VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTURES AND CHEMISTRY OF VITAMIN B1, HYSTORY OF VITAMIN B1, SOURCES OF VITAMIN B1, RDA, PHYSIOLOGICAL IMPORTANCE(ROLE) OF VITAMIN B1, SYNTHESIS OF VITAMIN B1, OXIDATION OF THIAMINE T
Vitamin B1, also known as thiamine, is a water-soluble vitamin that plays several critical roles in the body. It is required for the conversion of carbohydrates into glucose and for energy production. A deficiency can cause beriberi disease and related neurological issues. Vitamin B1 cannot be stored in the body and must be replenished daily through foods like pork, legumes, nuts and grains.
Similar to VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTURES AND CHEMISTRY OF VITAMIN B1, HYSTORY OF VITAMIN B1, SOURCES OF VITAMIN B1, RDA, PHYSIOLOGICAL IMPORTANCE(ROLE) OF VITAMIN B1, SYNTHESIS OF VITAMIN B1, OXIDATION OF THIAMINE T
Similar to VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTURES AND CHEMISTRY OF VITAMIN B1, HYSTORY OF VITAMIN B1, SOURCES OF VITAMIN B1, RDA, PHYSIOLOGICAL IMPORTANCE(ROLE) OF VITAMIN B1, SYNTHESIS OF VITAMIN B1, OXIDATION OF THIAMINE T (20)
VITAMIN B1 [THIAMINE] MEDICINAL CHEMISTRY BY P. RAVISANKAR [ SOURCE, STRUCTURES AND CHEMISTRY OF VITAMIN B1, HYSTORY OF VITAMIN B1, SOURCES OF VITAMIN B1, RDA, PHYSIOLOGICAL IMPORTANCE(ROLE) OF VITAMIN B1, SYNTHESIS OF VITAMIN B1, OXIDATION OF THIAMINE T
1. WATER SOLUBLE VITAMINS
The common features to most of vitamin B complex have been outlined below:-
•Cannot be stored in body - regular supply needed.
•most play an essential role in metabolism.
•Most of them can be sourced from liver and yeast.
•Most of them are synthesized by colonal bactera.
•Excess is excreted in urine(easily to be discharged through urine) - no
danger of toxic levels.
•not easy to be stored in the body,requiring diet inception.
•Unstable to heat and light, leach into cooking liquids.
•Classification
Vitamin B family
Vitamin B1 (thiamine), Vitamin B2 (riboflavin).
Vitamin B3 (niacin or niacinamide, sometimes also known as vitamin PP).
Vitamin B5 (pantothenic acid).
Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride).
Vitamin B7 (biotin), Vitamin B8 (inositol),Vitamin B9 (folic acid).
Vitamin B12 (various cobalamins; commonly cyanocobalamin in vitamin
supplements).
Prof. Ravisankar
Vignan Pharmacy coll
Valdlamudi
Guntur Dist.
Andhra Pradesh
India.
banuman35@gmail.co
00919059994000
Vitamin B1(Thiamine) (aneurin)
2. The B vitamins(water soluble vitamins) may be necessary in order to:
• Support and increase the rate of metabolism.
• Maintain healthy skin and muscle tone.
• Enhance immune and nervous system function.
• Promote cell growth and division, including that of the red blood cells that help
prevent anemia.
• Reduce the risk of pancreatic cancer.
• Vitamin B1 is needed to help convert the carbohydrates we eat into glucose
• The Vitamin B Complex is essential for the healthy functioning of the nervous system
• The Vitamin B Complex is essential for correct digestion, production of HCl (Hydrochloric
acid) and to assist in the breakdown of fats, proteins and carbohydrates.
• Healthy Skin, Hair and Nails
• The Vitamin B Complex is essential for correct RNA and DNA synthesis and cell
reproduction. Deficiencies of any of these B Vitamins can lead to dry,
grey skin, dermatitis, wrinkles, acne, rashes, falling hair and weak,
splitting nails.
• Thiamin is a water-soluble B-complex vitamin. It was the first B
vitamin to be identified and one of the first organic compounds to be
recognised as a vitamin in the 1930s. In fact it was through the
discovery and naming of thiamin that the word 'vitamin', from the
Latin “vita” = life and “amine” = nitrogen-containing
compound, was coined.
3. Vitamin B1
(thiamine )
Vitamin B1; antiberi-beri vitamin; antineuritic factor
was the first water soluble vitamin discovered (Eijkman)
﹡vitamin B1: thiamine
﹡active form :Thiamine pyrophosphate
(TPP):
Thiamine is one member of water-soluble vitamin B-complex
and is in the thermolabile fraction.
In the absence of thiamine which is the cause of beriberi
in man.
Thus this vitamin is the antineuritic factor (hence the name
aneurin)
Rice polishings and yeast have been the usual sources of thiamine.
4. • Structure and chemistry of vitamin B1(Thiamine)
• Thiamine consists of a thiazole and pyrimidine ring that are linked through a
methylene group.
