal are capable of producing vitamin B12, only Bacteria and
archaea have the enzymes needed for its synthesis. Some sources of B12 include animal
products and dietary supplement.
Structure: B12 is the most chemically complex of all the vitamins. The structure of B12 is
used on a corrin rig, which is similar to the porphyrin ring found in hem, chlorophyll and
cytochrome. The central metal ion is cobalt. Four of the six coordination sites are provided
by the corrin ring and a fifth by diemthylbenimidzole group. The six coordination site, the
center of reactivity is variable, being a cyano (CN), a hydroxy (-OH) and a methyl group (-
CH3) or a 5-deoxyadenosyl group, respectively, to yield the four B12 forms.
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10. Vitamin-B2
Sources: Riboflavin, also known as vitamin B2 is a vitamin found in food and used
as dietary supplement. Food sources include egg, green vegetables, milk and other
diary product, meat mushroom and almonds
Deficiency: The signs and symptoms of riboflavin deficiency (also known as
ariboflavinosis) include skin disorders, hyperemia (excess blood) and edema of the
mouth and throat, angular stomatitis (lesions at the corners of the mouth),
cheilosis (swollen, cracked lips), hair loss, reproductive problems, sore throat
Structure:
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11. Lysine
Lysine is an α-amino acid that is used in the biosynthesis of proteins. The human
body cannot synthesize lysine, so it is essential in humans and must be obtained
from the diet
Lysine plays several roles in humans, most importantly proteinogenesis, but also in
the cross-linking of collagen polypeptides, uptake of essential mineral-nutrients,
and in the production of carnitine, which is key in fatty acid metabolism
Due to its importance in several biological process, a lack of lysine can lead to
several disease states including defective connective tissues, anemia, and
systemic protein-energy deficiency
In contrast an overabundance of lysine can cause severe neurological issue
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12. Biosynthesis of Lysine
Two pathways have been identified in nature for the synthesis of lysine. The
diaminopimelate (DAP) pathway belongs to the aspertate derived biosynthetic family,
which's also involved in the synthesis of threonine, methionine and isoleucine. Whereas
the α-amino dipate (AAA) pathway is part of the glutamate biosynthetic family.
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13. Antibiotics from natural sources
Penicillins are a group of antibacterial drugs that attack a wide range of bacteria.
They were the first drugs of this type that doctors used. The discovery and
manufacture of penicillins have changed the face of medicine, as these drugs have
saved millions of lives.
The basic structure of the penicillins consists of a thiazolidine moiety fused with a
β-lactam ring,. The position are numbered as shown. There is side chain at
position 6. The character of the R group is influenced by the components of the
culture medium. The addition of phenyl acetic acid, for example, led to the
preferential formation of penicillin G. The natural penicilline produces by
penicillium notatum are listed here. Benzylpenicillin has the greatest antimicrobial
activity and is the only natural penicilin which is used clinically.
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14. Properties of Penicillin's
Penicillins are strong monobasic acids. The free acids are unstable. The alkali metal salts
and salts with organic acids are relatively stable in the dry state
In general following absorption, penicillins are widely distributed throughout the
body. They are eliminated rapidly by glomerular filtration and renal tubular
secretion. The half-lives in the body are short, the typical values are 30 to 60
minutes
Benzylpenicillin can be considered to be to be the parent compound of the
penicillin family. It is active gram-positive bacteria, gram-negative cocci,
actinomycetes and spirochates. It is usually injected since it is unstable to the
gastric acid.
Penoxymeththyl penicillin is acid stable and as such can be given by mouth. It is
generally used for relatively less severe infections. It is generally used for
relatively less sever infections and in rheumatic-fever prophylaxes.
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15. Cephalosporin's
The discovery of cephalosporin's may be traced to the year 1995 when G Brotzen
cultivated cephalosporium acremonium from sea water near a sewage outlet on
the coast of sardinia. He found that crude filtrates from cultures of this fungus
possessed therapeutic activity against staphylococcal infections and typhoid fever.
This aroused great interest and subsequent studies by different worker showed
that the cephalosporium produced seven different antibiotics which were termed
as cephalosporins
Five of the antibiotics were lipid soluble and one of them was shown to be
steroidal. The other two were hydrophilic and were designated as cephalosporin N
and cephalosporin C.
Cephalosporin's was found to be a β-lactam but it had structural differences as
compared with penicillin's. The lactam moiety was fused to 1,3-dihydrothiazine
ring instead of thiazolidine system. The thiazine ring fusion makes the β-lactam
system more stable but not fully resistant to opening by acids and penicillin's
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16. Structure and properties of Cephalosporin's
The first generation cephalosporin's have good activity against gram –positive
bacteria and they have relatively modest activity against gram negative bacteria
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17. Structure and properties of Cephalosporin's
The second generation cephalosporin's are slightly less active against gram-positive
bacteria but are more stable to hydrolysis by beta-lactamases produced by gram-
negetive bacteria and have enhanced activity against many of the
Enterobacteriaceae and Haemophilus influenza.
The third-generation cephalosporin's are even more resistant to hydrolysis by
beta-lactamases than the second generation drugs. They have wider-spectrum of
activity and are more active against gram negative organism.
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18. Streptomycin's
Streptomycin was the first aminoglycoside antibiotic to become commercially
available for chemotherapeutic use. It was isolated from strain of streptomyces
griseus. This proved to be the first clinically effective drug for the treatment of
tuberculosis.
Streptomycin is a triacidic base and it possesses an aldehydic carbonyl group. The
three structural units of the aminoglycoside are streptidire, streptose and N-
methyl-L glucosamine, connected through glycosidic linkage
Streptomycin's Streptidine Streptamine
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19. THANKS
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