Pharmaceutical chemistry

2. Definitionof Vitamins
The term vitamin refers to an essential
dietary factor that is required by an
organism in small amounts and whose
absence results in deficiency diseases.

3. Classificationof Vitamins
• There are about 25 vitamins which have been
arbitrarily classified into two types:

4. Nicotinicacid(Niacin)
• Niacin (nicotinic acid and the amide derivative nicotinamide)
is one of the water soluble B-vitamins.
• In the blood, brain, kidney and liver it is converted to the
coenzymes nicotinamide adenine dinucleotide (NAD) and
nicotinamide adenine dinucleotide phosphate (NADP), both of
which are involved in the generation of energy in cells.
• Tryptophan is an amino acid which is a provitamin of
niacin.The term niacin is the official name of the vitamin
nicotinic acid.
• The biochemically active form of vitamin niacin is the amide,
nicotinamide or niacinamide .
• Niacin is pyridine derivative (pyridine -3-carboxylic acid)

5. 3
2
4
N
1
5
6
7
O
9
OH
8
Nicotinic Acid [Plant form]
3
2
4
N
1
5
6
7
O
9
NH2
8
Nicotinamide [Animal form]
[reduced form]

6. Physical and Chemicalproperties
Nicotinic acid and nicotinamide are colorless
crystalline substances.
Each is insoluble or only sparingly soluble in organic
solvents. Nicotinic acid is slightly soluble in water and
ethanol. Nicotinamide is very soluble in water and
moderately soluble in ethanol.
The two compounds have similar absorption spectra
in water, with an absorption maximum at ∼262 nm.

7. Chemistry
Nicotinic acid is zwitterionic in nature; at high pH it is negatively
charged at the carboxylic function, while at low pH it is positively
charged at the pyridinyl nitrogen. Thus it is considered an amphoteric
molecule because it forms salts with acids as well as bases
Both nicotinic acid and nicotinamide are very
stable in dry form ; in solution nicotinamide is
hydrolysed by acids and bases to yield nicotinic
acid.

8. Essentialfeaturesof thechemical
structure
• Pyridine nucleus substituted with a β-carboxylic acid
or a corresponding amine.
• Pyridine nitrogen must be able to undergo reversible
oxidation/reduction (quaternary pyridinium ion
to/from tertiary amine).
• Pyridine carbons adjacent to the nuclear nitrogen
atom must be open
pyridinium ion

9. Constitution
• The molecular formula is C6H5NO2
• The formation of salts (monosodium), esters and acid
chlorides indicate the presence of one –COOH group.
• The formation of crystalline hydrochloride shows the
basic nature of the nicotinic acid.
• On distillation with lime, it gives pyridine.
N
O
OH
N
+ CO2
LIME
HEAT

10.  The liver can synthesize niacin from essential aminoacid
tryptophan
 60 mg of tryptophan can form 1mg of niacin.
 Synthesis of niacin from tryptophan also requires
pyridoxine, riboflavin and iron.
Biosynthesisof Niacin

11. Dietary Sources
• Liver
• Lean meat,eggs and dried
yeast
• Unrefined grains
• Cereals
• Milk is poor source, but
has tryptophan.
• Maize has niacin tightly
bound form not available.

12. RDA
The requirement
increases with
increased intake
of calories,illness,
severe
injury,infections,
burns, high corn
diet, pregnancy
and lactation

13. BiochemicalFunctions
A sufficient intake of vitamin B3 (niacin) is important as
it helps the body to
• convert food into glucose
• used to produce energy
• produce macromolecules, including fatty acids and
cholesterol
• DNA repair and stress responses.
• Maintenance of normal skin and mucous membranes

14. Functions
• Niacin is required by all cells.
• It plays a vital role in the release of energy from all
energy yielding nutrients-CHO, fat, protein, alcohol.
• Also required for the synthesis of protien, fat & 5C sugars
needed for the formation of DNA & RNA.
• The biochemical role of niacin is to form part of
coenzymes NAD & NADP require by many of the key
pathways of the metabolism.
• Coenzymes NAD and NADPH are electron carriers of cells.
NAD is primarily involve in catabolic reactions whereas,
NADP functions mainly in anabolic reactions. They are
coenzymes for more than 200 enzymes reactions.

15. Functions
• Some of the reactions where niacin in the form of
NAD is involved are :
1. Conversion of lactate to pyruvate in glycolytic
pathway.
2. Glyceradehyde-3-PO4 to 1, 3 biphosphoglycerate in
glycolytic pathway.
3. In biological oxidation reduction complex.
4. α- ketoglutarate to succinyl CoA in TCA cycle. 5.
Malate to oxaloactetate in TCA cycle

16. Functions
Niacin in the form of NADP is involved in the
following:
1. Glucose-6-PO4 to 6-Phospho gluconolactone in
HMP stunt.
2. 6-phospho gluconate to 3 keto-6 phosphogluconate
in HMP stunt.
Thus they play an important role in mechanisms for
DNA repair and gene stability and therefore
influence cancer risk.

17. Deficiency
• Pellagra – rare in Western societies.
• Nervousness
• irritability
• Fatigue
• Head ache
• Insomnia
• Mental depression

18. Therapeuticuses of niacin
• Niacin is used to (3-6 mg/day) treat
hypercholesterolemia & hypertriacylglyceridemia
• It inhibits flux of FA from adipose tissue, Acetyl CoA is
reduced
• It is also used to elevate plasma HDL levels
• It decreases LDL & VLDL levels
• Decreased activity of hormone sensitive lipase

19. References
• Chemistry of Natural Products: Sujata V. Bhat, B.A.
Nagasampagi, Meenakshi Sivakumar Springer Science
& Business Media, 04-Jan-2005 - Science - 840 pages
• Organic Chemistry Natural Products-Vol- I by O.P.
Agarwal
• B Vitamins and Folate: Chemistry, Analysis, Function
and Effects Edited by Victor R. Preedy ; The Royal
Society of Chemistry 2013 ;Published by the Royal
Society of Chemistry, www.rsc.org