• Thiamine is the only natural compound (apart from penicillin) that contains a
thiazole ring.
11
21
31
41
51
61
1
2
3 4
5
Pyrimidine
Thiazole
Methylene bridge(linkage)
(Vitamin B1)
C
H
Dissociable proton
Reactive carbon atom
3-[(4-amino-2methyl pyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)-4-methyl thiazolium.
Physico-Chemical Properties:
Thiamine is white,crystalline powder and slight,characteristic yeast-like odour.
It is freely soluble in water and slightly soluble in CHCl3 and ether.
It is stable in acid but unstable in aqueous solutions (pH >5) due to
5. • Christiaan Eijkman had decided he wanted to become a doctor. When the time
came, his family couldn't afford to send him to medical school.
• The Dutch colonial ( Indonesia was a Dutch colony) army had use for many
doctors and they paid for his education in exchange.
• Christiaan got his medical training, and then went to the colonies to work as an army
• surgeon
A short time after his arrival he got malaria, and after two years, it became
impossible for him to work. He was sent back home to recover. Back in Europe and
again he went to Berlin in Germany to study the latest groundbreaking medical
research
Christiaan Eijkman was
born on August 11, 1858 in
the Dutch town of Nijkerk.
He was the seventh child of
the headmaster at the local
school.
Robert Koch was Eijkman's teacher in
Berlin in 1885. Twenty years later, Koch was
to receive the Nobel Prize in Physiology or
Medicine for his research
6. • Eijkman had seen many victims of beriberi while working for the army in the
Dutch East Indies.
• The disease started with signs of weakness, fatigue, irritability, restlessness,
loss of appetite and vague abdominal discomfort.
• As it progressed, patients developed burning sensations, tingling in the extremities,
and changes in the sensation such as numbness. Many of the sufferers died of heart
failure.
• Eijkman's Trials; Monkeys, Chickens.
• The man who fed the chickens told Eijkman that he had given them cooked white rice
during the period they got sick. It was leftover rice from the next-door hospital. Later,
a new cook there didn't want to give him left over rice and he had gone back to
feeding them with unpolished uncooked rice. It was after this that the chickens
had recovered.
• When Eijkman understood that the disease had something to do with the diet, he
decided to make trials. He did something like this...
• After five weeks, it was clear to Eijkman that the diet did indeed cause the disease.
He gave all the chickens unpolished uncooked rice, and the four sick chickens
got well again.
7.
8. • He thought that the skin, which had been removed from the white rice, contained
a substance that made the poisonous rice innocuous. Eijkman called this the
anti-beriberi factor.
• Brown rice has its outer husk removed.White rice is polished further to remove
the thin skin and the germ.
• Since the germ is ground off from the white rice grains, they have a slightly
pointed appearance.
• In 1895, after nine years of research with animals, Eijkman wanted to find out if
humans could avoid getting beriberi by eating unpolished rice.
Because it is water soluble, B1 is not stored in the
body and must be supplied daily. Chickpeas, beans,
lentils, brown rice, lean pork and peas are all good
sources of vitamin B1
9. • People found the polished rice from the new milling machines superior in taste, and they chose it over
brown rice even if it was more expensive.
• Christiaan Eijkman was awarded the Nobel Prize in Physiology or Medicine in
1929. Due to bad health, he couldn't come to Sweden to receive the Prize. He
died a year later.
One may wonder why Eijkman was awarded the Prize for the discoved vitamin
B1 even if he himself didn't discover it.
Eijkman was actually awarded the Prize because he was the first to point out a
substance in the rice skin - a substance not to be known as the anti-
beriberifactor as Eijkman called it, but what later was to be known as vitamin B1.
He was also awarded the Prize for his new way of investigating and his methods to
control diseases caused by vitamin deficiency. His trials had become famous.
10. Fortified grain items such as cereals,
bread, pasta, rice and tortillas provide the
most important sources of thiamine in the
human diet. Additionally, lean meats,
fish, sunflower seeds, peas and
legumes are extremely rich in thiamine.
Dairy products, fruits, and vegetables are
typically not ideal sources of vitamin B1
sources of vitaminB1(thiamine)
milk,egg yolks,pork,liver,heart,
kidneys,yeast contamin thiamine as
thiamine pyrophosphate ,broccoli,beans
sweet corn,brown rice.
polished cereals and folur contain
almost no thiamine,
Thermolabile vitamin-- Gets destroyed by
heat in both alkaline and neutral media. Discarding the water in which the food was
cooked also reduces the thiamine content in the cooked food.
11. Dosage Recommendations
The exact amount of vitamin B needed is unknown; however, one
study found that healthy people intake over 9 mg daily. Multivitamin
supplements contain 20-25 mg, which is more than needed by most
people.
(developing chaild in to adult)
12. • Physiological importance (Role) of vitaminB1:
• The active form of vitamin B1 in the body is thiamin pyrophosphate (TPP) which
along with lipoic acid acts as a prosthetic group for carboxylases.
