Transcript QUININE

QUININE
-CHEMISTRY BEHIND THE ANTI-MALARIAL
DRUG
WHAT IS QUININE?
• Natural, white crystalline alkaloid
• Possesses antipyretic, antimalarial , analgesic
and anti-inflammatory properties
• Bitter taste
• Stereoisomer of quinidine
• Possesses 2 major ring systems: aromatic
quinoline , bicyclic quinuclidine.
BIOLOGICAL SOURCES
AND HISTORY
• Cinchona species (Rubiaceae)
• Obtained from cinchona or peruvian bark
• First discovered by Quechua of Peru and
Bolivia
• First used antimalarial drug
CHEMICAL STRUCTURE
(R)-(6-Methoxyquinolin-4-yl)((2S,4S,8R)-8-vinylquinuclidin-2-yl)methanol
CHARACTERISTICS
• Fluoresces in direct sunlight
• Sublimes in vacuum at 443-453k.
• Dissociation constants Pk1=5.07 and
pK2=9.7
• pH of saturated solution=8.8
• Fluoresces with a blue colour especially in
sulphuric acid.
FUNCTIONAL GROUPS
• It's functional groups are:
* alkene
* tertiary amine (the quinuclidine bicyclic system)
* secondary alcohol
* quinoline (an aromatic system, specifically 1azanaphthalene)
* phenolic ether (or perhaps simply an aromatic
ether)
TYPES OF BONDS
PRESENT IN QUININE
• All the bonds present in quinine are covalent bonds.
R AND S FORMS
Powdered Bark
- Alk. CaO + NaOH + H2O
- Reflux with benzene &
- Filtration while hot
Benzene filtrate (Alkaloidal bases)
dilute H2SO4
Acidic aqueous layer (Alkaloidal bisulphates)
pH to 6.5 with Na2CO3
Precipitate
Quinine
(monosulphate)
Hot water, Na2CO3
Aqueous solution (Monosulphates)
quinidine,
cinchonine & cinchonidine
NaOH, ether
Quinine
Ether layer
Quinidine & Cinchonidine
Aqueous layer
-HCl PH=7, Na, K Tart. salt
- filter
Precipitate
Cinchonidine tartrate
Filtrate
Quinidine tartrate
Cinchonine
RABE AND KINDLER
PROCESS
• In 1918 Paul Rabe and Karl Kindler obtained a
three step preparation of quinine from dquinotoxine
IDENTIFICATION TESTS
a)Colour Tests:
1.Oxygenated Acids : Strong, blue fluorescence
in sulphuric acid, acetic acid,etc.
2. Herpathite Test: boiling mixture of
quinine(0.3g)+ 7.5ml glacial acetic acid+ 5
drops of conc. H2SO4 in 3ml
ethanol(0.9v/v)+3.5 ml of I2
solution(0.01w/v) in ethanol—dark crystals
of sulphate of iodoquinine (herpathite)
obtained.
(
(
c) Thalleioquin Test: Br2 water+2-3 ml of
weakly acidic solution of quinine salt+0.5-1 ml
of strong ammonia solution—distinct emerald
green colouration.
(d) Erythroquinine Test(Rosequin Test):
Quinine+ dil. Acetic acid+ freshly prepared Br2
water+ 10% solution of [K4Fe(CN)6]+ conc.
NH4OH soln—red colouration.
USES
• Flavour in carbonated beverages.
• Antimalarial agent.
• Skeletal muscle relaxant.
• Used to treat hemorrhoids and varicose veins
• Oxytocic agent.
• Prophylactic for flu.
DERIVATIVES OF QUININE
1)Quinine Trihydrate
2)Quinine bisulphate heptahydrate
3)Quinine dihydrochloride
4)Quinine hydrochloride dehydrate
5)Quinine sulphate dehydrate
QUININE TRIHYDRATE
• It has a melting point of 330 K
• It becomes anhydrous at 398 K
QUININE BISULPHATE
HEPTAHYDRATE
• It is obtained as bitter crystals
• Also known as Quinbisan, Dentojel.
QUININE
DIHYDROCHLORIDE
• Also known as quinine dichloride, Quinine
bimuriate
• Slightly soluble in chloroform and very
slightly soluble in ether
• Aqueous solutions are found to be higly
acidic with a pH of 2.6
QUININE HYDROCHLORIDE
DIHYDRATE
• Obtained as silky needles of bitter
taste
• It effloresces on exposure to warm
air.
• Forms anhydrous solution at 373 K.
QUININE SULPHATE
DIHYDRATE
• Also known as Quinsan, Quine and
Quinate
• Its is obtained as dull needles or rods
making a light and readily compressible
mass.
• Losses water of crystallization at 383 K.
• Slightly soluble in ether and chloroform
QUININE ISOMER :
QUINIDINE
(S)-(6-Methoxyquinolin-4-yl)((2R,4S,8R)-8-vinylquinuclidin-2-yl)methanol
Powdered Bark
- Alk. CaO + NaOH + H2O
- Reflux with benzene &
- Filtration while hot
Benzene filtrate (Alkaloidal bases)
dilute H2SO4
Acidic aqueous layer (Alkaloidal bisulphates)
pH to 6.5 with Na2CO3
Precipitate
Quinine
(monosulphate)
Hot water, Na2CO3
Aqueous solution (Monosulphates)
quinidine,
cinchonine & cinchonidine
NaOH, ether
Quinine
Ether layer
Quinidine & Cinchonidine
Aqueous layer
-HCl PH=7, Na, K Tart. salt
- filter
Precipitate
Cinchonidine tartrate
Filtrate
Quinidine tartrate
Cinchonine
PROPERTIES
• It is optical isomer of quinine
• It is a diastereomer of quinidine
• It is found as white powder or crystals
• Insoluble in water
• It melts at 441 K
USES
• It is an antiarrhythmic agent
• It helps in keeping the heart rate normal
for the people with certain heart rhythm
disorders.
DONE BY
DHRUVI, RUTVI, SIDDHARTH