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 1- azanaphthalene)* 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

PrecipitateQuinine quinidine,

cinchonine & cinchonidine Hot water, Na2CO3

Quinine NaOH, ether

Aqueous layerEther layer

CinchonineQuinidine & Cinchonidine-HCl PH=7, Na, K Tart. salt- filter

Precipitate Filtrate

Cinchonidine tartrate Quinidine tartrate

Aqueous solution (Monosulphates)(monosulphate)

RABE AND KINDLER PROCESS

• In 1918 Paul Rabe and Karl Kindler obtained a three step preparation of quinine from d- quinotoxine

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 Trihydrate2)Quinine bisulphate heptahydrate3)Quinine dihydrochloride4)Quinine hydrochloride dehydrate5)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

PrecipitateQuinine quinidine,

cinchonine & cinchonidine Hot water, Na2CO3

Quinine NaOH, ether

Aqueous layerEther layer

CinchonineQuinidine & Cinchonidine-HCl PH=7, Na, K Tart. salt- filter

Precipitate Filtrate

Cinchonidine tartrate Quinidine tartrate

Aqueous solution (Monosulphates)(monosulphate)

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.

….THANK YOU….DONE BY DHRUVI, RUTVI, SIDDHARTH