• Thiamine pyrophosphate is formed by the esterification of alcoholic group of
thiamine with phosphate.TPP transferase catalyzes the transfer of pyrophosphate
group from ATP to thiamine.
• Citric acid cycle and synthesis of acetylcholine thus affecting the neurotransmitter
transmission. Transketolation reaction and decarboxylation of α-ketoglutaric acid to
succinic acid.
N
N
CH3
CH2
NH2
S
CH
N
+
CH3
CH2 CH2 O P
OH
O
O P
O
OH
OH
Esterification
ATP AMP
TPP transferase
NH2
Thiamine pyrophosphate
13.
14. • A deficiency in thiamine can cause enlargement of the heart, which can itself lead to
congestive heart failure, and lung congestion. A severe deficiency in Vitamin B1 can lead
to nerve damage, brain damage and even death. Mental symptoms associated with a
serious lack of Vitamin B include fatigue, psychosis, and confusion.
These are a few serious diseases specifically associated with a deficiency of Vitamin B1,
including the notorious beriberi disease. There are also two specific types of brain
damage associated with severely low levels of Vitamin B1. One, Korsakoff syndrome,
results in confusion and short term memory loss. Another, Wernicke’s Disease(impaired
sensoryperception) has symptoms that include vision disturbances and irregularities, an
unsteady walk, and mental confusion.
Symptoms include pain,
numbness and tingling in the
extremities, muscle weakness
and a lack of physical
coordination, particularly in the
larger muscle masses that make
up the leg muscles
edema,(swelling of bodily
tissues)irregular heart beat.
amnesia,confabulation.
Heart failure and death may
occur in advanced cases.
15.
16. • 1.Polyneuritis:
In birds polyneuritis results muscular paralysis which results in an inability
to fly,walk or even stand.
Increased influx of pyruvic acid in the brain due to impaired functioning of the
Blood brain barrier.
2. Beriberi caused due to deficiency of Vitamin B1 --- individuals who consume
polished or refined rice gets beri beri.
Alcoholics -- genarally retards the absorption of the vitamin.
symptoms: weakness irritable nature,depression,drowsiness ,loss of
sleep,appetite ,nausea,abdominal discomfort.
Eventual symptos: peripheral neuritis,cramping of leg muscles ,psychological
distrubances,CHF.
Depending upon the symptoms beriberi it classified in to 4 types.
1.Dry Beriberi: peripherial neuritis,muscular atrophy,numbness,burning sensation
of legs.
wasting of muscles,paralysis in children ,tachycardia.
2.Wet beriberi: vomiting,waxyskin,albuminuria and casts in urine.
3. Acute pernicious beriberi: leasions in cardiac tissue,peripheral nerves and skin
cardiomegaly,edematous legs , finally death results due to cardiac failure.
17. • 4.Wernick's encephalopathy(cerebral Beriberi):
• It occurs due to severe deficiency of thiamine and is manifested by peripheral
neuropathy,mental confusion paralysis of eye muscles,unsteady gait etc.
• The cardiovascular and gastrointestinal symptoms can be ameliorated or rather
reversed with the administration of thiamine.
The reversal of neurological damage becomes very bleak incase of severe or
prolonged deficiency of the thiamine.
Adverse effects:
Using thiamine 5mg day for 4-5 weeks leads to headache,isomnia,
irritability,increased heartrate,weakness, Injections of thiamine lead to anaphylactic
reactions.
Dry Beri-beriWet Beri-beri.
18. Synthesis of vitamin B1
4-amino-5-bromo
methyl-2-methyl
pyrimidine hydro chloride.
5-(β-hydroxyethyl)-4-
methyl thiazole. Bromide salt
Thiamine hydrochloride.
19. K3Fe(CN)6
Oxidation
(Fluorescence)
Thiamine oxidizes to thiochrone in the presence of oxidizing agents like H2O2,
Kmn04 (or) alkaline potassium ferricyanide (or) on exposure to atomsphere.
Thiochrome emits a blue fluorescence.
Excite thiochrome at 365 nm and measure the absorbance at 435 nm
Blue fluorescence
The oxidation of thiamine to thiochrome
20. Thiamin helps break down
sugars, carbohydrates and
fats in the body to provide
energy. Vitamin B1 also helps
support a normal appetite,
maintains a healthy
nervous system as well as
aiding the proper function of
the heart and other muscles.
Vitamin B1 has been used
for conditions including:
Anemia (offers probable
health benefit)
Alzheimer’s Disease
Canker Sores
Hepatitis
Lower back pain
used in the prophylaxis or treatment of diseases
like alcoholic neuritis.
cardiovascular diseases and GIT symptoms.
treatment of Beri-beri.
If breast-fed infant is suffering from beriberi ---
Mother should be given ----50mg daily dose.
infants --- 10 mg.
Therapeutic uses
Required to make energy.
Prevents the disease beri-
beri i.e. nerve damage,
paralysis, heart failure.
Vitamin B1, also called thiamin, is
important to blood circulation,
metabolism, and brain function.
Because of its antioxidant powers.